1691:
immunostimulatory. CpG stimulatory (CpG-S) sequences occur twenty times more frequently in bacterially-derived DNA than in eukaryotes. This is because eukaryotes exhibit "CpG suppression" – i.e. CpG dinucleotide pairs occur much less frequently than expected. Additionally, CpG-S sequences are hypomethylated. This occurs frequently in bacterial DNA, while CpG motifs occurring in eukaryotes are methylated at the cytosine nucleotide. In contrast, nucleotide sequences that inhibit the activation of an immune response (termed CpG neutralising, or CpG-N) are over represented in eukaryotic genomes. The optimal immunostimulatory sequence is an unmethylated CpG dinucleotide flanked by two 5’
127:. DNA vaccines contain DNA that codes for specific antigens from a pathogen. The DNA is injected into the body and taken up by cells, whose normal metabolic processes synthesize proteins based on the genetic code in the plasmid that they have taken up. Because these proteins contain regions of amino acid sequences that are characteristic of bacteria or viruses, they are recognized as foreign and when they are processed by the host cells and displayed on their surface, the immune system is alerted, which then triggers immune responses. Alternatively, the DNA may be encapsulated in protein to facilitate cell entry. If this
1682:). However, the potential toxicity of prolonged cytokine expression is not established. In many commercially important animal species, cytokine genes have not been identified and isolated. In addition, various plasmid-encoded cytokines modulate the immune system differently according to the delivery time. For example, some cytokine plasmid DNAs are best delivered after immunogen pDNA, because pre- or co-delivery can decrease specific responses and increase non-specific responses.
39:
1022:
1806:. Unlike conventional DNA vaccinations alphavirus vectors kill transfected cells and are only transiently expressed. Alphavirus replicase genes are expressed in addition to the vaccine insert. It is not clear how alphavirus replicons raise an immune response, but it may be due to the high levels of protein expressed by this vector, replicon-induced cytokine responses, or replicon-induced apoptosis leading to enhanced antigen uptake by dendritic cells.
1753:(PkMSP1p42). They were then boosted with a recombinant canarypox virus encoding all four antigens (ALVAC-4). Immunized monkeys developed antibodies against sporozoites and infected erythrocytes, and IFN-γ-secreting T-cell responses against peptides from PkCSP. Partial protection against sporozoite challenge was achieved, and mean parasitemia was significantly reduced, compared to control monkeys. These models, while not ideal for extrapolation to
1528:
lymph node where they prime secondary B- and T-cell responses. In skeletal muscle, striated muscle cells are most frequently transfected, but seem to be unimportant in immune response. Instead, IM inoculated DNA "washes" into the draining lymph node within minutes, where distal dendritic cells are transfected and then initiate an immune response. Transfected myocytes seem to act as a "reservoir" of antigen for trafficking professional APCs.
662:
5711:
1488:
467:
1638:(PyCSP) enhanced protection against subsequent challenge (whereas plasmid-encoded PyCSP alone did not). It was proposed that GM-CSF caused dendritic cells to present antigen more efficiently and enhance IL-2 production and TH cell activation, thus driving the increased immune response. This can be further enhanced by first priming with a pPyCSP and pGM-CSF mixture, followed by boosting with a recombinant
1232:
1719:
been used as external adjuvants for both DNA and recombinant protein vaccination with variable success rates. Other organisms with hypomethylated CpG motifs have demonstrated the stimulation of polyclonal B-cell expansion. The mechanism behind this may be more complicated than simple methylation – hypomethylated murine DNA has not been found to mount an immune response.
1567:, which do not kill the cell, but limit viral infection by down-regulating the expression of viral components. DNA vaccinations can be used to curb viral infections by non-destructive IFN-mediated control. This was demonstrated for hepatitis B. IFN-γ is critically important in controlling malaria infections and is a consideration for anti-malarial DNA vaccines.
407:
inverted and tandem repeats, which are conspicuous in many commercially available cloning and expression vectors. Therefore, the reduction or complete elimination of extraneous noncoding backbone sequences would pointedly reduce the propensity for such events to take place and consequently the overall plasmid's recombinogenic potential.
1732:
envelope protein. Recombinant virus boosts have been shown to be very efficient at boosting DNA-primed CTL responses. Priming with DNA focuses the immune response on the required immunogen, while boosting with the recombinant virus provides a larger amount of expressed antigen, leading to a large increase in specific CTL responses.
1389:
profile of the immune response and thus the antibody isotype, which is not possible with either natural infection or recombinant protein immunization. Antibody responses generated by DNA are useful as a preparative tool. For example, polyclonal and monoclonal antibodies can be generated for use as reagents.
1550:(FDC), which are potent B-cell stimulators. T-cells can be stimulated by similar, germinal centre dendritic cells. FDC are able to generate an immune memory because antibodies production "overlaps" long-term expression of antigen, allowing antigen-antibody immunocomplexes to form and be displayed by FDC.
995:
The delivery method determines the dose required to raise an effective immune response. Saline injections require variable amounts of DNA, from 10 μg to 1 mg, whereas gene gun deliveries require 100 to 1000 times less. Generally, 0.2 μg – 20 μg are required, although quantities as
1739:
circumsporozoite surface protein (PyCSP), then boosted with a recombinant vaccinia virus expressing the same protein had significantly higher levels of antibody, CTL activity and IFN-γ, and hence higher levels of protection, than mice immunized and boosted with plasmid DNA alone. This can be further
1527:
IM and ID DNA delivery initiate immune responses differently. In the skin, keratinocytes, fibroblasts and
Langerhans cells take up and express antigens and are responsible for inducing a primary antibody response. Transfected Langerhans cells migrate out of the skin (within 12 hours) to the draining
1267:
Comparisons of antibody responses generated by natural (viral) infection, immunization with recombinant protein and immunization with pDNA are summarised in Table 4. DNA-raised antibody responses rise much more slowly than when natural infection or recombinant protein immunization occurs. As many as
1058:
The type of T-cell help raised is influenced by the delivery method and the type of immunogen expressed, as well as the targeting of different lymphoid compartments. Generally, saline needle injections (either IM or ID) tend to induce TH1 responses, while gene gun delivery raises TH2 responses. This
1731:
DNA-primed immune responses can be boosted by the administration of recombinant protein or recombinant poxviruses. "Prime-boost" strategies with recombinant protein have successfully increased both neutralising antibody titre, and antibody avidity and persistence, for weak immunogens, such as HIV-1
1388:
epitopes than recombinant protein-induced antibodies. In other words, DNA immunization induces a qualitatively superior response. Antibodies can be induced after one vaccination with DNA, whereas recombinant protein vaccinations generally require a boost. DNA immunization can be used to bias the TH
1085:
How these different methods operate, the forms of antigen expressed, and the different profiles of T-cell help is not understood. It was thought that the relatively large amounts of DNA used in IM injection were responsible for the induction of TH1 responses. However, evidence shows no dose-related
1722:
Most of the evidence for immunostimulatory CpG sequences comes from murine studies. Extrapolation of this data to other species requires caution – individual species may require different flanking sequences, as binding specificities of scavenger receptors vary across species. Additionally, species
1718:
Manipulation of CpG-S and CpG-N sequences in the plasmid backbone of DNA vaccines can ensure the success of the immune response to the encoded antigen and drive the immune response toward a TH1 phenotype. This is useful if a pathogen requires a TH response for protection. CpG-S sequences have also
1580:
An effective vaccine must induce an appropriate immune response for a given pathogen. DNA vaccines can polarise T-cell help towards TH1 or TH2 profiles and generate CTL and/or antibody when required. This can be accomplished by modifications to the form of antigen expressed (i.e. intracellular vs.
1518:
Besides direct transfection of dendritic cells or macrophages, cross priming occurs following IM, ID and gene gun DNA deliveries. Cross-priming occurs when a bone marrow-derived cell presents peptides from proteins synthesised in another cell in the context of MHC class 1. This can prime cytotoxic
1025:
Antigen presentation stimulates T cells to become either "cytotoxic" CD8+ cells or "helper" CD4+ cells. Cytotoxic cells directly attack other cells carrying certain foreign or abnormal molecules on their surfaces. Helper T cells, or Th cells, coordinate immune responses by communicating with other
415:
Once the plasmid inserts itself into the transfected cell nucleus, it codes for a peptide string of a foreign antigen. On its surface the cell displays the foreign antigen with both histocompatibility complex (MHC) classes I and class II molecules. The antigen-presenting cell then travels to the
1272:
DNA vaccine expressing HBV small and middle envelope protein was injected into adults with chronic hepatitis. The vaccine resulted in specific interferon gamma cell production. Also specific T-cells for middle envelop proteins antigens were developed. The immune response of the patients was not
406:
Structural instability phenomena are of particular concern for plasmid manufacture, DNA vaccination and gene therapy. Accessory regions pertaining to the plasmid backbone may engage in a wide range of structural instability phenomena. Well-known catalysts of genetic instability include direct,
1752:
were primed with a multicomponent, multistage DNA vaccine encoding two liver-stage antigens – the circumsporozoite surface protein (PkCSP) and sporozoite surface protein 2 (PkSSP2) – and two blood stage antigens – the apical merozoite surface protein 1 (PkAMA1) and merozoite surface protein 1
1690:
Plasmid DNA itself appears to have an adjuvant effect on the immune system. Bacterially derived DNA can trigger innate immune defence mechanisms, the activation of dendritic cells and the production of TH1 cytokines. This is due to recognition of certain CpG dinucleotide sequences that are
632:
immunization (ELI). Using this technique, potentially all the genes from a pathogen can be delivered at one time, which may be useful for pathogens that are difficult to attenuate or culture. ELI can be used to identify which genes induce a protective response. This has been tested with
88:
use. In some cases, protection from disease in animals has been obtained, in others not. Research is ongoing over the approach for viral, bacterial and parasitic diseases in humans, as well as for cancers. In August 2021, Indian authorities gave emergency approval to
186:
began tests of a different DNA vaccine against Zika in Miami. The NIH vaccine is injected into the upper arm under high pressure. Manufacturing the vaccines in volume remained unsolved as of August 2016. Clinical trials for DNA vaccines to prevent HIV are underway.
1615:, and GM-CSF) plus TH2-inducing cytokines increase antibody responses, whereas pro-inflammatory agents and TH1-inducing cytokines decrease humoral responses and increase cytotoxic responses (more important in viral protection). Co-stimulatory molecules such as
1710:
The innate system works with the adaptive immune system to mount a response against the DNA encoded protein. CpG-S sequences induce polyclonal B-cell activation and the upregulation of cytokine expression and secretion. Stimulated macrophages secrete IL-12,
1239:
Antibody responses elicited by DNA vaccinations are influenced by multiple variables, including antigen type; antigen location (i.e. intracellular vs. secreted); number, frequency and immunization dose; site and method of antigen delivery.
1778:) with DNA. Such DNA-coated microparticles can be as effective at raising CTL as recombinant viruses, especially when mixed with alum. Particles 300 nm in diameter appear to be most efficient for uptake by antigen presenting cells.
2727:
Böhm W, Kuhröber A, Paier T, Mertens T, Reimann J, Schirmbeck R (June 1996). "DNA vector constructs that prime hepatitis B surface antigen-specific cytotoxic T lymphocyte and antibody responses in mice after intramuscular injection".
206:
As of 2021 no DNA vaccines have been approved for human use in the United States. Few experimental trials have evoked a response strong enough to protect against disease and the technique's usefulness remains to be proven in humans.
3205:"Genetic immunization of BALB/c mice with a plasmid bearing the gene coding for a hybrid merozoite surface protein 1-hepatitis B virus surface protein fusion protects mice against lethal Plasmodium chabaudi chabaudi PC1 infection"
1062:
Generally the type of T-cell help raised is stable over time, and does not change when challenged or after subsequent immunizations that would normally have raised the opposite type of response in a naïve specimen. However, Mor
1459:
The 30kDa surface receptor binds specifically to 4500-bp DNA fragments (which are then internalised) and is found on professional APCs and T-cells. Macrophage scavenger receptors bind to a variety of macromolecules, including
4431:
Wolff JA, Dowty ME, Jiao S, Repetto G, Berg RK, Ludtke JJ, et al. (December 1992). "Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscle".
1790:
have been used to improve DNA vaccination efficiency. The gene encoding the antigen of interest is inserted into the alphavirus replicon, replacing structural genes but leaving non-structural replicase genes intact. The
1558:
Both helper and cytotoxic T-cells can control viral infections by secreting interferons. Cytotoxic T cells usually kill virally infected cells. However, they can also be stimulated to secrete antiviral cytokines such as
1383:
Additionally, the titres of specific antibodies raised by DNA vaccination are lower than those obtained after vaccination with a recombinant protein. However, DNA immunization-induced antibodies show greater affinity to
2178:
White LO, Gibb E, Newham HC, Richardson MD, Warren RC (July 1979). "Comparison of the growth of virulent and attenuated strains of
Candida albicans in the kidneys of normal and cortison-treated mice by chitin assay".
2224:"Construction of live vaccines using genetically engineered poxviruses: biological activity of vaccinia virus recombinants expressing the hepatitis B virus surface antigen and the herpes simplex virus glycoprotein D"
518:. Immune responses to this method can be affected by factors including needle type, needle alignment, speed of injection, volume of injection, muscle type, and age, sex and physiological condition of the recipient.
1268:
12 weeks may be required to reach peak titres in mice, although boosting can decrease the interval. This response is probably due to the low levels of antigen expressed over several weeks, which supports both
1479:, and other delivery methods bypass this entry method, but understanding it may be useful in reducing costs (e.g. by reducing the requirement for cytofectins), which could be important in animal husbandry.
348: – is the "vehicle" from which the immunogen is expressed, optimising vector design for maximal protein expression is essential. One way of enhancing protein expression is by optimising the
1126:. In autoimmune diseases, the goal is to shift the self-destructive TH1 response (with its associated cytotoxic T cell activity) to a non-destructive TH2 response. This has been successfully applied in
170:
demonstrated that direct injection of mice with plasmid DNA encoding a flu antigen protected the animals against subsequent experimental infection with influenza virus. In 2016 a DNA vaccine for the
3157:
Huebener N, Fest S, Strandsby A, Michalsky E, Preissner R, Zeng Y, et al. (July 2008). "A rationally designed tyrosine hydroxylase DNA vaccine induces specific antineuroblastoma immunity".
2680:"Immune responses induced by intramuscular or gene gun injection of protective deoxyribonucleic acid vaccines that express the circumsporozoite protein from Plasmodium berghei malaria parasites"
1038:
profiles. A major advantage of DNA vaccines is the ease with which they can be manipulated to bias the type of T-cell help towards a TH1 or TH2 response. Each type has distinctive patterns of
84:. DNA vaccines have theoretical advantages over conventional vaccines, including the "ability to induce a wider range of types of immune response". Several DNA vaccines have been tested for
1000:. Saline injections require more DNA because the DNA is delivered to the extracellular spaces of the target tissue (normally muscle), where it has to overcome physical barriers (such as the
3110:"Targeting of HIV-1 antigens for rapid intracellular degradation enhances cytotoxic T lymphocyte (CTL) recognition and the induction of de novo CTL responses in vivo after immunization"
1195:
proteins, but the principle should also be applicable to DNA vaccines. Targeting antigens for intracellular degradation (and thus entry into the MHC class I pathway) by the addition of
2290:
Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, et al. (March 1993). "Heterologous protection against influenza by injection of DNA encoding a viral protein".
454:
of the protein can also affect antibody responses. "Ordered" structures (such as viral particles) are more effective than unordered structures. Strings of minigenes (or MHC class I
3875:"Characterization of humoral and CD4+ cellular responses after genetic immunization with retroviral vectors expressing different forms of the hepatitis B virus core and e antigens"
3289:
1581:
secreted), the method and route of delivery or the dose. It can also be accomplished by the co-administration of plasmid DNA encoding immune regulatory molecules, i.e. cytokines,
5121:"Improving protective immunity induced by DNA-based immunization: priming with antigen and GM-CSF-encoding plasmid DNA and boosting with antigen-expressing recombinant poxvirus"
5069:"Genetic vaccination against malaria infection by intradermal and epidermal injections of a plasmid containing the gene encoding the Plasmodium berghei circumsporozoite protein"
1515:
to present antigens. After IM and ID injections, dendritic cells present antigen in the draining lymph node and transfected macrophages have been found in the peripheral blood.
399:
tripartite leader (TPL) sequences and modifications to the polyadenylation and transcriptional termination sequences. An example of DNA vaccine plasmid is pVAC, which uses SV40
1026:
cells. In most cases, T cells only recognize an antigen if it is carried on the surface of a cell by one of the body's own MHC, or major histocompatibility complex, molecules.
213:
DNA immunization is also being investigated as a means of developing antivenom sera. DNA immunization can be used as a technology platform for monoclonal antibody induction.
1740:
enhanced by priming with a mixture of plasmids encoding PyCSP and murine GM-CSF, before boosting with recombinant vaccinia virus. An effective prime-boost strategy for the
3981:"Activation of cutaneous dendritic cells by CpG-containing oligodeoxynucleotides: a role for dendritic cells in the augmentation of Th1 responses by immunostimulatory DNA"
1634:. Plasmid encoding B7-1 (a ligand on APCs) successfully enhanced the immune response in tumour models. Mixing plasmids encoding GM-CSF and the circumsporozoite protein of
1059:
is true for intracellular and plasma membrane-bound antigens, but not for secreted antigens, which seem to generate TH2 responses, regardless of the method of delivery.
1651:
1 (C-terminus)-hepatitis B virus surface protein (PcMSP1-HBs) abolished protection against challenge, compared to protection acquired by delivery of pPcMSP1-HBs alone.
1223:. Co-inoculation with plasmids encoding co-stimulatory molecules IL-12 and TCA3 were shown to increase CTL activity against HIV-1 and influenza nucleoprotein antigens.
5016:
Sato Y, Roman M, Tighe H, Lee D, Corr M, Nguyen MD, et al. (July 1996). "Immunostimulatory DNA sequences necessary for effective intradermal gene immunization".
2001:
4095:"Protective cellular immunity: cytotoxic T-lymphocyte responses against dominant and recessive epitopes of influenza virus nucleoprotein induced by DNA immunization"
341:
vectors (with multiple genes of interest) are sometimes constructed to express more than one immunogen, or to express an immunogen and an immunostimulatory protein.
210:
A veterinary DNA vaccine to protect horses from West Nile virus has been approved. Another West Nile virus vaccine has been tested successfully on
American robins.
3253:
1248:
Humoral responses after a single DNA injection can be much longer-lived than after a single injection with a recombinant protein. Antibody responses against
383:(RSV) promoter had much higher expression rates. More recently, expression and immunogenicity have been further increased in model systems by the use of the
5212:
Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, et al. (April 1995). "CpG motifs in bacterial DNA trigger direct B-cell activation".
4393:
Mancini-Bourgine M, Fontaine H, Bréchot C, Pol S, Michel ML (May 2006). "Immunogenicity of a hepatitis B DNA vaccine administered to chronic HBV carriers".
1735:
Prime-boost strategies have been successful in inducing protection against malarial challenge in a number of studies. Primed mice with plasmid DNA encoding
2411:"A West Nile virus DNA vaccine utilizing a modified promoter induces neutralizing antibody in younger and older healthy adults in a phase I clinical trial"
1252:
virus (HBV) envelope protein (HBsAg) have been sustained for up to 74 weeks without boost, while lifelong maintenance of protective response to influenza
3058:"DNA immunization: ubiquitination of a viral protein enhances cytotoxic T-lymphocyte induction and antiviral protection but abrogates antibody induction"
2937:
Oliveira PH, Prather KJ, Prazeres DM, Monteiro GA (September 2009). "Structural instability of plasmid biopharmaceuticals: challenges and implications".
5779:
6829:
966:
Intranasally delivered liposome-DNA complexes can result in expression in distal mucosa as well as nasal muscosa and the generation of IgA antibodies
4515:"Antigen presentation by dendritic cells after immunization with DNA encoding a major histocompatibility complex class II-restricted viral epitope"
4923:"IL-12 and NK cells are required for antigen-specific adaptive immunity against malaria initiated by CD8+ T cells in the Plasmodium yoelii model"
1770:
The efficiency of DNA immunization can be improved by stabilising DNA against degradation, and increasing the efficiency of delivery of DNA into
4714:"Specific immune induction following DNA-based immunization through in vivo transfection and activation of macrophages/antigen-presenting cells"
1537:
5977:
4302:"Enhancement of cell-mediated immunity against HIV-1 induced by coinnoculation of plasmid-encoded HIV-1 antigen with plasmid expressing IL-12"
3826:"Role of different lymphoid tissues in the initiation and maintenance of DNA-raised antibody responses to the influenza virus H1 glycoprotein"
3408:"Induction of CD8+ T cell responses to dominant and subdominant epitopes and protective immunity to Sendai virus infection by DNA vaccination"
5866:
1179:
molecules. These peptides are derived from cytosolic proteins that are degraded and delivered to the nascent MHC class I molecule within the
474:
DNA vaccines have been introduced into animal tissues by multiple methods. In 1999, the two most popular approaches were injection of DNA in
2334:
6017:
6012:
3455:
Lode HN, Huebener N, Zeng Y, Fest S, Weixler S, Gaedicke G (December 2004). "DNA minigene vaccination for adjuvant neuroblastoma therapy".
4972:"Immunization with plasmid DNA encoding for the measles virus hemagglutinin and nucleoprotein leads to humoral and cell-mediated immunity"
2631:"Complexity of the cytokine and antibody response elicited by immunizing mice with Plasmodium yoelii circumsporozoite protein plasmid DNA"
5659:"Multistage multiantigen heterologous prime boost vaccine for Plasmodium knowlesi malaria provides partial protection in rhesus macaques"
2579:"Intranasal administration of plasmid DNA nanoparticles yields successful transfection and expression of a reporter protein in rat brain"
4467:
Anderson RG, Kamen BA, Rothberg KG, Lacey SW (January 1992). "Potocytosis: sequestration and transport of small molecules by caveolae".
612:
inner core and poly(beta-amino ester) outer coat function synergistically to increase efficiency by addressing barriers associated with
2898:"Novel engineered HIV-1 East African Clade-A gp160 plasmid construct induces strong humoral and cell-mediated immune responses in vivo"
996:
low as 16 ng have been reported. These quantities vary by species. Mice for example, require approximately 10 times less DNA than
1008:) before it is taken up by the cells, while gene gun deliveries drive/force DNA directly into the cells, resulting in less "wastage".
842:
IM; IV (to transfect tissues systemically); intraperitoneal; oral immunization to the intestinal mucosa; nasal/lung mucosal membranes
115:
from a pathogen, or attenuated viruses which stimulate an immune response in the vaccinated organism. DNA vaccines are members of the
2972:
Oliveira PH, Mairhofer J (September 2013). "Marker-free plasmids for biotechnological applications - implications and perspectives".
4253:"A plasmid encoding murine granulocyte-macrophage colony-stimulating factor increases protection conferred by a malaria DNA vaccine"
1499:
mice have shown that antigen is presented by bone-marrow derived cells, which include dendritic cells, macrophages and specialised
568:, and topical administration of pDNA to the eye and vaginal mucosa. Mucosal surface delivery has also been achieved using cationic
1774:. This has been demonstrated by coating biodegradable cationic microparticles (such as poly(lactide-co-glycolide) formulated with
6409:
260:
expression ensures protein more closely resembles normal eukaryotic structure, with accompanying post-translational modifications
6198:
2053:
Alarcon JB, Waine GW, McManus DP (1999). "DNA Vaccines: Technology and
Application as Anti-parasite and Anti-microbial Agents".
1541:
6027:
4033:"Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization"
276:
Potential when using nasal spray administration of plasmid DNA nanoparticles to transfect non-target cells, such as brain cells
5376:"CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma"
416:
lymph nodes and presents the antigen peptide and costimulatory molecule signalling to T-cell, initiating the immune response.
6880:
6808:
2803:
1277:
Table 4. Comparison of T-dependent antibody responses raise by DNA immunisations, protein inoculations and viral infections
458:) from different pathogens raise cytotoxic T-cell responses to some pathogens, especially if a TH epitope is also included.
6414:
424:
Immunogens can be targeted to various cellular compartments to improve antibody or cytotoxic T-cell responses. Secreted or
6446:
6203:
6129:
5982:
131:
protein is included in the DNA, the resulting vaccine can combine the potency of a live vaccine without reversion risks.
5809:
4567:"DNA binding to human leukocytes. Evidence for a receptor-mediated association, internalization, and degradation of DNA"
6856:
6168:
5801:
6268:
2154:
2070:
709:
620:
escape and intracellular cargo concentration. Tested in mice, the hybrid vector was found to induce immune response.
80:(s) against which an immune response is sought, so the cells directly produce the antigen, thus causing a protective
4354:"Long-term maintenance of B cell immunity to influenza virus hemagglutinin in mice following DNA-based immunization"
691:
6949:
6897:
6835:
5810:
1654:
The advantages of genetic adjuvants are their low cost and simple administration, as well as avoidance of unstable
437:
251:
Obviates need for peptide synthesis, expression and purification of recombinant proteins and use of toxic adjuvants
2849:"Increased immune response elicited by DNA vaccination with a synthetic gp120 sequence with optimized codon usage"
6456:
6424:
6419:
6253:
17:
5435:"IFN-gamma promotes IL-6 and IgM secretion in response to CpG motifs in bacterial DNA and oligodeoxynucleotides"
5162:"Augmentation and suppression of immune responses to an HIV-1 DNA vaccine by plasmid cytokine/Ig administration"
4864:"DNA-mediated immunization in a transgenic mouse model of the hepatitis B surface antigen chronic carrier state"
1642:
expressing PyCSP. However, co-injection of plasmids encoding GM-CSF (or IFN-γ, or IL-2) and a fusion protein of
1110:(IL-12) production, while the gene gun bombards the DNA directly into the cell, thus bypassing TH1 stimulation.
6934:
6514:
6124:
687:
1723:
such as ruminants may be insensitive to immunostimulatory sequences due to their large gastrointestinal load.
391:. Additional modifications to improve expression rates include the insertion of enhancer sequences, synthetic
6312:
6022:
5541:"Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA plus protein vaccination"
175:
139:
5600:"Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine"
3356:"Suppression of ongoing ocular inflammatory disease by topical administration of plasmid DNA encoding IL-10"
1183:(ER). Targeting gene products directly to the ER (by the addition of an ER insertion signal sequence at the
4616:"The production and characterization of murine monoclonal antibodies to a DNA receptor on human leukocytes"
683:
270:
Limited to protein immunogens (not useful for non-protein based antigens such as bacterial polysaccharides)
4203:"Enhanced CTL responses mediated by plasmid DNA immunogens encoding costimulatory molecules and cytokines"
2785:
436:
responses can be improved by targeting antigens for cytoplasmic degradation and subsequent entry into the
1564:
6434:
5876:
5859:
3770:"Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization"
1547:
4815:"Pathogenetic effector function of CD4-positive T helper 1 cells in hepatitis B virus transgenic mice"
1546:
DNA vaccination generates an effective immune memory via the display of antigen-antibody complexes on
6484:
1164:. This may prove to be a useful tool in assessing CTL epitopes and their role in providing immunity.
1157:
1153:
767:
4765:
2833:
1410:
cells, these cells were thought to be unique because of their extensive network of T-tubules. Using
1086:
differences in TH type. The type of T-cell help raised is determined by the differentiated state of
6439:
6404:
6399:
6394:
1504:
1152:(CTL) without the inherent risk associated with live vaccines. CTL responses can be raised against
1087:
672:
302:
5067:
Weiss R, Leitner WW, Scheiblhofer S, Chen D, Bernhaupt A, Mostböck S, et al. (October 2000).
3584:
Jones CH, Ravikrishnan A, Chen M, Reddinger R, Kamal Ahmadi M, Rane S, et al. (August 2014).
119:, because they contain a genetic information (DNA or RNA) that codes for the cellular production (
6885:
6818:
6799:
6595:
6567:
6529:
6524:
6504:
6032:
5539:
Letvin NL, Montefiori DC, Yasutomi Y, Perry HC, Davies ME, Lekutis C, et al. (August 1997).
1771:
1675:
1648:
1067:. (1995) immunized and boosted mice with pDNA encoding the circumsporozoite protein of the mouse
751:
676:
613:
5736:
Hooper JW, Thompson E, Wilhelmsen C, Zimmerman M, Ichou MA, Steffen SE, et al. (May 2004).
4766:"Differential dependence on target site tissue for gene gun and intramuscular DNA immunizations"
4251:
Weiss WR, Ishii KJ, Hedstrom RC, Sedegah M, Ichino M, Barnhart K, et al. (September 1998).
1418:(or, non-clathrin coated pits). However, subsequent research revealed that other cells (such as
1256:
was demonstrated in mice after gene gun delivery. Antibody-secreting cells (ASC) migrate to the
1202:, or mutation of other signal sequences, was shown to be effective at increasing CTL responses.
6939:
6866:
6795:
5794:
2512:"Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein"
1099:
1047:
388:
179:
81:
70:
5720:
5160:
Barouch DH, Santra S, Steenbeke TD, Zheng XX, Perry HC, Davies ME, et al. (August 1998).
2896:
Muthumani K, Zhang D, Dayes NS, Hwang DS, Calarota SA, Choo AY, et al. (September 2003).
293:
DNA vaccines elicit the best immune response when high-expression vectors are used. These are
6924:
6861:
6695:
6690:
6146:
6092:
6002:
1612:
1464:
and are thus candidates for DNA uptake. Receptor-mediated DNA uptake could be facilitated by
1180:
755:
594:
vectors for oral administration to the intestinal mucosa and recombinant adenovirus vectors.
344:
Because the plasmid – carrying relatively small genetic code up to about 200 K
306:
5484:"B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation"
4147:
Restifo NP, Bacík I, Irvine KR, Yewdell JW, McCabe BJ, Anderson RW, et al. (May 1995).
2678:
Leitner WW, Seguin MC, Ballou WR, Seitz JP, Schultz AM, Sheehy MJ, Lyon JA (December 1997).
2280:
US Patent 4722848 - Method for immunizing animals with synthetically modified vaccinia virus
1077:(PyCSP) and found that the initial TH2 response changed, after boosting, to a TH1 response.
6744:
6685:
6476:
6119:
5997:
5948:
5915:
5849:
5611:
5552:
5495:
5482:
Barwick BG, Scharer CD, Martinez RJ, Price MJ, Wein AN, Haines RR, et al. (May 2018).
5387:
5325:
5221:
5025:
4875:
4713:
4614:
Bennet RM, Hefeneider SH, Bakke A, Merritt M, Smith CA, Mourich D, Heinrich MC (May 1988).
4476:
4202:
4044:
3934:
3713:
3656:
3597:
3519:
3464:
3265:
2679:
2629:
Mor G, Klinman DM, Shapiro S, Hagiwara E, Sedegah M, Norman JA, et al. (August 1995).
2523:
2299:
2235:
1796:
1787:
1655:
1130:
451:
155:
120:
5264:
5161:
5119:
Sedegah M, Weiss W, Sacci JB, Charoenvit Y, Hedstrom R, Gowda K, et al. (June 2000).
4814:
4615:
4301:
4252:
4148:
3980:
3769:
3702:"DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations"
3407:
3355:
2630:
1187:) should thus enhance CTL responses. This was successfully demonstrated using recombinant
178:. The study was planned to involve up to 120 subjects aged between 18 and 35. Separately,
8:
6667:
6633:
6519:
6342:
6285:
6280:
6231:
6062:
5930:
5902:
5854:
5657:
Rogers WO, Baird JK, Kumar A, Tine JA, Weiss W, Aguiar JC, et al. (September 2001).
5434:
4970:
Cardoso AI, Blixenkrone-Moller M, Fayolle J, Liu M, Buckland R, Wild TF (November 1996).
4922:
1932:
1803:
1775:
1644:
1411:
1123:
763:
759:
298:
85:
6337:
6082:
5716:
5615:
5556:
5499:
5391:
5329:
5312:
Krieg AM, Wu T, Weeratna R, Efler SM, Love-Homan L, Yang L, et al. (October 1998).
5225:
5029:
4879:
4480:
4048:
3938:
3717:
3660:
3601:
3562:
3523:
3468:
3310:
Widera G, Austin M, Rabussay D, Goldbeck C, Barnett SW, Chen M, et al. (May 2000).
3269:
2527:
2303:
2239:
279:
Cross-contamination when manufacturing different types of live vaccines in same facility
6700:
6534:
6275:
6241:
6226:
6102:
6087:
6072:
5992:
5910:
5516:
5483:
5464:
5294:
5245:
5191:
5049:
4952:
4844:
4795:
4743:
4689:
4664:
4645:
4539:
4514:
4331:
4282:
4230:
4173:
4010:
3958:
3922:
3799:
3682:
3620:
3585:
3543:
3488:
3437:
3385:
3182:
3134:
3109:
3033:
3008:
2821:
2709:
2660:
2608:
2541:
2484:
2459:
2435:
2410:
2383:
2356:
2204:
1975:
1950:
1904:
1879:
1715:, TNF-α, IFN-α, IFN-β and IFN-γ, while stimulated B-cells secrete IL-6 and some IL-12.
1496:
1476:
629:
400:
380:
372:
326:
314:
5762:
5737:
5093:
5068:
4591:
4566:
4119:
4094:
3899:
3874:
3850:
3825:
3277:
3229:
3204:
3082:
3057:
2914:
2897:
2873:
2848:
2795:
2577:
Harmon BT, Aly AE, Padegimas L, Sesenoglu-Laird O, Cooper MJ, Waszczak BL (May 2014).
2258:
2223:
2146:
2062:
1205:
CTL responses can be enhanced by co-inoculation with co-stimulatory molecules such as
6944:
6823:
6790:
6623:
6464:
6354:
6248:
6109:
5934:
5897:
5787:
5767:
5688:
5683:
5658:
5639:
5634:
5599:
5580:
5575:
5540:
5521:
5456:
5415:
5410:
5375:
5353:
5348:
5314:"Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs"
5313:
5286:
5237:
5183:
5142:
5098:
5084:
5041:
4993:
4944:
4903:
4898:
4863:
4836:
4787:
4735:
4694:
4637:
4596:
4544:
4492:
4449:
4410:
4375:
4323:
4300:
Tsuji T, Hamajima K, Fukushima J, Xin KQ, Ishii N, Aoki I, et al. (April 1997).
4274:
4222:
4178:
4124:
4072:
4067:
4032:
4002:
3950:
3904:
3873:
Sällberg M, Townsend K, Chen M, O'Dea J, Banks T, Jolly DJ, et al. (July 1997).
3855:
3841:
3791:
3741:
3736:
3701:
3700:
Fynan EF, Webster RG, Fuller DH, Haynes JR, Santoro JC, Robinson HL (December 1993).
3674:
3625:
3535:
3480:
3429:
3377:
3333:
3281:
3234:
3220:
3174:
3139:
3087:
3073:
3038:
2989:
2954:
2919:
2878:
2809:
2799:
2745:
2741:
2701:
2652:
2600:
2559:
2554:
2511:
2489:
2440:
2388:
2315:
2263:
2196:
2160:
2150:
2076:
2066:
1980:
1909:
1853:
1663:
1593:
mixture of 2 plasmids, one encoding the immunogen and the other encoding the cytokine
1219:
1073:
1005:
648:. Even partial expression libraries can induce protection from subsequent challenge.
475:
310:
191:
94:
6769:
5753:
5674:
5598:
Sedegah M, Jones TR, Kaur M, Hedstrom R, Hobart P, Tine JA, Hoffman SL (June 1998).
5468:
5298:
5195:
4956:
4848:
4799:
4747:
4649:
4335:
4286:
4234:
4110:
4014:
3890:
3803:
3547:
3492:
3389:
3186:
2864:
2713:
2664:
2208:
963:
Intravenously delivered liposome-DNA complexes can potentially transfect all tissues
852:
Table 3. Advantages and disadvantages of commonly used DNA vaccine delivery methods
190:
In August 2021, Indian authorities gave emergency approval to ZyCoV-D. Developed by
66:
sequence into the cells of an organism as a mechanism to induce an immune response.
6749:
6734:
6590:
6451:
6364:
5757:
5749:
5678:
5670:
5629:
5619:
5570:
5560:
5511:
5503:
5446:
5405:
5395:
5343:
5333:
5276:
5249:
5229:
5173:
5132:
5088:
5080:
5053:
5033:
4983:
4934:
4893:
4883:
4862:
Mancini M, Hadchouel M, Davis HL, Whalen RG, Tiollais P, Michel ML (October 1996).
4826:
4777:
4725:
4684:
4676:
4627:
4586:
4578:
4534:
4526:
4484:
4441:
4402:
4365:
4313:
4264:
4214:
4168:
4160:
4114:
4106:
4062:
4052:
3992:
3962:
3942:
3894:
3886:
3845:
3837:
3781:
3731:
3721:
3686:
3664:
3615:
3605:
3586:"Hybrid biosynthetic gene therapy vector development and dual engineering capacity"
3527:
3472:
3441:
3419:
3367:
3323:
3273:
3224:
3216:
3166:
3129:
3121:
3077:
3069:
3028:
3020:
2981:
2946:
2909:
2868:
2860:
2791:
2737:
2691:
2642:
2612:
2590:
2549:
2531:
2479:
2471:
2430:
2422:
2406:
2378:
2368:
2307:
2253:
2243:
2188:
2142:
2058:
1970:
1962:
1899:
1891:
1560:
1430:
1149:
433:
147:
6290:
4406:
3170:
2985:
2950:
529:
delivery ballistically accelerates plasmid DNA (pDNA) that has been absorbed onto
482:
delivery. Several other techniques have been documented in the intervening years.
379:
promoter was conventionally used until research showed that vectors driven by the
150:
into vaccines that may be able to prevent other diseases. They altered the DNA of
6754:
6552:
6359:
6317:
6208:
6188:
6158:
6141:
6067:
6057:
5987:
5926:
5922:
5871:
5137:
5120:
5037:
4782:
4730:
4218:
3531:
2696:
2460:"DNA vaccination of American robins (Turdus migratorius) against West Nile virus"
1508:
1461:
1449:
1091:
1043:
499:
491:
425:
384:
322:
143:
116:
5281:
5178:
4831:
4632:
4318:
4269:
4164:
3997:
3786:
3424:
3372:
3328:
3311:
2647:
1264:
for long-term antibody production, and generally localise there after one year.
1140:
and is somewhat successful in shifting the response for an established disease.
498:(ID), delivering DNA to extracellular spaces. This can be assisted either 1) by
321:
stability and hence increase protein expression. Plasmids also include a strong
6891:
6618:
6509:
6469:
6349:
6175:
6114:
5604:
Proceedings of the
National Academy of Sciences of the United States of America
5545:
Proceedings of the
National Academy of Sciences of the United States of America
5507:
5451:
5380:
Proceedings of the
National Academy of Sciences of the United States of America
5318:
Proceedings of the
National Academy of Sciences of the United States of America
4939:
4868:
Proceedings of the
National Academy of Sciences of the United States of America
4037:
Proceedings of the
National Academy of Sciences of the United States of America
3706:
Proceedings of the National Academy of Sciences of the United States of America
3645:"Protection against mycoplasma infection using expression-library immunization"
3590:
Proceedings of the National Academy of Sciences of the United States of America
2516:
Proceedings of the National Academy of Sciences of the United States of America
2228:
Proceedings of the National Academy of Sciences of the United States of America
1749:
1631:
1600:
1519:
T-cell responses and seems to be important for a full primary immune response.
1253:
1199:
1137:
330:
167:
3312:"Increased DNA vaccine delivery and immunogenicity by electroporation in vivo"
2409:, Pierson TC, Hubka SA, Desai N, Rucker S, Gordon IJ, et al. (May 2011).
6918:
6774:
6759:
6729:
6724:
6579:
6332:
6327:
6236:
5881:
5338:
4888:
3726:
3508:"Attenuated Shigella as a DNA delivery vehicle for DNA-mediated immunization"
1966:
1880:"DNA immunization as a technology platform for monoclonal antibody induction"
1792:
1419:
787:(abdominal skin); vaginal mucosa; surgically exposed muscle and other organs
573:
361:
334:
135:
6136:
5624:
5565:
4488:
4057:
4031:
Raz E, Tighe H, Sato Y, Corr M, Dudler JA, Roman M, et al. (May 1996).
3610:
3476:
2536:
2426:
2373:
2311:
2222:
Paoletti E, Lipinskas BR, Samsonoff C, Mercer S, Panicali D (January 1984).
1034:
responses, including lymphoproliferation and the generation of a variety of
6929:
6851:
6494:
6389:
6322:
6263:
5943:
5834:
5814:
5771:
5692:
5525:
5400:
5146:
5102:
4988:
4971:
4948:
4680:
4530:
4445:
4414:
4370:
4353:
3925:, Steinman RM (March 1998). "Dendritic cells and the control of immunity".
3629:
3484:
3337:
3285:
3238:
3178:
3042:
2993:
2958:
2923:
2813:
2604:
2493:
2444:
2392:
2164:
2080:
1984:
1913:
1830:
1825:
1608:
1441:
1385:
1106:
into the dendritic cell, which is then stimulated to differentiate for TH1
1001:
617:
365:
230:
55:
33:
5738:"Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox"
5643:
5584:
5460:
5419:
5357:
5290:
5241:
5187:
5045:
4997:
4907:
4840:
4791:
4739:
4698:
4641:
4600:
4548:
4496:
4453:
4379:
4327:
4278:
4226:
4182:
4128:
4076:
4006:
3954:
3908:
3859:
3795:
3745:
3678:
3539:
3433:
3381:
3143:
3125:
3091:
2882:
2847:
André S, Seed B, Eberle J, Schraut W, Bültmann A, Haas J (February 1998).
2749:
2705:
2656:
2563:
2475:
2319:
2267:
2248:
1607:
In general, co-administration of pro-inflammatory agents (such as various
1538:
Follicular dendritic cells § Antigen capturing, memory B-cell support
38:
6638:
6628:
6489:
6295:
6183:
6151:
6077:
5830:
5822:
4149:"Antigen processing in vivo and the elicitation of primary CTL responses"
2200:
1820:
1445:
1423:
1257:
1249:
1176:
1172:
1134:
1103:
1095:
507:
226:
159:
106:
4813:
Franco A, Guidotti LG, Hobbs MV, Pasquetto V, Chisari FV (August 1997).
4201:
Iwasaki A, Stiernholm BJ, Chan AK, Berinstein NL, Barber BH (May 1997).
2335:"The U.S. government has begun testing its first Zika vaccine in humans"
1895:
1433:) could also internalize DNA. The mechanism of DNA uptake is not known.
6764:
6739:
6429:
6379:
4513:
Casares S, Inaba K, Brumeanu TD, Steinman RM, Bona CA (November 1997).
2595:
2578:
2545:
2192:
2002:"India gives emergency approval for world's first COVID-19 DNA vaccine"
1815:
1800:
1696:
1639:
1582:
1512:
1454:
1427:
1184:
1127:
1039:
1021:
635:
578:
562:
558:
511:
441:
440:(MHC) class I pathway. This is usually accomplished by the addition of
428:-bound antigens are more effective at inducing antibody responses than
396:
357:
353:
171:
4582:
3354:
Daheshia M, Kuklin N, Kanangat S, Manickan E, Rouse BT (August 1997).
1148:
One of the advantages of DNA vaccines is that they are able to induce
6813:
6384:
6257:
5826:
5233:
3669:
3644:
1586:
1448:, or through specific receptors. These might include a 30kDa surface
1196:
1192:
1161:
831:(cationic); microspheres; recombinant adenovirus vectors; attenuated
828:
503:
444:
429:
368:
more commonly used in the target species may improve its expression.
345:
163:
3507:
3024:
1630:
This concept was applied in topical administration of pDNA encoding
1482:
1392:
661:
273:
Potential for atypical processing of bacterial and parasite proteins
6655:
6648:
6643:
6613:
6369:
6305:
6300:
4969:
4665:"Gene vaccination with naked plasmid DNA: mechanism of CTL priming"
1854:"Developing Snake Antivenom Sera by Genetic Immunization: A Review"
1700:
1679:
1472:
1415:
1188:
1168:
1119:
1107:
1035:
997:
832:
603:
590:
584:
569:
534:
526:
479:
455:
294:
195:
112:
5374:
Klinman DM, Yi AK, Beaucage SL, Conover J, Krieg AM (April 1996).
5265:"Contribution of CpG motifs to the immunogenicity of DNA vaccines"
4392:
3979:
Jakob T, Walker PS, Krieg AM, Udey MC, Vogel JC (September 1998).
3946:
490:
Injection in saline is normally conducted intramuscularly (IM) in
6374:
5818:
5735:
2576:
2139:
DNA vaccines for viral infections: basic studies and applications
1851:
1704:
1667:
1500:
1487:
1467:
1402:
When DNA uptake and subsequent expression was first demonstrated
1344:
1068:
616:
gene delivery which include cellular uptake and internalization,
608:
554:
550:
515:
392:
338:
124:
90:
77:
73:
59:
51:
2221:
1699:. Additionally, flanking regions outside this immunostimulatory
6677:
6662:
5953:
4200:
4093:
Fu TM, Friedman A, Ulmer JB, Liu MA, Donnelly JJ (April 1997).
2936:
1741:
1712:
1692:
1596:
single bi- or polycistronic vector, separated by spacer regions
1407:
1261:
1214:
645:
641:
565:
538:
495:
466:
151:
128:
4712:
Chattergoon MA, Robinson TM, Boyer JD, Weiner DB (June 1998).
4711:
3768:
Feltquate DM, Heaney S, Webster RG, Robinson HL (March 1997).
3767:
3583:
3353:
3156:
1440:
uptake of DNA occurs non-specifically, in a method similar to
886:
Inefficient site for uptake due to morphology of muscle tissue
6672:
6557:
6163:
6097:
5538:
5262:
3872:
1624:
836:
349:
5066:
4812:
4613:
4512:
3824:
Boyle CM, Morin M, Webster RG, Robinson HL (December 1996).
3309:
2510:
Sedegah M, Hedstrom R, Hobart P, Hoffman SL (October 1994).
2509:
183:
146:
vaccines by using genetic engineering to transform ordinary
5972:
5481:
5159:
5118:
4861:
4763:
3202:
2457:
2405:
2141:. Advances in Virus Research. Vol. 55. pp. 1–74.
1671:
1659:
1620:
1616:
1507:(APC). After gene gun inoculation to the skin, transfected
1231:
1210:
1206:
1102:(which supports TH2 responses). pDNA injected by needle is
1080:
530:
376:
318:
4466:
2458:
Kilpatrick AM, Dupuis AP, Chang GJ, Kramer LD (May 2010).
1542:
Follicular dendritic cells § Interaction with B-cells
1113:
4764:
Torres CA, Iwasaki A, Barber BH, Robinson HL (May 1997).
4299:
4250:
4146:
3823:
2628:
2289:
2177:
1658:
and potentially toxic, "conventional" adjuvants (such as
1347:
960:
Can increase transfection of intravenously delivered pDNA
939:
Significant shearing of DNA after high-pressure expulsion
932:
DNA can be delivered to cells mm to cm below skin surface
602:
A hybrid vehicle composed of bacteria cell and synthetic
63:
5597:
5373:
5211:
3699:
3203:
Wunderlich G, Moura IC, del Portillo HA (October 2000).
2895:
2726:
2677:
5263:
Klinman DM, Yamshchikov G, Ishigatsubo Y (April 1997).
3505:
537:
microparticles into the target cells, using compressed
478:: by using a standard hypodermic needle, or by using a
5433:
Yi AK, Chace JH, Cowdery JS, Krieg AM (January 1996).
2846:
1707:-rich to ensure binding and uptake into target cells.
4430:
3506:
Sizemore DR, Branstrom AA, Sadoff JC (October 1995).
3055:
1757:
in humans, will be important in pre-clinical trials.
1414:, it was proposed that DNA uptake was facilitated by
1213:
for DNA vaccines against influenza nucleoprotein, or
1118:
Polarisation in T-cell help is useful in influencing
154:
virus by inserting a gene from other viruses (namely
5656:
5311:
3978:
3454:
470:
DNA vaccine and Gene therapy techniques are similar.
5432:
4663:Corr M, Lee DJ, Carson DA, Tighe H (October 1996).
4564:
3405:
2052:
942:
10-fold lower expression, and lower immune response
97:, it is the first DNA vaccine approved for humans.
4662:
4565:Bennett RM, Gabor GT, Merritt MM (December 1985).
4092:
3921:
3056:Rodriguez F, Zhang J, Whitton JL (November 1997).
1270:primary and secondary phases of antibody response.
1217:for DNA vaccines against the murine malaria model
1046:, patterns of lymphocyte trafficking and types of
239:Immune response focused on the antigen of interest
6830:Cedillo v. Secretary of Health and Human Services
5015:
3819:
3817:
3815:
3813:
3198:
3196:
2971:
2790:. Vol. 54. Academic Press. pp. 129–88.
1531:
1483:Antigen presentation by bone marrow-derived cells
1393:Mechanistic basis for DNA-raised immune responses
945:Requires large amounts of DNA (up to 300 μg)
723:Table 2. Summary of plasmid DNA delivery methods
387:(CMV) immediate early promoter, and a retroviral
6916:
4351:
4347:
4345:
4030:
3763:
3761:
3759:
3757:
3755:
3642:
1243:
502:; 2) by temporarily damaging muscle fibres with
236:Polarise T-cell response toward type 1 or type 2
5369:
5367:
4705:
3349:
3347:
3107:
2136:
2132:
2130:
2128:
2126:
2124:
2122:
2120:
2118:
2116:
2114:
2112:
2110:
1685:
957:High levels of immune response can be generated
606:has been employed for DNA vaccine delivery. An
5114:
5112:
4560:
4558:
4508:
4506:
4196:
4194:
4192:
4142:
4140:
4138:
3915:
3810:
3643:Barry MA, Lai WC, Johnston SA (October 1995).
3406:Chen Y, Webster RG, Woodland DL (March 1998).
3193:
2505:
2503:
2357:"DNA Immunization for HIV Vaccine Development"
2108:
2106:
2104:
2102:
2100:
2098:
2096:
2094:
2092:
2090:
2048:
2046:
2044:
2042:
1858:Clinical Toxinology in Asia Pacific and Africa
1351:
1226:
773:Large amounts (approximately 100-200 μg)
111:Conventional vaccines contain either specific
5795:
4920:
4759:
4757:
4342:
3752:
3565:. The State University of New York at Buffalo
3251:
3103:
3101:
3049:
3006:
2889:
2779:
2040:
2038:
2036:
2034:
2032:
2030:
2028:
2026:
2024:
2022:
1760:
1670:toxin, cationic and mannan-coated liposomes,
1570:
1235:Schematic diagram of an antibody and antigens
1156:and immunorecessive CTL epitopes, as well as
1143:
1053:
914:Th2 response may not be the response required
892:Th1 response may not be the response required
651:
5364:
5207:
5205:
4460:
4426:
4424:
4246:
4244:
3974:
3972:
3866:
3560:
3499:
3344:
2777:
2775:
2773:
2771:
2769:
2767:
2765:
2763:
2761:
2759:
1585:or co-stimulatory molecules. These "genetic
1160:, in a manner that appears to mimic natural
1042:and chemokine expression, specific types of
166:). In 1993, Jeffrey Ulmer and co-workers at
5591:
5256:
5153:
5109:
5011:
5009:
5007:
4963:
4855:
4555:
4503:
4189:
4135:
3401:
3399:
2783:
2671:
2500:
2087:
1927:
1925:
1923:
690:. Unsourced material may be challenged and
544:
5802:
5788:
5650:
5532:
4914:
4806:
4754:
4607:
4026:
4024:
3457:Annals of the New York Academy of Sciences
3303:
3245:
3098:
2624:
2622:
2354:
2019:
1016:
5761:
5682:
5633:
5623:
5574:
5564:
5515:
5450:
5409:
5399:
5347:
5337:
5305:
5280:
5202:
5177:
5136:
5092:
5060:
4987:
4938:
4897:
4887:
4830:
4781:
4729:
4688:
4631:
4590:
4538:
4421:
4369:
4352:Justewicz DM, Webster RG (October 1996).
4317:
4293:
4268:
4241:
4172:
4118:
4088:
4086:
4066:
4056:
3996:
3969:
3898:
3849:
3785:
3735:
3725:
3693:
3668:
3636:
3619:
3609:
3423:
3371:
3327:
3228:
3133:
3081:
3032:
2913:
2872:
2840:
2756:
2695:
2646:
2594:
2553:
2535:
2483:
2434:
2382:
2372:
2257:
2247:
1974:
1903:
1877:
1098:(which supports TH1 cell development) or
710:Learn how and when to remove this message
360:than the target species, so altering the
76:containing the DNA sequence encoding the
5004:
4656:
3396:
2720:
2570:
2332:
1920:
1486:
1230:
1081:Basis for different types of T-cell help
1020:
879:pDNA spreads rapidly throughout the body
790:Small amounts (as little as 16 ng)
465:
419:
410:
37:
4021:
2619:
1944:
1942:
1852:Henrique Roman Ramos and Paulo Lee Ho.
1847:
1845:
1397:
1273:robust enough to control HBV infection
1114:Practical uses of polarised T-cell help
868:Intramuscular or Intradermal injection
628:Another approach to DNA vaccination is
371:Another consideration is the choice of
297:that usually consist of a strong viral
14:
6917:
5426:
4083:
3108:Tobery TW, Siliciano RF (March 1997).
3007:Kutzler MA, Weiner DB (October 2008).
2355:Chen Y, Wang S, Lu S (February 2014).
1951:"DNA vaccines: roles against diseases"
1575:
1343:Number of inoculations to obtain high
876:Permanent or semi-permanent expression
644:lung pathogen with a relatively small
356:cells. Pathogens often have different
194:, it is the first DNA vaccine against
5783:
4571:The Journal of Clinical Investigation
3009:"DNA vaccines: ready for prime time?"
2326:
1873:
1871:
1781:
1726:
1030:DNA immunization can raise multiple T
317:may sometimes be included to improve
4669:The Journal of Experimental Medicine
4519:The Journal of Experimental Medicine
3563:"A hybrid vehicle that delivers DNA"
3114:The Journal of Experimental Medicine
1996:
1994:
1948:
1939:
1842:
1799:have been used to build recombinant
1133:for the desired type of response in
889:Relatively large amounts of DNA used
688:adding citations to reliable sources
655:
4921:Doolan DL, Hoffman SL (July 1999).
3252:Weiner DB, Kennedy RC (July 1999).
1522:
917:Requires inert particles as carrier
806:Very high (as much as 300 μg)
623:
485:
24:
6857:Eradication of infectious diseases
6614:Androvax (androstenedione albumin)
5702:
2464:Vector Borne and Zoonotic Diseases
2415:The Journal of Infectious Diseases
2057:. Vol. 42. pp. 343–410.
2055:Advances in Parasitology Volume 42
1884:Emerging Microbes & Infections
1878:Liu S, Wang S, Lu S (April 2016).
1868:
1167:Cytotoxic T-cells recognise small
1011:
820:Small amounts (up to 100 μg)
597:
389:cis-acting transcriptional element
283:
254:Long-term persistence of immunogen
245:Stability for storage and shipping
242:Ease of development and production
25:
6961:
6447:Respiratory syncytial virus (RSV)
3561:Nealon, Cory (25 November 2014).
3278:10.1038/scientificamerican0799-50
1991:
1315:Duration of antigen presentation
904:DNA bombarded directly into cells
801:
784:
6836:Alternative vaccination schedule
5811:Artificial induction of immunity
5709:
5085:10.1128/IAI.68.10.5914-5919.2000
3842:10.1128/JVI.70.12.9074-9078.1996
3221:10.1128/IAI.68.10.5839-5845.2000
3074:10.1128/JVI.71.11.8497-8503.1997
2730:Journal of Immunological Methods
2337:. MIT Technology Review Magazine
2137:Robinson HL, Pertmer TM (2000).
660:
438:major histocompatibility complex
364:of the immunogen to reflect the
288:
264:
5754:10.1128/JVI.78.9.4433-4443.2004
5675:10.1128/IAI.69.9.5565-5572.2001
5475:
4386:
4111:10.1128/JVI.71.4.2715-2721.1997
3891:10.1128/JVI.71.7.5295-5303.1997
3577:
3554:
3448:
3150:
3000:
2965:
2930:
2865:10.1128/JVI.72.2.1497-1503.1998
2451:
2399:
2348:
2283:
2274:
1371:C’-dependent or C’-independent
201:
174:began testing in humans at the
69:DNA vaccines work by injecting
6668:Ovandrotone albumin (Fecundin)
2215:
2171:
1776:cetyltrimethylammonium bromide
1553:
1532:Maintenance of immune response
1329:Kinetics of antibody response
745:Injection (hypodermic needle)
352:usage of pathogenic mRNAs for
142:devised a strategy to produce
13:
1:
6204:Group B streptococcal disease
6023:Vaccines for Children Program
4407:10.1016/j.vaccine.2005.08.013
3171:10.1158/1535-7163.MCT-08-0109
3159:Molecular Cancer Therapeutics
2986:10.1016/j.tibtech.2013.06.001
2951:10.1016/j.tibtech.2009.06.004
2915:10.1016/S0042-6822(03)00459-8
2796:10.1016/S0065-3527(08)60367-X
2147:10.1016/S0065-3527(00)55001-5
2063:10.1016/S0065-308X(08)60152-9
1836:
1786:Recombinant alphavirus-based
1436:Two theories dominate – that
1244:Kinetics of antibody response
1094:can differentiate to secrete
873:No special delivery mechanism
835:vector; aerosolised cationic
553:instillation of naked DNA on
225:Antigen presentation by both
216:
176:National Institutes of Health
140:New York Department of Health
5138:10.4049/jimmunol.164.11.5905
5038:10.1126/science.273.5273.352
4783:10.4049/jimmunol.158.10.4529
4731:10.4049/jimmunol.160.12.5707
4219:10.4049/jimmunol.158.10.4591
3532:10.1126/science.270.5234.299
2784:Lewis PJ, Babiuk LA (1999).
2742:10.1016/0022-1759(96)00035-X
2697:10.4049/jimmunol.159.12.6112
2333:Regalado A (2 August 2016).
1935:. World Health Organization.
1748:has also been demonstrated.
1686:Immunostimulatory CpG motifs
1589:" can be administered as a:
34:messenger RNA (mRNA) vaccine
7:
5282:10.4049/jimmunol.158.8.3635
5179:10.4049/jimmunol.161.4.1875
4832:10.4049/jimmunol.159.4.2001
4633:10.4049/jimmunol.140.9.2937
4319:10.4049/jimmunol.158.8.4008
4270:10.4049/jimmunol.161.5.2325
4165:10.4049/jimmunol.154.9.4414
3998:10.4049/jimmunol.161.6.3042
3787:10.4049/jimmunol.158.5.2278
3425:10.4049/jimmunol.160.5.2425
3373:10.4049/jimmunol.159.4.1945
3329:10.4049/jimmunol.164.9.4635
2648:10.4049/jimmunol.155.4.2039
1809:
1477:cationic liposome packaging
1368:Ab isotype (murine models)
1301:Amount of inducing antigen
1227:Humoral (antibody) response
952:Liposome-mediated delivery
748:Aqueous solution in saline
521:
461:
337:polyadenylation sequences.
168:Merck Research Laboratories
138:and Dennis Panicali at the
42:The making of a DNA vaccine
10:
6966:
5508:10.1038/s41467-018-04234-4
5452:10.4049/jimmunol.156.2.558
4940:10.4049/jimmunol.163.2.884
1761:Enhancing immune responses
1666:, monophosphoryl lipid A,
1571:Immune response modulation
1548:follicular dendritic cells
1535:
1144:Cytotoxic T-cell responses
1054:Other types of T-cell help
795:Pneumatic (jet) injection
652:Helpful tabular comparison
104:
100:
31:
6875:
6844:
6783:
6715:
6606:
6578:
6545:
6219:
6050:
6043:
5962:
5890:
5842:
1649:merozoite surface protein
1284:
1281:
990:
862:
859:
856:
824:
810:
741:
727:
576:microspheres, attenuated
6199:Clostridioides difficile
5339:10.1073/pnas.95.21.12631
4889:10.1073/pnas.93.22.12496
3727:10.1073/pnas.90.24.11478
3013:Nature Reviews. Genetics
1967:10.11599/germs.2013.1034
1772:antigen-presenting cells
1511:migrate to the draining
1505:antigen presenting cells
1158:subdominant CTL epitopes
1088:antigen presenting cells
976:Ineffectiveness in serum
545:Mucosal surface delivery
6950:21st-century inventions
6457:Tick-borne encephalitis
5625:10.1073/pnas.95.13.7648
5566:10.1073/pnas.94.17.9378
4489:10.1126/science.1310359
4434:Journal of Cell Science
4058:10.1073/pnas.93.10.5141
3611:10.1073/pnas.1411355111
3477:10.1196/annals.1322.012
2974:Trends in Biotechnology
2939:Trends in Biotechnology
2537:10.1073/pnas.91.21.9866
2374:10.3390/vaccines2010138
2312:10.1126/science.8456302
1676:carboxymethyl cellulose
1468:polyguanylate sequences
1285:Method of Immunization
1150:cytotoxic T lymphocytes
1048:innate immune responses
1017:Helper T cell responses
770:with variable success)
614:antigen-presenting cell
514:solutions of saline or
6867:List of vaccine topics
5867:Mathematical modelling
5663:Infection and Immunity
5401:10.1073/pnas.93.7.2879
5073:Infection and Immunity
4989:10.1006/viro.1996.0603
4681:10.1084/jem.184.4.1555
4531:10.1084/jem.186.9.1481
4446:10.1242/jcs.103.4.1249
4371:10.1006/viro.1996.0501
3209:Infection and Immunity
2787:DNA vaccines: a review
1949:Khan KH (March 2013).
1765:
1492:
1236:
1027:
781:DNA-coated gold beads
557:surfaces, such as the
549:Alternatives included
471:
222:No risk for infections
180:Inovio Pharmaceuticals
107:Vaccine § History
82:immunological response
71:genetically engineered
43:
27:Vaccine containing DNA
6935:Nucleic acid vaccines
6862:Vaccinate Your Family
6313:Japanese encephalitis
5488:Nature Communications
5439:Journal of Immunology
5269:Journal of Immunology
5166:Journal of Immunology
5125:Journal of Immunology
4927:Journal of Immunology
4819:Journal of Immunology
4770:Journal of Immunology
4718:Journal of Immunology
4620:Journal of Immunology
4306:Journal of Immunology
4257:Journal of Immunology
4207:Journal of Immunology
4153:Journal of Immunology
3985:Journal of Immunology
3774:Journal of Immunology
3412:Journal of Immunology
3360:Journal of Immunology
3316:Journal of Immunology
3126:10.1084/jem.185.5.909
2684:Journal of Immunology
2635:Journal of Immunology
2476:10.1089/vbz.2009.0029
2427:10.1093/infdis/jir054
2249:10.1073/pnas.81.1.193
1656:recombinant cytokines
1613:tumor necrosis factor
1490:
1234:
1181:endoplasmic reticulum
1024:
1004:and large amounts of
929:No particles required
817:Ocular; intravaginal
469:
420:Vaccine insert design
411:Mechanism of plasmids
301:to drive the in vivo
41:
6745:John Franklin Enders
1797:Semliki Forest virus
1627:are sometimes used.
1503:called professional
1457:scavenger receptors.
1398:DNA uptake mechanism
1293:Recombinant protein
825:Cytofectin-mediated
811:Topical application
684:improve this section
184:GeneOne Life Science
156:Herpes simplex virus
121:protein biosynthesis
5931:Virus-like particle
5855:Vaccine ingredients
5742:Journal of Virology
5616:1998PNAS...95.7648S
5557:1997PNAS...94.9378L
5500:2018NatCo...9.1900B
5392:1996PNAS...93.2879K
5330:1998PNAS...9512631K
5324:(21): 12631–12636.
5226:1995Natur.374..546K
5030:1996Sci...273..352S
4880:1996PNAS...9312496M
4874:(22): 12496–12501.
4481:1992Sci...255..410A
4099:Journal of Virology
4049:1996PNAS...93.5141R
3939:1998Natur.392..245B
3879:Journal of Virology
3830:Journal of Virology
3718:1993PNAS...9011478F
3712:(24): 11478–11482.
3661:1995Natur.377..632B
3602:2014PNAS..11112360J
3596:(34): 12360–12365.
3524:1995Sci...270..299S
3469:2004NYASA1028..113L
3270:1999SciAm.281a..50W
3258:Scientific American
3062:Journal of Virology
2853:Journal of Virology
2528:1994PNAS...91.9866S
2304:1993Sci...259.1745U
2298:(5102): 1745–1749.
2240:1984PNAS...81..193P
1896:10.1038/emi.2016.27
1603:, or fusion protein
1576:Cytokine modulation
1412:electron microscopy
1278:
1191:viruses expressing
1124:autoimmune diseases
979:Risk of disease or
857:Method of delivery
853:
724:
572:-DNA preparations,
6902:Never to phase III
6701:Hexavalent vaccine
6515:Epstein–Barr virus
6410:Oxford–AstraZeneca
6103:NmVac4-A/C/Y/W-135
5719:has a profile for
3254:"Genetic vaccines"
2596:10.1038/gt.2014.28
2193:10.1007/bf00470753
1782:Alphavirus vectors
1727:Alternative boosts
1493:
1475:delivery systems,
1296:Natural infection
1276:
1237:
1028:
851:
731:Formulation of DNA
728:Method of delivery
722:
630:expression library
541:as an accelerant.
472:
381:Rous Sarcoma Virus
327:termination signal
248:Cost-effectiveness
44:
6912:
6911:
6824:Vaccines and SIDS
6711:
6710:
6485:Hepatitis A and B
6461:Varicella zoster
5923:Subunit/component
5725:
5610:(13): 7648–7653.
5551:(17): 9378–9383.
5220:(6522): 546–549.
5131:(11): 5905–5912.
5079:(10): 5914–5919.
5024:(5273): 352–354.
4776:(10): 4529–4532.
4724:(12): 5707–5718.
4583:10.1172/JCI112226
4475:(5043): 410–411.
4401:(21): 4482–4489.
4213:(10): 4591–4601.
4043:(10): 5141–5145.
3933:(6673): 245–252.
3836:(12): 9074–9078.
3655:(6550): 632–635.
3518:(5234): 299–302.
3215:(10): 5839–5845.
3068:(11): 8497–8503.
2805:978-0-12-039854-6
2690:(12): 6112–6119.
2522:(21): 9866–9870.
2421:(10): 1396–1404.
1737:Plasmodium yoelii
1664:calcium phosphate
1381:
1380:
1350:and migration of
1074:Plasmodium yoelii
1006:connective tissue
988:
987:
907:Small amounts DNA
849:
848:
814:Aqueous solution
798:Aqueous solution
720:
719:
712:
510:; or 3) by using
329:, such as bovine
325:/transcriptional
311:complementary DNA
192:Cadila Healthcare
95:Cadila Healthcare
16:(Redirected from
6957:
6803:MMR autism fraud
6750:Maurice Hilleman
6735:Hilary Koprowski
6048:
6047:
5804:
5797:
5790:
5781:
5780:
5775:
5765:
5748:(9): 4433–4443.
5723:
5713:
5712:
5697:
5696:
5686:
5669:(9): 5565–5572.
5654:
5648:
5647:
5637:
5627:
5595:
5589:
5588:
5578:
5568:
5536:
5530:
5529:
5519:
5479:
5473:
5472:
5454:
5430:
5424:
5423:
5413:
5403:
5386:(7): 2879–2883.
5371:
5362:
5361:
5351:
5341:
5309:
5303:
5302:
5284:
5275:(8): 3635–3639.
5260:
5254:
5253:
5234:10.1038/374546a0
5209:
5200:
5199:
5181:
5172:(4): 1875–1882.
5157:
5151:
5150:
5140:
5116:
5107:
5106:
5096:
5064:
5058:
5057:
5013:
5002:
5001:
4991:
4967:
4961:
4960:
4942:
4918:
4912:
4911:
4901:
4891:
4859:
4853:
4852:
4834:
4825:(4): 2001–2008.
4810:
4804:
4803:
4785:
4761:
4752:
4751:
4733:
4709:
4703:
4702:
4692:
4675:(4): 1555–1560.
4660:
4654:
4653:
4635:
4626:(9): 2937–2942.
4611:
4605:
4604:
4594:
4577:(6): 2182–2190.
4562:
4553:
4552:
4542:
4525:(9): 1481–1486.
4510:
4501:
4500:
4464:
4458:
4457:
4440:(4): 1249–1259.
4428:
4419:
4418:
4390:
4384:
4383:
4373:
4349:
4340:
4339:
4321:
4312:(8): 4008–4013.
4297:
4291:
4290:
4272:
4263:(5): 2325–2332.
4248:
4239:
4238:
4198:
4187:
4186:
4176:
4159:(9): 4414–4422.
4144:
4133:
4132:
4122:
4105:(4): 2715–2721.
4090:
4081:
4080:
4070:
4060:
4028:
4019:
4018:
4000:
3991:(6): 3042–3049.
3976:
3967:
3966:
3919:
3913:
3912:
3902:
3885:(7): 5295–5303.
3870:
3864:
3863:
3853:
3821:
3808:
3807:
3789:
3780:(5): 2278–2284.
3765:
3750:
3749:
3739:
3729:
3697:
3691:
3690:
3672:
3670:10.1038/377632a0
3640:
3634:
3633:
3623:
3613:
3581:
3575:
3574:
3572:
3570:
3558:
3552:
3551:
3503:
3497:
3496:
3452:
3446:
3445:
3427:
3418:(5): 2425–2432.
3403:
3394:
3393:
3375:
3366:(4): 1945–1952.
3351:
3342:
3341:
3331:
3322:(9): 4635–4640.
3307:
3301:
3300:
3298:
3297:
3288:. Archived from
3249:
3243:
3242:
3232:
3200:
3191:
3190:
3165:(7): 2241–2251.
3154:
3148:
3147:
3137:
3105:
3096:
3095:
3085:
3053:
3047:
3046:
3036:
3004:
2998:
2997:
2969:
2963:
2962:
2934:
2928:
2927:
2917:
2893:
2887:
2886:
2876:
2859:(2): 1497–1503.
2844:
2838:
2837:
2831:
2827:
2825:
2817:
2781:
2754:
2753:
2724:
2718:
2717:
2699:
2675:
2669:
2668:
2650:
2641:(4): 2039–2046.
2626:
2617:
2616:
2598:
2574:
2568:
2567:
2557:
2539:
2507:
2498:
2497:
2487:
2455:
2449:
2448:
2438:
2403:
2397:
2396:
2386:
2376:
2352:
2346:
2345:
2343:
2342:
2330:
2324:
2323:
2287:
2281:
2278:
2272:
2271:
2261:
2251:
2219:
2213:
2212:
2175:
2169:
2168:
2134:
2085:
2084:
2050:
2017:
2016:
2014:
2013:
1998:
1989:
1988:
1978:
1946:
1937:
1936:
1929:
1918:
1917:
1907:
1875:
1866:
1865:
1849:
1599:plasmid-encoded
1523:Target site role
1509:Langerhans cells
1491:A dendritic cell
1471:
1466:the presence of
1458:
1431:Langerhans cells
1353:
1279:
1275:
1271:
1200:signal sequences
982:
981:immune reactions
854:
850:
803:
786:
725:
721:
715:
708:
704:
701:
695:
664:
656:
624:ELI immunization
486:Saline injection
434:cytotoxic T-cell
432:antigens, while
309:of the gene (or
148:smallpox vaccine
117:genetic vaccines
21:
6965:
6964:
6960:
6959:
6958:
6956:
6955:
6954:
6915:
6914:
6913:
6908:
6907:
6892:Clinical trials
6871:
6840:
6779:
6755:Stanley Plotkin
6717:
6707:
6619:Cancer vaccines
6602:
6596:Schistosomiasis
6574:
6568:Trypanosomiasis
6541:
6505:Cytomegalovirus
6415:Pfizer–BioNTech
6215:
6039:
5988:Vaccine wastage
5958:
5886:
5838:
5808:
5778:
5731:
5730:
5729:
5714:
5710:
5705:
5703:Further reading
5700:
5655:
5651:
5596:
5592:
5537:
5533:
5480:
5476:
5431:
5427:
5372:
5365:
5310:
5306:
5261:
5257:
5210:
5203:
5158:
5154:
5117:
5110:
5065:
5061:
5014:
5005:
4968:
4964:
4919:
4915:
4860:
4856:
4811:
4807:
4762:
4755:
4710:
4706:
4661:
4657:
4612:
4608:
4563:
4556:
4511:
4504:
4465:
4461:
4429:
4422:
4391:
4387:
4350:
4343:
4298:
4294:
4249:
4242:
4199:
4190:
4145:
4136:
4091:
4084:
4029:
4022:
3977:
3970:
3920:
3916:
3871:
3867:
3822:
3811:
3766:
3753:
3698:
3694:
3641:
3637:
3582:
3578:
3568:
3566:
3559:
3555:
3504:
3500:
3453:
3449:
3404:
3397:
3352:
3345:
3308:
3304:
3295:
3293:
3250:
3246:
3201:
3194:
3155:
3151:
3106:
3099:
3054:
3050:
3025:10.1038/nrg2432
3019:(10): 776–788.
3005:
3001:
2970:
2966:
2935:
2931:
2894:
2890:
2845:
2841:
2829:
2828:
2819:
2818:
2806:
2782:
2757:
2725:
2721:
2676:
2672:
2627:
2620:
2575:
2571:
2508:
2501:
2456:
2452:
2404:
2400:
2353:
2349:
2340:
2338:
2331:
2327:
2288:
2284:
2279:
2275:
2220:
2216:
2176:
2172:
2157:
2135:
2088:
2073:
2051:
2020:
2011:
2009:
2000:
1999:
1992:
1947:
1940:
1931:
1930:
1921:
1876:
1869:
1850:
1843:
1839:
1812:
1784:
1768:
1763:
1744:malarial model
1729:
1688:
1578:
1573:
1556:
1544:
1534:
1525:
1485:
1465:
1462:ribonucleotides
1453:
1400:
1395:
1377:C’-independent
1354:to bone marrow
1269:
1246:
1229:
1175:) complexed to
1146:
1116:
1092:Dendritic cells
1083:
1056:
1044:immunoglobulins
1033:
1019:
1014:
1012:Immune response
993:
980:
768:intraperitoneal
716:
705:
699:
696:
681:
665:
654:
626:
600:
598:Polymer vehicle
547:
524:
500:electroporation
492:skeletal muscle
488:
464:
426:plasma membrane
422:
413:
385:cytomegalovirus
323:polyadenylation
313:) of interest.
291:
286:
284:Plasmid vectors
267:
219:
204:
144:recombinant DNA
109:
103:
93:. Developed by
36:
28:
23:
22:
18:DNA vaccination
15:
12:
11:
5:
6963:
6953:
6952:
6947:
6942:
6937:
6932:
6927:
6910:
6909:
6906:
6905:
6904:
6903:
6900:
6889:
6883:
6877:
6876:
6873:
6872:
6870:
6869:
6864:
6859:
6854:
6848:
6846:
6842:
6841:
6839:
6838:
6833:
6826:
6821:
6816:
6811:
6806:
6793:
6787:
6785:
6781:
6780:
6778:
6777:
6772:
6770:Katalin Karikó
6767:
6762:
6757:
6752:
6747:
6742:
6737:
6732:
6727:
6721:
6719:
6713:
6712:
6709:
6708:
6706:
6705:
6704:
6703:
6698:
6693:
6688:
6680:
6675:
6670:
6665:
6660:
6659:
6658:
6653:
6652:
6651:
6646:
6636:
6631:
6626:
6616:
6610:
6608:
6604:
6603:
6601:
6600:
6599:
6598:
6593:
6584:
6582:
6576:
6575:
6573:
6572:
6571:
6570:
6562:
6561:
6560:
6549:
6547:
6543:
6542:
6540:
6539:
6538:
6537:
6532:
6527:
6525:Herpes simplex
6522:
6517:
6512:
6507:
6499:
6498:
6497:
6492:
6487:
6479:
6474:
6473:
6472:
6467:
6459:
6454:
6449:
6444:
6443:
6442:
6437:
6432:
6427:
6425:Sinopharm BIBP
6422:
6417:
6412:
6407:
6402:
6397:
6392:
6387:
6382:
6377:
6375:Bharat Biotech
6372:
6362:
6357:
6352:
6347:
6346:
6345:
6340:
6330:
6325:
6320:
6315:
6310:
6309:
6308:
6303:
6293:
6288:
6283:
6278:
6273:
6272:
6271:
6266:
6261:
6246:
6245:
6244:
6234:
6229:
6223:
6221:
6217:
6216:
6214:
6213:
6212:
6211:
6206:
6201:
6193:
6192:
6191:
6186:
6178:
6173:
6172:
6171:
6166:
6156:
6155:
6154:
6144:
6139:
6134:
6133:
6132:
6127:
6117:
6112:
6107:
6106:
6105:
6100:
6090:
6085:
6080:
6075:
6070:
6065:
6060:
6054:
6052:
6045:
6041:
6040:
6038:
6037:
6036:
6035:
6030:
6025:
6020:
6015:
6007:
6006:
6005:
6003:Vaccine injury
6000:
5995:
5990:
5985:
5980:
5975:
5966:
5964:
5963:Administration
5960:
5959:
5957:
5956:
5951:
5946:
5937:
5920:
5919:
5918:
5913:
5905:
5900:
5894:
5892:
5888:
5887:
5885:
5884:
5879:
5874:
5869:
5864:
5863:
5862:
5852:
5846:
5844:
5840:
5839:
5807:
5806:
5799:
5792:
5784:
5777:
5776:
5732:
5715:
5708:
5707:
5706:
5704:
5701:
5699:
5698:
5649:
5590:
5531:
5474:
5445:(2): 558–564.
5425:
5363:
5304:
5255:
5201:
5152:
5108:
5059:
5003:
4982:(2): 293–299.
4962:
4933:(2): 884–892.
4913:
4854:
4805:
4753:
4704:
4655:
4606:
4554:
4502:
4459:
4420:
4385:
4341:
4292:
4240:
4188:
4134:
4082:
4020:
3968:
3914:
3865:
3809:
3751:
3692:
3635:
3576:
3553:
3498:
3463:(1): 113–121.
3447:
3395:
3343:
3302:
3244:
3192:
3149:
3120:(5): 909–920.
3097:
3048:
2999:
2980:(9): 539–547.
2964:
2945:(9): 503–511.
2929:
2908:(1): 134–146.
2888:
2839:
2830:|journal=
2804:
2755:
2719:
2670:
2618:
2589:(5): 514–521.
2569:
2499:
2470:(4): 377–380.
2450:
2398:
2367:(1): 138–159.
2347:
2325:
2282:
2273:
2234:(1): 193–197.
2214:
2187:(3): 173–177.
2181:Mycopathologia
2170:
2155:
2086:
2071:
2018:
1990:
1938:
1933:"DNA vaccines"
1919:
1867:
1840:
1838:
1835:
1834:
1833:
1828:
1823:
1818:
1811:
1808:
1783:
1780:
1767:
1764:
1762:
1759:
1750:Rhesus monkeys
1728:
1725:
1687:
1684:
1605:
1604:
1597:
1594:
1577:
1574:
1572:
1569:
1555:
1552:
1533:
1530:
1524:
1521:
1495:Studies using
1484:
1481:
1399:
1396:
1394:
1391:
1379:
1378:
1375:
1372:
1369:
1365:
1364:
1361:
1358:
1355:
1340:
1339:
1336:
1333:
1330:
1326:
1325:
1324:several weeks
1322:
1319:
1318:several weeks
1316:
1312:
1311:
1308:
1305:
1302:
1298:
1297:
1294:
1291:
1287:
1286:
1283:
1254:haemagglutinin
1245:
1242:
1228:
1225:
1154:immunodominant
1145:
1142:
1122:responses and
1115:
1112:
1082:
1079:
1055:
1052:
1031:
1018:
1015:
1013:
1010:
992:
989:
986:
985:
984:
983:
977:
974:
969:
968:
967:
964:
961:
958:
953:
949:
948:
947:
946:
943:
940:
935:
934:
933:
930:
925:
924:Jet injection
921:
920:
919:
918:
915:
910:
909:
908:
905:
900:
896:
895:
894:
893:
890:
887:
882:
881:
880:
877:
874:
869:
865:
864:
861:
858:
847:
846:
843:
840:
826:
822:
821:
818:
815:
812:
808:
807:
804:
799:
796:
792:
791:
788:
782:
779:
775:
774:
771:
749:
746:
743:
739:
738:
737:Amount of DNA
735:
732:
729:
718:
717:
668:
666:
659:
653:
650:
625:
622:
599:
596:
546:
543:
523:
520:
487:
484:
463:
460:
421:
418:
412:
409:
331:growth hormone
290:
287:
285:
282:
281:
280:
277:
274:
271:
266:
263:
262:
261:
255:
252:
249:
246:
243:
240:
237:
234:
223:
218:
215:
203:
200:
102:
99:
26:
9:
6:
4:
3:
2:
6962:
6951:
6948:
6946:
6943:
6941:
6940:Gene delivery
6938:
6936:
6933:
6931:
6928:
6926:
6923:
6922:
6920:
6901:
6899:
6896:
6895:
6893:
6890:
6887:
6884:
6882:
6879:
6878:
6874:
6868:
6865:
6863:
6860:
6858:
6855:
6853:
6850:
6849:
6847:
6843:
6837:
6834:
6832:
6831:
6827:
6825:
6822:
6820:
6817:
6815:
6812:
6810:
6807:
6804:
6802:
6797:
6794:
6792:
6789:
6788:
6786:
6782:
6776:
6775:Drew Weissman
6773:
6771:
6768:
6766:
6763:
6761:
6760:H. Fred Clark
6758:
6756:
6753:
6751:
6748:
6746:
6743:
6741:
6738:
6736:
6733:
6731:
6730:Louis Pasteur
6728:
6726:
6725:Edward Jenner
6723:
6722:
6720:
6714:
6702:
6699:
6697:
6696:DTwP-HepB-Hib
6694:
6692:
6691:DTaP-IPV-HepB
6689:
6687:
6684:
6683:
6682:combination:
6681:
6679:
6676:
6674:
6671:
6669:
6666:
6664:
6661:
6657:
6654:
6650:
6647:
6645:
6642:
6641:
6640:
6637:
6635:
6632:
6630:
6627:
6625:
6622:
6621:
6620:
6617:
6615:
6612:
6611:
6609:
6605:
6597:
6594:
6592:
6589:
6588:
6586:
6585:
6583:
6581:
6580:Helminthiasis
6577:
6569:
6566:
6565:
6563:
6559:
6556:
6555:
6554:
6551:
6550:
6548:
6544:
6536:
6533:
6531:
6528:
6526:
6523:
6521:
6518:
6516:
6513:
6511:
6508:
6506:
6503:
6502:
6500:
6496:
6493:
6491:
6488:
6486:
6483:
6482:
6481:combination:
6480:
6478:
6475:
6471:
6468:
6466:
6463:
6462:
6460:
6458:
6455:
6453:
6450:
6448:
6445:
6441:
6438:
6436:
6433:
6431:
6428:
6426:
6423:
6421:
6418:
6416:
6413:
6411:
6408:
6406:
6403:
6401:
6398:
6396:
6393:
6391:
6388:
6386:
6383:
6381:
6378:
6376:
6373:
6371:
6368:
6367:
6366:
6363:
6361:
6358:
6356:
6353:
6351:
6348:
6344:
6341:
6339:
6336:
6335:
6334:
6331:
6329:
6326:
6324:
6321:
6319:
6316:
6314:
6311:
6307:
6304:
6302:
6299:
6298:
6297:
6294:
6292:
6289:
6287:
6284:
6282:
6279:
6277:
6274:
6270:
6267:
6265:
6262:
6259:
6255:
6252:
6251:
6250:
6247:
6243:
6240:
6239:
6238:
6235:
6233:
6230:
6228:
6225:
6224:
6222:
6218:
6210:
6207:
6205:
6202:
6200:
6197:
6196:
6194:
6190:
6187:
6185:
6184:DPT/DTwP/DTaP
6182:
6181:
6180:combination:
6179:
6177:
6174:
6170:
6167:
6165:
6162:
6161:
6160:
6157:
6153:
6150:
6149:
6148:
6145:
6143:
6140:
6138:
6135:
6131:
6128:
6126:
6123:
6122:
6121:
6118:
6116:
6113:
6111:
6108:
6104:
6101:
6099:
6096:
6095:
6094:
6093:Meningococcus
6091:
6089:
6086:
6084:
6083:Leptospirosis
6081:
6079:
6076:
6074:
6071:
6069:
6066:
6064:
6061:
6059:
6056:
6055:
6053:
6049:
6046:
6042:
6034:
6031:
6029:
6026:
6024:
6021:
6019:
6018:Vaccine court
6016:
6014:
6011:
6010:
6008:
6004:
6001:
5999:
5996:
5994:
5991:
5989:
5986:
5984:
5981:
5979:
5976:
5974:
5973:GAVI Alliance
5971:
5970:
5968:
5967:
5965:
5961:
5955:
5952:
5950:
5947:
5945:
5941:
5938:
5936:
5932:
5928:
5924:
5921:
5917:
5914:
5912:
5909:
5908:
5906:
5904:
5901:
5899:
5896:
5895:
5893:
5889:
5883:
5880:
5878:
5875:
5873:
5870:
5868:
5865:
5861:
5858:
5857:
5856:
5853:
5851:
5848:
5847:
5845:
5841:
5836:
5832:
5828:
5824:
5820:
5816:
5812:
5805:
5800:
5798:
5793:
5791:
5786:
5785:
5782:
5773:
5769:
5764:
5759:
5755:
5751:
5747:
5743:
5739:
5734:
5733:
5727:
5726:
5718:
5694:
5690:
5685:
5680:
5676:
5672:
5668:
5664:
5660:
5653:
5645:
5641:
5636:
5631:
5626:
5621:
5617:
5613:
5609:
5605:
5601:
5594:
5586:
5582:
5577:
5572:
5567:
5562:
5558:
5554:
5550:
5546:
5542:
5535:
5527:
5523:
5518:
5513:
5509:
5505:
5501:
5497:
5493:
5489:
5485:
5478:
5470:
5466:
5462:
5458:
5453:
5448:
5444:
5440:
5436:
5429:
5421:
5417:
5412:
5407:
5402:
5397:
5393:
5389:
5385:
5381:
5377:
5370:
5368:
5359:
5355:
5350:
5345:
5340:
5335:
5331:
5327:
5323:
5319:
5315:
5308:
5300:
5296:
5292:
5288:
5283:
5278:
5274:
5270:
5266:
5259:
5251:
5247:
5243:
5239:
5235:
5231:
5227:
5223:
5219:
5215:
5208:
5206:
5197:
5193:
5189:
5185:
5180:
5175:
5171:
5167:
5163:
5156:
5148:
5144:
5139:
5134:
5130:
5126:
5122:
5115:
5113:
5104:
5100:
5095:
5090:
5086:
5082:
5078:
5074:
5070:
5063:
5055:
5051:
5047:
5043:
5039:
5035:
5031:
5027:
5023:
5019:
5012:
5010:
5008:
4999:
4995:
4990:
4985:
4981:
4977:
4973:
4966:
4958:
4954:
4950:
4946:
4941:
4936:
4932:
4928:
4924:
4917:
4909:
4905:
4900:
4895:
4890:
4885:
4881:
4877:
4873:
4869:
4865:
4858:
4850:
4846:
4842:
4838:
4833:
4828:
4824:
4820:
4816:
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3292:on 2009-03-25
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2407:Ledgerwood JE
2402:
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2370:
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2362:
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2351:
2336:
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2166:
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2158:
2156:9780120398553
2152:
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2119:
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2103:
2101:
2099:
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2072:9780120317424
2068:
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2041:
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2037:
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2025:
2023:
2007:
2003:
1997:
1995:
1986:
1982:
1977:
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1968:
1964:
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1956:
1952:
1945:
1943:
1934:
1928:
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1824:
1822:
1819:
1817:
1814:
1813:
1807:
1805:
1802:
1798:
1794:
1793:Sindbis virus
1789:
1779:
1777:
1773:
1758:
1756:
1755:P. falciparum
1751:
1747:
1743:
1738:
1733:
1724:
1720:
1716:
1714:
1708:
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1702:
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1469:
1463:
1456:
1451:
1447:
1443:
1439:
1434:
1432:
1429:
1425:
1421:
1420:keratinocytes
1417:
1413:
1409:
1405:
1390:
1387:
1376:
1374:C’-dependent
1373:
1370:
1367:
1366:
1362:
1359:
1356:
1349:
1346:
1342:
1341:
1337:
1334:
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1009:
1007:
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978:
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944:
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898:
897:
891:
888:
885:
884:
883:
878:
875:
872:
871:
870:
867:
866:
863:Disadvantage
855:
844:
841:
839:formulations
838:
834:
830:
827:
823:
819:
816:
813:
809:
805:
800:
797:
794:
793:
789:
783:
780:
777:
776:
772:
769:
765:
761:
757:
753:
750:
747:
744:
740:
736:
734:Target tissue
733:
730:
726:
714:
711:
703:
693:
689:
685:
679:
678:
674:
669:This section
667:
663:
658:
657:
649:
647:
643:
639:
637:
631:
621:
619:
615:
611:
610:
605:
595:
593:
592:
587:
586:
581:
580:
575:
574:biodegradable
571:
567:
564:
560:
556:
552:
542:
540:
536:
532:
528:
519:
517:
513:
509:
505:
501:
497:
496:intradermally
493:
483:
481:
477:
468:
459:
457:
453:
448:
446:
443:
439:
435:
431:
427:
417:
408:
404:
402:
398:
394:
390:
386:
382:
378:
374:
369:
367:
363:
362:gene sequence
359:
355:
351:
347:
342:
340:
339:Polycistronic
336:
335:beta-globulin
332:
328:
324:
320:
316:
312:
308:
304:
303:transcription
300:
296:
289:Vector design
278:
275:
272:
269:
268:
265:Disadvantages
259:
256:
253:
250:
247:
244:
241:
238:
235:
232:
228:
224:
221:
220:
214:
211:
208:
199:
197:
193:
188:
185:
181:
177:
173:
169:
165:
161:
157:
153:
149:
145:
141:
137:
136:Enzo Paoletti
132:
130:
126:
122:
118:
114:
108:
98:
96:
92:
87:
83:
79:
75:
72:
67:
65:
61:
57:
53:
50:is a type of
49:
40:
35:
30:
19:
6925:DNA vaccines
6852:Epidemiology
6828:
6800:
6686:DTaP-IPV/Hib
6477:Yellow fever
6390:EpiVacCorona
6147:Tuberculosis
6120:Pneumococcal
6088:Lyme disease
5939:
5916:Heterologous
5815:Immunization
5745:
5741:
5722:DNA vaccine
5721:
5666:
5662:
5652:
5607:
5603:
5593:
5548:
5544:
5534:
5491:
5487:
5477:
5442:
5438:
5428:
5383:
5379:
5321:
5317:
5307:
5272:
5268:
5258:
5217:
5213:
5169:
5165:
5155:
5128:
5124:
5076:
5072:
5062:
5021:
5017:
4979:
4975:
4965:
4930:
4926:
4916:
4871:
4867:
4857:
4822:
4818:
4808:
4773:
4769:
4721:
4717:
4707:
4672:
4668:
4658:
4623:
4619:
4609:
4574:
4570:
4522:
4518:
4472:
4468:
4462:
4437:
4433:
4398:
4394:
4388:
4364:(1): 10–17.
4361:
4357:
4309:
4305:
4295:
4260:
4256:
4210:
4206:
4156:
4152:
4102:
4098:
4040:
4036:
3988:
3984:
3930:
3926:
3923:Banchereau J
3917:
3882:
3878:
3868:
3833:
3829:
3777:
3773:
3709:
3705:
3695:
3652:
3648:
3638:
3593:
3589:
3579:
3567:. Retrieved
3556:
3515:
3511:
3501:
3460:
3456:
3450:
3415:
3411:
3363:
3359:
3319:
3315:
3305:
3294:. Retrieved
3290:the original
3264:(1): 50–57.
3261:
3257:
3247:
3212:
3208:
3162:
3158:
3152:
3117:
3113:
3065:
3061:
3051:
3016:
3012:
3002:
2977:
2973:
2967:
2942:
2938:
2932:
2905:
2901:
2891:
2856:
2852:
2842:
2786:
2736:(1): 29–40.
2733:
2729:
2722:
2687:
2683:
2673:
2638:
2634:
2586:
2583:Gene Therapy
2582:
2572:
2519:
2515:
2467:
2463:
2453:
2418:
2414:
2401:
2364:
2360:
2350:
2339:. Retrieved
2328:
2295:
2291:
2285:
2276:
2231:
2227:
2217:
2184:
2180:
2173:
2138:
2054:
2010:. Retrieved
2008:. 2021-08-20
2005:
1961:(1): 26–35.
1958:
1954:
1887:
1883:
1861:
1857:
1831:mRNA vaccine
1826:Gene therapy
1785:
1769:
1754:
1745:
1736:
1734:
1730:
1721:
1717:
1709:
1689:
1653:
1643:
1635:
1629:
1609:interleukins
1606:
1579:
1557:
1545:
1526:
1517:
1494:
1437:
1435:
1403:
1401:
1382:
1321:< 1 week
1290:DNA vaccine
1266:
1247:
1238:
1218:
1204:
1166:
1147:
1117:
1084:
1072:
1064:
1061:
1057:
1029:
1002:basal lamina
994:
764:subcutaneous
754:(skeletal);
706:
700:October 2021
697:
682:Please help
670:
634:
627:
607:
601:
589:
583:
577:
548:
525:
489:
473:
452:conformation
449:
423:
414:
405:
370:
343:
292:
257:
212:
209:
205:
202:Applications
189:
133:
110:
68:
47:
45:
29:
6888:from market
6784:Controversy
6718:researchers
6634:Hepatitis B
6520:Hepatitis C
6465:Chicken pox
6291:Hepatitis E
6286:Hepatitis B
6281:Hepatitis A
6232:Chikungunya
6209:Shigellosis
6063:Brucellosis
5949:Therapeutic
5903:Inactivated
5843:Development
5831:Inoculation
5823:Vaccination
5494:(1): 1900.
3569:16 December
1821:HIV vaccine
1746:P. knowlesi
1697:pyrimidines
1695:and two 3’
1645:P. chabaudi
1583:lymphokines
1554:Interferons
1446:pinocytosis
1424:fibroblasts
1338:rapid rise
1335:rapid rise
1258:bone marrow
1250:hepatitis B
1177:MHC class I
1173:amino acids
1135:preclinical
1104:endocytosed
742:Parenteral
508:bupivacaine
358:AT-contents
307:translation
227:MHC class I
160:hepatitis B
58:a specific
48:DNA vaccine
6919:Categories
6819:Thiomersal
6765:Paul Offit
6740:Jonas Salk
6716:Inventors/
6587:research:
6564:research:
6501:research:
6430:Skycovione
6420:Sanofi–GSK
6365:SARS-CoV-2
6276:Hantavirus
6242:rVSV-ZEBOV
6227:Adenovirus
6195:research:
6073:Diphtheria
5911:Attenuated
3296:2007-11-21
2341:2016-08-06
2012:2021-08-22
1890:(4): e33.
1864:: 401–414.
1837:References
1816:Vector DNA
1801:alphavirus
1536:See also:
1513:lymph node
1455:macrophage
1428:epithelial
1332:slow rise
1310:? (ng-μg)
1185:N-terminus
1128:predisease
1040:lymphokine
860:Advantage
636:Mycoplasma
618:phagosomal
579:Salmonalla
512:hypertonic
442:N-terminal
397:adenovirus
354:eukaryotic
333:or rabbit
217:Advantages
172:Zika virus
105:See also:
86:veterinary
56:transfects
32:See also:
6898:Phase III
6886:Withdrawn
6814:Pox party
6624:ALVAC-CEA
6546:Protozoan
6435:Sputnik V
6385:CoronaVac
6355:Rotavirus
6258:Pandemrix
6110:Pertussis
6051:Bacterial
5935:Synthetic
5898:Conjugate
5850:Adjuvants
5827:Infection
5724:(Q578537)
2832:ignored (
2822:cite book
1804:replicons
1636:P. yoelii
1587:adjuvants
1220:P. yoelii
1197:ubiquitin
1193:influenza
1162:infection
1071:parasite
899:Gene gun
845:variable
829:Liposomes
778:Gene gun
671:does not
504:myotoxins
447:signals.
445:ubiquitin
430:cytosolic
233:molecules
164:influenza
134:In 1983,
6945:Virology
6656:Prostvac
6649:Gardasil
6644:Cervarix
6591:Hookworm
6470:Shingles
6452:Smallpox
6370:Corbevax
6306:Gardasil
6301:Cervarix
6044:Vaccines
5998:Schedule
5969:Global:
5877:Timeline
5819:Vaccines
5772:15078924
5693:11500430
5526:29765016
5469:42145608
5299:41861994
5196:36488254
5147:10820272
5103:10992502
4976:Virology
4957:41651105
4949:10395683
4849:20528634
4800:45069087
4748:33499198
4650:22923379
4415:16310901
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