Malaria vaccine - Knowledge

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targeting antigens, thus potentially eliciting an immune response. Theoretically, each developmental stage could have a vaccine developed specifically to target the parasite. Moreover, any vaccine produced would ideally have the ability to be of therapeutic value as well as preventing further transmission and is likely to consist of a combination of antigens from different phases of the parasite's development. More than 30 of these antigens are being researched by teams all over the world in the hope of identifying a combination that can elicit immunity in the inoculated individual. Some of the approaches involve surface expression of the antigen, inhibitory effects of specific antibodies on the lifecycle and the protective effects through immunization or passive transfer of antibodies between an immune and a non-immune host. The majority of research into malarial vaccines has focused on the

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protection against symptomatic malaria for at least 2 years. A phase III trial with 4,800 children across four African countries was reported in November 2022, demonstrating vaccine efficacy of 74% against a severe malaria episode. Further data from multiple studies is being collected. As of April 2023 data from the phase III study had not been formally published, but late-stage data from the study was shared with regulatory authorities.

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seems to wane with time. After four years, reductions were 36 percent for children who received three shots and a booster dose. Missing the booster dose reduced the efficacy against severe malaria to a negligible effect. The vaccine was shown to be less effective for infants. Three doses of vaccine plus a booster reduced the risk of clinical episodes by 26 percent over three years but offered no significant protection against severe malaria.

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no previous exposure. This is another major public health problem, with malaria presenting as one of the most substantial threats to travelers' health. Problems with the available pharmaceutical therapies include costs, availability, adverse effects and contraindications, inconvenience, and compliance, many of which would be reduced or eliminated if an effective (greater than 85–90%) vaccine was developed.

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low antibody response in people naturally exposed to the parasite. The high susceptibility of PfRH5 to the cross-strain neutralizing vaccine-induced antibody demonstrated a significant promise for preventing malaria in the long and often difficult road of vaccine development. According to Professor Adrian Hill, a Wellcome Trust Senior Investigator at the

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development of resistance. The process of evolutionary change is one of the key considerations necessary when considering potential vaccine candidates. The development of resistance could cause a significant reduction in efficacy of any potential vaccine thus rendering useless a carefully developed and effective treatment.

823:"Anti-toxic immunity" addresses the symptoms; it refers to the suppression of the immune response associated with the production of factors that either induce symptoms or reduce the effect that any toxic by-products (of micro-organism presence) have on the development of disease. For example, it has been shown that 602:, and was tested extensively in endemic areas in the 1990s. Clinical trials showed it to be insufficiently effective, with 28% efficacy in South America and minimal or no efficacy in Africa. This vaccine had no protective effect in the largest placebo controlled randomized trial in South East Asia and was abandoned. 1083:. The researchers found that the binding is a two-step process that involves two copies of the parasite protein acting together like a pair of tongs that "clamp" two copies of DARC. Antibodies that interfere with the binding by either targeting the key region of the DARC or the DBP will prevent the infection. 1099:

parasite. Tanzanian and Kenyan children who have antibodies to PfSEA-1 were found to have fewer parasites in their bloodstream and a milder case of malaria. By blocking the schizont outlet, the PfSEA-1 vaccine may work synergistically with vaccines targeting the other stages of the malaria lifecycle such as

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relies on a red blood cell surface receptor, known as 'basigin', to invade the cells by binding a protein PfRH5 to the receptor. Unlike other antigens of the malaria parasite which are often genetically diverse, the PfRH5 antigen appears to have little genetic diversity. It was found to induce very

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By their very nature, protozoa are more complex organisms than bacteria and viruses, with more complicated structures and lifecycles. This presents problems in vaccine development but also increases the number of potential targets for a vaccine. These have been summarised into the lifecycle stage and

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through adhesion to an external surface of the antigenic substances, thus 'marking' it as offensive. Humoral or cell-mediated immunity consists of many interlinking mechanisms that essentially aim to prevent infection entering the body (through external barriers or hostile internal environments) and

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A chemical compound undergoing trials for the treatment of tuberculosis and cancer—the JmJc inhibitor ML324 and the antitubercular clinical candidate SQ109—is potentially a new line of drugs to treat malaria and kill the parasite in its infectious stage. More tests still need to be carried out before

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million children in Ghana, Kenya and Malawi had received at least one injection of the vaccine, with more than 4.5 million doses of the vaccine administered through the countries' routine immunization programs. The next 9 countries to receive the vaccine over the next 2 years are Benin, Burkina Faso,

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In October 2013, preliminary results of a phase III clinical trial indicated that RTS,S/AS01 reduced the number of cases among young children by almost 50 percent and among infants by around 25 percent. The study ended in 2014. The effects of a booster dose were positive, even though overall efficacy

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from producing multiple sporozoites in the gut wall of the mosquito. It therefore would be used as part of a policy directed at eliminating the parasite from areas of low prevalence or to prevent the development and spread of vaccine-resistant parasites. This type of transmission-blocking vaccine is

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expression on the surface of erythrocytes. Instead, malarial antigens are expressed, and it is this towards which the antibodies could potentially be directed. Another approach would be to attempt to block the process of erythrocyte adherence to blood vessel walls. It is thought that this process is

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Individuals who are exposed to the parasite in endemic countries develop acquired immunity against disease and death. Such immunity does not, however prevent malarial infection; immune individuals often harbour asymptomatic parasites in their blood. This does, however, imply that it is possible to

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malaria in sub-Saharan Africa, with the primary objective to reduce the number of severe malaria cases and deaths in infants and children exposed to high transmission rates. The Type 2 vaccine could be thought of as a 'travelers' vaccine,' aiming to prevent all clinical symptoms in individuals with

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PfSEA-1, a 244 kd malaria antigen expressed in the schizont-infected RBCs. Mice vaccinated with the recombinant PfSEA-1 produced antibodies which interrupted the schizont rupture from the RBCs and decreased the parasite replication. The vaccine protected the mice from the lethal challenge of the

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The lifecycle of the malaria parasite is particularly complex, presenting initial developmental problems. Despite the huge number of vaccines available, there are none that target parasitic infections. The distinct developmental stages involved in the lifecycle present numerous opportunities for

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A completely effective vaccine is not available for malaria, although several vaccines are under development. Multiple vaccine candidates targeting the blood-stage of the parasite's lifecycle have been insufficient on their own. Several potential vaccines targeting the pre-erythrocytic stage are

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The initial stage in the lifecycle, following inoculation, is a relatively short "pre-erythrocytic" or "hepatic" phase. A vaccine at this stage must have the ability to protect against sporozoites invading and possibly inhibiting the development of parasites in the hepatocytes (through inducing

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malaria. Thus a therapeutic vaccine could target the production of TNF-a, preventing respiratory distress and cerebral symptoms. This approach has serious limitations as it would not reduce the parasitic load; rather, it only reduces the associated pathology. As a result, there are substantial

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A phase II trial was reported in April 2021, with a vaccine efficacy of 77% and antibody levels significantly higher than with the RTS,S vaccine. A booster shot of R21/Matrix-M that is given 12 months after the primary three-dose regimen maintains a high efficacy against malaria, providing high

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In 1995 a field trial involving 19-5.1 proved to be very successful. Out of 194 children vaccinated, none developed symptomatic malaria in the 12-week follow-up period, and only 8 failed to have higher levels of antibody present. The vaccine consists of the schizont export protein (5.1) and 19

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Taking this information into consideration an ideal vaccine candidate would attempt to generate a more substantial cell-mediated and antibody response on parasite presentation. This would have the benefit of increasing the rate of parasite clearance, thus reducing the experienced symptoms and

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has a very high rate of replication, much higher than that actually needed to ensure transmission in the parasite's lifecycle. This enables pharmaceutical treatments that are effective at reducing the reproduction rate, but not halting it, to exert a high selection pressure, thus favoring the

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to elicit an immune response. Clinical trials have been promising, with trials in Africa, Europe, and the US protecting over 80% of volunteers. It has been subject to some criticism regarding the ultimate feasibility of large-scale production and delivery in Africa, since it must be stored in

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in addition to generating an elevated cell-mediated response. Potential antigens against which a vaccine could be targeted will be discussed in greater depth later. Antibodies are part of the specific immune response. They exert their effect by activating the complement cascade, stimulating

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RTS,S/AS01 (brand name Mosquirix) is the first malaria vaccine approved for public use. It requires at least three doses in infants by age 2, with a fourth dose extending the protection for another 1–2 years. The vaccine reduces hospital admissions from severe malaria by around 30%.

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and their cooperators showed that antibodies against PfEMP1 provide protective immunity, while antibodies developed against other surface antigens do not. Their results demonstrated that PfEMP1 could be a target to develop an effective vaccine which will reduce risk of developing

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to boost the immune response. Infection is prevented by inducing high antibody titers that block the parasite from infecting the liver. In November 2012, a Phase III trial of RTS,S found that it provided modest protection against both clinical and severe malaria in young infants.

635:) were derived from the sporozoite phase. The liver stage antigen 1 (LSA1), three from the erythrocytic stage (merozoite surface protein 1, serine repeat antigen, and AMA-1), and one sexual stage antigen (the 25-kDa Pfs25) were included. This was first investigated using 423:

The most effective malaria vaccine is R21/Matrix-M, with 77% efficacy shown in initial trials. It is the first vaccine that meets the World Health Organization's goal of a malaria vaccine with at least 75% efficacy. It was developed through a collaboration involving the

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million children living in areas with moderate-to-high malaria transmission. It requires at least three doses in infants by age 2, and a fourth dose extends the protection for another 1–2 years. The vaccine reduces hospital admissions from severe malaria by around 30%.

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approved the use of the R21 vaccine in April 2023, for use in children aged between five months to three years old. The Serum Institute of India is preparing to produce between 100–200 million doses of the vaccine per year, and is constructing a vaccine factory in

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The epidemiology of malaria varies enormously across the globe and has led to the belief that it may be necessary to adopt very different vaccine development strategies to target the different populations. A Type 1 vaccine is suggested for those exposed mostly to

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and PFs25). Later trials in humans, despite demonstrating cellular immune responses in over 90% of the subjects, had very poor antibody responses. Despite this following administration of the vaccine, some candidates had complete protection when challenged with

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Research continues with other malaria vaccines. The most effective malaria vaccine is the R21/Matrix-M, with a 77% efficacy rate shown in initial trials and significantly higher antibody levels than with the RTS,S vaccine. It is the first vaccine that meets the

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Aponte JJ, Aide P, Renom M, Mandomando I, Bassat Q, Sacarlal J, et al. (November 2007). "Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I/IIb trial".

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can be achieved by attempting to target multiple phases in the lifecycle. This is additionally beneficial in reducing the possibility of resistant parasites developing. The use of multiple-parasite antigens can therefore have a synergistic or additive effect.

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The last phase of the lifecycle that has the potential to be targeted by a vaccine is the "sexual stage". This would not give any protective benefits to the individual inoculated but would prevent further transmission of the parasite by preventing the

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Nosten F, Luxemburger C, Kyle DE, Ballou WR, Wittes J, Wah E, et al. (September 1996). "Randomised double-blind placebo-controlled trial of SPf66 malaria vaccine in children in northwestern Thailand. Shoklo SPf66 Malaria Vaccine Trial Group".

820:) that target foreign bodies by a variety of different mechanisms. In the case of malaria, both systems would be targeted to attempt to increase the potential response generated, thus ensuring the maximum chance of preventing disease. 991:

potentially very important. The evolution of resistance in the malaria parasite occurs very quickly, potentially making any vaccine redundant within a few generations. This approach to the prevention of spread is therefore essential.

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accountable for much of the clinical syndrome associated with malarial infection; therefore, a vaccine given during this stage would be therapeutic and hence administered during clinical episodes to prevent further deterioration.

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binds the Duffy antigen (DARC) on the surface of RBC, process for the parasite to enter the RBC is initiated. Structures of the core region of DARC and the receptor binding pocket of DBP have been mapped by scientists at the

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Heppner DG, Cummings JF, Ockenhouse CF, Kester KE, Cohen J, Ballou WR (2004). "Adjuvanted RTS, S and other protein-based pre-erythrocytic stage malaria vaccines.". In Levine MM, Kaper JB, Rappuoli R, Liu MA, Good MR (eds.).

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reticulocyte-binding protein homologue 5 (PfRH5) was found to induce an antibody response in an animal model. The results of this new vaccine confirmed the utility of a key discovery reported from scientists at the

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The CSP (Circum-Sporozoite Protein) was a vaccine developed that initially appeared promising enough to undergo trials. It is also based on the circumsporozoite protein, but additionally has the recombinant

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Egress Antigen-1 (PfSEA-1) were found to disable the parasite's ability to rupture from the infected red blood cells (RBCs), thus preventing it from continuing with its lifecycle. Researchers from

1043:, the next step would be the safety tests of this vaccine. At the time (2011) it was projected that if these proved successful, the clinical trials in patients could begin within two to three years. 998:, which are present during the entire lifecycle of the malaria parasite. Research is underway on this, yet production of an actual vaccine targeting these protein kinases may still take a long time. 1922: 2288: 3062: 333:(EMA) on the proposal for the vaccine to be used to vaccinate children aged 6 weeks to 17 months outside the European Union. A pilot project for vaccination was launched on 23 April 2019 in 3647:

Stanisic DI, Martin LB, Good MF, Anders RF. "Plasmodium falciparum Asexual Blood Stage Vaccine Candidates: Current Status.". In Levine MM, Kaper JB, Rappuoli R, Liu MA, Good MR (eds.).

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The task of developing a preventive vaccine for malaria is a complex process. There are a number of considerations to be made concerning what strategy a potential vaccine should adopt.

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symmetry and carried on its surface up to 60 copies of the RTS,S protein. The researchers claimed that the density of the protein was much higher than the 14% of the GSK vaccine.

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Hoffman SL, Doolan DL, Richie TL (January 2004). "Malaria: a complex disease that may require a complex vaccine.". In Levine MM, Kaper JB, Rappuoli R, Liu MA, Good MR (eds.).

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which affected an estimated 249 million people globally in 85 malaria endemic countries and areas and caused 608,000 deaths in 2022. The first approved vaccine for malaria is

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million doses of the RTS,S vaccine over three years. More than 30 countries have areas with moderate to high malaria transmission where the vaccine is expected to be useful.

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In October 2021, the vaccine was endorsed by the World Health Organization for "broad use" in children, making it the first malaria vaccine to receive this recommendation.

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strain due to the high mortality caused by the parasite and the ease of carrying out in vitro/in vivo studies. The earliest vaccines attempted to use the parasitic

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while the control group only had an 89% incidence. The vaccine intended to cause an increased T-lymphocyte response in those exposed; this was also not observed.

4458: 1777: 1053:, was found to be a key target of the immune system's response against the parasite. Studies of blood samples from 296 mostly Kenyan children by researchers of 464:(CSP) antigen, at a higher proportion than the RTS,S vaccine. It uses the same HBsAg-linked recombinant structure, but contains no excess HBsAg. It includes the 2490: 2561: 288:

and also elicits a cellular response enabling the destruction of infected hepatocytes. The CSP vaccine presented problems in the trial stage due to its poor

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then kill any micro-organisms or foreign particles that succeed in penetration. The cell-mediated component consists of many white blood cells (such as

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In a bid to accommodate a larger group and guarantee a sustained availability for the general public, GSK applied for a marketing license with the

2141: 1984: 942:(CSP). This is the most dominant surface antigen of the initial pre-erythrocytic phase. However, problems were encountered due to low efficacy, 216:'s (WHO) goal of a malaria vaccine with at least 75% efficacy, and only the second malaria vaccine to be recommended by the WHO. In April 2023, 4691: 437: 2809: 1944: 4580: 2006: 879: 616:

toxin (A9). However, at an early stage, a complete lack of protective immunity was demonstrated in those inoculated. The study group used in

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The parasite induces two main response types from the human immune system. These are anti-parasitic immunity and anti-toxic immunity.

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is taken from immune adults, purified, and then given to individuals who have no protective immunity, some protection can be gained.

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approved the use of the R21 vaccine for use in children aged between five months and three years old. Following Ghana's decision,

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and reemerge years later to elicit new infections. Two key proteins involved in the invasion of the red blood cells (RBC) by

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has demonstrated the capability, through the development of multiple drug-resistant parasites, for evolutionary change. The

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Good M, Kemp D. "Overview of Vaccine Strategies for Malaria". In Levine MM, Kaper JB, Rappuoli R, Liu MA, Good MR (eds.).

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antigenic genes. These came from a variety of stages during the lifecycle. CSP and sporozoite surface protein 2 (called

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is the common malaria species found in India, Southeast Asia and South America. It is able to stay dormant in the

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Clyde DF (May 1975). "Immunization of man against falciparum and vivax malaria by use of attenuated sporozoites".

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Saul A. "Malaria Transmission-Blocking Vaccines". In Levine MM, Kaper JB, Rappuoli R, Liu MA, Good MR (eds.).

2946:"The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody" 5026: 4736: 4463: 4438: 4236: 639:

and produced encouraging results: 4 out of the 7 antigens produced specific antibody responses (CSP, PfSSP2,

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Foquet L, Hermsen CC, van Gemert GJ, Van Braeckel E, Weening KE, Sauerwein R, et al. (January 2014).

1264:. Over a span of 42 weeks, 24 of 26 tests on the volunteers showed that they were protected from malaria. 774:) and a cell-mediated immune response. Ideally, a vaccine would enable the development of anti-plasmodial 3679: 3381: 824: 652:

repeats of the sporozoite surface protein . Limitations of the technology exist as it contains only 20%

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Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M, et al. (November 2011).

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Douglas AD, Williams AR, Illingworth JJ, Kamuyu G, Biswas S, Goodman AL, et al. (December 2011).

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Agnandji ST, Lell B, Fernandes JF, Abossolo BP, Methogo BG, Kabwende AL, et al. (December 2012).

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The second phase of the lifecycle is the "erythrocytic" or blood phase. A vaccine here could prevent

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and QS21 (SBAS2), the vaccine gave protective immunity to 7 out of 8 volunteers when challenged with

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Burundi, Cameroon, the Democratic Republic of the Congo, Liberia, Niger, Sierra Leone, and Uganda.

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Batchelor JD, Malpede BM, Omattage NS, DeKoster GT, Henzler-Wildman KA, Tolia NH (January 2014).

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Chan JA, Howell KB, Reiling L, Ataide R, Mackintosh CL, Fowkes FJ, et al. (September 2012).

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are potential targets for drug or vaccine development. When the Duffy binding protein (DBP) of

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by x-rays. Subsequent human studies in the 1970s showed that humans could be immunized against

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Plassmeyer ML, Reiter K, Shimp RL, Kotova S, Smith PD, Hurt DE, et al. (September 2009).

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Abdulla S, Oberholzer R, Juma O, Kubhoja S, Machera F, Membi C, et al. (December 2008).

3275:"Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection" 1209: 1091: 1007: 627:

The NYVAC-Pf7 multi-stage vaccine attempted to use different technology, incorporating seven

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Screened cup of malaria-infected mosquitoes which will infect a volunteer in a clinical trial

277: 203:, known by the brand name Mosquirix. As of April 2023, the vaccine has been given to 1.5 4011: 2619:

Butler D (April 2019). "Promising malaria vaccine to be tested in first large field trial".

2562:"Nature report describes complete protection after 10 weeks with three doses of PfSPZ- CVac" 2213: 156: 5458: 5399: 5190: 4833: 4711: 4662: 4629: 4563: 4286: 3423: 3286: 3017: 2957: 2844: 2337:"Immune responses to malaria pre-erythrocytic stages: Implications for vaccine development" 1040: 1016: 1012: 813: 429: 3812:

Bejon P, Lusingu J, Olotu A, Leach A, Lievens M, Vekemans J, et al. (December 2008).

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Raj DK, Nixon CP, Nixon CE, Dvorin JD, DiPetrillo CG, Pond-Tor S, et al. (May 2014).

3197:"Red blood cell invasion by Plasmodium vivax: structural basis for DBP engagement of DARC" 2892:"Targeting protein kinases in the malaria parasite: update of an antimalarial drug target" 2163:

Datoo MS, Natama HM, Somé A, Bellamy D, Traoré O, Rouamba T, et al. (December 2022).

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and has low levels of immunogenicity. It also does not contain any immunodominant T-cell

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Please help update this article to reflect recent events or newly available information.

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Hoffman SL, Goh LM, Luke TC, Schneider I, Le TP, Doolan DL, et al. (April 2002).

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Datoo MS, Natama MH, Somé A, Traoré O, Rouamba T, Bellamy D, et al. (May 2021).

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create an immune response that protects against the harmful effects of the parasite.

770:"Anti-parasitic immunity" addresses the source; it consists of an antibody response ( 293: 5483: 3804: 3751: 2737: 5660: 5463: 5448: 5304: 5165: 5078: 4484: 4256: 4224: 4139: 4125: 4097: 4087: 4045: 3981: 3946: 3936: 3891: 3833: 3825: 3814:"Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age" 3784: 3731: 3518: 3474: 3451: 3431: 3411: 3353: 3343: 3302: 3294: 3218: 3208: 3140: 3132: 3033: 3025: 3006:"Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum" 2973: 2965: 2903: 2862: 2852: 2772: 2764: 2717: 2679: 2671: 2624: 2533: 2525: 2454: 2446: 2405: 2397: 2356: 2348: 2249: 2176: 2102: 2094: 2047: 1714: 1704: 1660: 1652: 1431: 1203: 1062: 1054: 1030: 780: 771: 571: 536:

that displayed malaria specific B cell and T cell epitopes. The particle exhibited

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endorsed the R21 vaccine against malaria, end of December 2023 it was added to the

425: 292:. RTS,S attempted to avoid these by fusing the protein with a surface antigen from 100: 5004: 2529: 1490: 853: 5644: 5468: 5073: 5031: 4922: 4902: 4872: 4855: 4781: 4771: 4701: 4640: 4636: 4585: 4428: 4291: 3675: 3213: 3170:"Scientists capture key protein structures that could aid malaria vaccine design" 2768: 2007:"Millions more children to benefit from malaria vaccine as UNICEF secures supply" 995: 974: 897: 564: 272: 264: 3382:"Immunoglobulin Therapy & Other Medical Therapies for Antibody Deficiencies" 532:

In 2015, researchers used a repetitive antigen display technology to engineer a

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Proceedings of the National Academy of Sciences of the United States of America

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by exposing them to the bites of significant numbers of irradiated mosquitos.

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One of the most successful vaccine candidates in clinical trials consists of

959: 846: 549: 457: 4850: 3941: 3348: 3298: 2857: 2802:"South African scientists discover new chemicals that kill malaria parasite" 1617: 1001:

Report of a vaccine candidate capable of neutralizing all tested strains of

5565: 5208: 5103: 5036: 4977: 4657: 4548: 4528: 4375: 4214: 3995: 3960: 3903: 3847: 3796: 3743: 3532: 3367: 3316: 3232: 3154: 3047: 2987: 2915: 2876: 2786: 2693: 2636: 2588:"SANARIA PfSPZ VACCINE AGAINST MALARIA RECEIVES FDA FAST TRACK DESIGNATION" 2547: 2468: 2419: 2370: 2190: 2116: 2059: 1774:"GSK announces EU regulatory submission of malaria vaccine candidate RTS,S" 1728: 1674: 1550: 1455: 1049:, one of the proteins known as variant surface antigens (VSAs) produced by 621: 533: 485: 453: 95: 3829: 3735: 3443: 3063:"New candidate vaccine neutralizes all tested strains of malaria parasite" 2729: 2038:

Devi S (July 2023). "12 countries to get first doses of malaria vaccine".

1709: 1602: 1491:"Malaria vaccine becomes first to achieve WHO-specified 75% efficacy goal" 1232:

by the bites of 1001–2927 mosquitoes that had been irradiated with 15,000

5352: 5342: 5203: 5009: 4897: 4865: 4791: 4653: 4544: 4536: 4315: 4251: 3486: 1890:(Press release). Homa Bay: World Health Organization. 13 September 2019. 1495: 1249: 1198: 1194: 1005:, the most deadly form of the parasite causing malaria, was published in 987: 963: 911: 893: 817: 801: 797: 793: 784: 285: 3029: 2245:"New data buoy hopes for promising malaria vaccine—but questions remain" 1436: 1140: 329:

In July 2015, Mosquirix received a positive scientific opinion from the

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providing a level of consistent future immunity against the parasite.

809: 775: 685: 559: 167: 46: 2352: 310:

malaria parasite and a portion of a hepatitis B virus plus a chemical

5527: 5098: 4971: 4540: 4325: 4176: 4161: 4027: 3717:"Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants" 3435: 3136: 1831:"First malaria vaccine receives positive scientific opinion from EMA" 1656: 1237: 970: 956: 805: 789: 3879: 3094:"Lifting malaria's deadly veil: Mystery solved in quest for vaccine" 1945:"WHO recommends groundbreaking malaria vaccine for children at risk" 827:

has a central role in generating the symptoms experienced in severe

705: 511: 5369: 5362: 5357: 5327: 5083: 5019: 5014: 3523: 3506: 1638: 1460: 1257: 1087: 657: 599: 465: 392:. The reason given is: Phase III trial data is now available here: 311: 4022: 2753:"Immunogenicity of therapeutic proteins: influence of aggregation" 1693:"A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants" 351:

The vaccine was prequalified by WHO in July 2022. In August 2022,

5088: 4532: 4082: 4068: 3698:(Press release). GlaxoSmithKline. 3 November 2009. Archived from 921:

the antibodies that could potentially elicit an immune response.

653: 555: 489: 441: 225: 192: 188: 39: 29: 3194: 3003: 2943: 2514:"Malaria vaccine based on self-assembling protein nanoparticles" 1976:"A 'Historical Event': First Malaria Vaccine Approved by W.H.O." 695: 5391: 5376: 4667: 3626: 2011: 1744:"Malaria vaccine candidate shown to prevent thousands of cases" 1245: 449: 352: 334: 3410: 554:

The PfSPZ vaccine is a candidate malaria vaccine developed by

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European and Developing Countries Clinical Trials Partnership

4268: 1915:"WHO endorses use of world's first malaria vaccine in Africa" 1690: 1241: 1067: 617: 582: 521: 342: 338: 250: 217: 200: 3714: 1422:(2022). "Malaria vaccine: WHO position paper – March 2022". 1328:. Switzerland: World Health Organization. 30 November 2023. 594:

SPf66 is a synthetic peptide based vaccine developed by the

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Schwartz L, Brown GV, Genton B, Moorthy VS (January 2012).

3329: 2751:

Ratanji KD, Derrick JP, Dearman RJ, Kimber I (April 2014).

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RTS,S was engineered using genes from the outer protein of

4037: 3922: 3880:"DNA vaccines: immunology, application, and optimization*" 2214:"Malaria Vaccine Candidate 'Impressive' in Phase III Test" 1252:

the malaria parasites so that, while they can still enter

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Good MF, Levine MA, Kaper JB, Rappuoli R, Liu MA (2004).

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In 1967, it was reported that a level of immunity to the

2334: 1681: 1551:"Ghana first to approve 'world-changer' malaria vaccine" 1216:

From 1989 to 1999, eleven volunteers recruited from the

4459:

The Global Fund to Fight AIDS, Tuberculosis and Malaria

3550: 3504: 3118: 3877: 3811: 2483:"Researcher's nanoparticle key to new malaria vaccine" 2335:

Abuga KM, Jones-Warner W, Hafalla JC (February 2021).

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the compounds would be approved as a viable treatment.

460:

as the principal investigator. The R21 vaccine uses a

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The American Journal of Tropical Medicine and Hygiene

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World Malaria Report 2023 - World Health Organization

3646: 2889: 2435:"Vaccines for preventing malaria (pre-erythrocytic)" 1193:

parasite could be given to mice by exposing them to

1112:

Increasing the potential immunity generated against

832:

difficulties in evaluating efficacy in human trials.

527: 3569: 3272: 1291:"Mosquirix: Opinion on medicine for use outside EU" 524:and R-21/Matrix-M the two approved options so far. 3856: 2269: 1864:(Press release). Wuxi: World Health Organization. 1801:"GSK aims to market world's first malaria vaccine" 1776:(Press release). GSK. 24 July 2014. Archived from 1485: 1483: 1456:"Malaria vaccine hailed as potential breakthrough" 1248:source. This level of radiation is sufficient to 5544:Cedillo v. Secretary of Health and Human Services 3248:"Antigen Discovery could advance malaria vaccine" 2281:"Ghana first to approve Oxford's malaria vaccine" 1616:. Malaria Vaccine Initiative Path. Archived from 585:was announced, scheduled to start in early 2020. 5652: 3500: 3498: 3496: 2593:. Sanaria Inc. 22 September 2016. Archived from 1544: 1542: 1540: 3574:(3rd ed.). CRC Press. pp. 1763–1790. 2890:Zhang VM, Chavchich M, Waters NC (March 2012). 2386:"Vaccines for preventing malaria (blood-stage)" 1480: 1285: 1283: 1281: 1279: 1277: 155: 1107: 977:. This approach is complicated by the lack of 438:London School of Hygiene and Tropical Medicine 4509: 4053: 3493: 2657: 2511: 2432: 2383: 1999: 1537: 696:Choosing to address the symptom or the source 394:https://doi.org/10.1016/S0140-6736(23)02511-4 3632:(3rd ed.). CRC Press. pp. 851–60. 3323: 1578: 1576: 1384: 1382: 1380: 1378: 1274: 648:. This result has warranted ongoing trials. 245:RTS,S recombinant protein viruslike particle 3878:Gurunathan S, Klinman DM, Seder RA (2000). 3854: 2830: 2664:The Cochrane Database of Systematic Reviews 2439:The Cochrane Database of Systematic Reviews 2390:The Cochrane Database of Systematic Reviews 874:Hepatocyte invasion; direct anti-sporozite 734:. Unsourced material may be challenged and 506: 4516: 4502: 4060: 4046: 2999: 2997: 2939: 2937: 1973: 3985: 3950: 3940: 3837: 3672:"Case studies: Potential malaria vaccine" 3522: 3357: 3347: 3306: 3222: 3212: 3144: 3037: 2977: 2866: 2856: 2776: 2683: 2660:"Vaccines for preventing malaria (SPf66)" 2537: 2458: 2409: 2360: 2180: 2106: 1718: 1708: 1664: 1573: 1548: 1449: 1447: 1435: 1375: 1349: 1347: 1345: 754:Learn how and when to remove this message 610:) protein covalently bound to a purified 2512:Burkhard P, Lanar DE (2 December 2015). 1741: 1355:"Q&A on RTS,S malaria vaccine - WHO" 1182: 606:(Asn-Ala-Pro15Asn-Val-Asp-Pro)2-Leu-Arg( 570:The PfSPZ vaccine candidate was granted 510: 492:provisionally approved the R21 vaccine. 414: 240: 228:provisionally approved the R21 vaccine. 4033:Gates Foundation Global Health: Malaria 3060: 2994: 2934: 2799: 1798: 5653: 3967: 3245: 3167: 3091: 2618: 2278: 1912: 1859: 1444: 1412: 1342: 1316: 468:adjuvant that is also utilized in the 355:awarded a contract to GSK to supply 18 126: 4497: 4041: 3464: 3125:The Journal of Clinical Investigation 2896:Current Topics in Medicinal Chemistry 2831:Kennedy DA, Read AF (December 2018). 2242: 1645:The Journal of Clinical Investigation 1453: 1400:from the original on 13 November 2022 1304:from the original on 23 November 2019 1034:. The earlier publication reported 896:, antibodies blocking invasion; anti 676: 588: 261:PATH Malaria Vaccine Initiative (MVI) 4364:National Malaria Eradication Program 4018:. U.S. National Library of Medicine. 3910:from the original on 20 October 2021 3588: 3176:from the original on 18 January 2014 2812:from the original on 1 February 2021 2433:Graves P, Gelband H (October 2006). 2384:Graves P, Gelband H (October 2006). 2257:from the original on 4 November 2022 2224:from the original on 22 January 2023 2211: 2129: 2037: 1894:from the original on 22 October 2019 1880: 1868:from the original on 31 January 2022 1853: 1811:from the original on 18 January 2016 1135: 840: 732:adding citations to reliable sources 699: 581:In April 2019, a phase III trial in 374: 231: 99: 4419:Bill & Melinda Gates Foundation 3818:The New England Journal of Medicine 3761:from the original on 9 October 2021 3724:The New England Journal of Medicine 3336:The Journal of Biological Chemistry 3100:from the original on 18 August 2012 2564:(Press release). 15 February 2017. 2493:from the original on 11 August 2016 2019:from the original on 2 January 2023 1987:from the original on 7 October 2021 1955:from the original on 7 October 2021 1925:from the original on 7 October 2021 1841:from the original on 3 October 2018 1697:The New England Journal of Medicine 1218:United States Public Health Service 13: 5571:Eradication of infectious diseases 5328:Androvax (androstenedione albumin) 3543: 3511:The Journal of Infectious Diseases 3392:from the original on 15 March 2020 2658:Graves P, Gelband H (April 2006). 2568:from the original on 23 April 2021 2291:from the original on 13 April 2023 2144:from the original on 15 April 2023 1561:from the original on 13 April 2023 1468:from the original on 24 April 2021 1081:Washington University in St. Louis 994:Another approach is to target the 973:multiplication or the invasion of 14: 5677: 5161:Respiratory syncytial virus (RSV) 4004: 3254:from the original on 4 March 2016 1503:from the original on 27 July 2021 1011:by a team of scientists from the 852:Potential vaccine targets in the 668: 528:Nanoparticle enhancement of RTS,S 269:Bill and Melinda Gates Foundation 197:mosquito-borne infectious disease 5638: 5550:Alternative vaccination schedule 4525:Artificial induction of immunity 4480: 4479: 4449:African Leaders Malaria Alliance 4444:South African Malaria Initiative 3970:"Malaria: new vaccines for old?" 3896:10.1146/annurev.immunol.18.1.927 3678:. 21 August 2009. Archived from 3607: 3555:. New York, N.Y: Marcel Dekker. 1862:"Letter to partners – June 2019" 1139: 704: 543: 434:Kenya Medical Research Institute 419:Comparison between RTS,S and R21 379: 4302:Malaria antigen detection tests 3458: 3404: 3374: 3266: 3239: 3188: 3161: 3112: 3085: 3069:. FierceBiotech. Archived from 3054: 2883: 2824: 2793: 2744: 2700: 2651: 2612: 2580: 2554: 2505: 2475: 2426: 2377: 2328: 2303: 2236: 2205: 2169:The Lancet. Infectious Diseases 2156: 2123: 2074: 2031: 1974:Mandavilli A (6 October 2021). 1967: 1937: 1906: 1823: 1792: 1766: 1754:from the original on 6 May 2016 1735: 1632: 1026:Wellcome Trust Sanger Institute 370: 5382:Ovandrotone albumin (Fecundin) 4386:Malaria in Mandatory Palestine 3061:Martino M (21 December 2011). 2137:Science Translational Medicine 1515: 1122:recombinant antigenic proteins 962:that can destroy the infected 488:. Following Ghana's decision, 341:, and on 13 September 2019 in 1: 4918:Group B streptococcal disease 4737:Vaccines for Children Program 4464:Medicines for Malaria Venture 4439:African Malaria Network Trust 3863:. 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Anti-host 825:tumor necrosis factor-alpha 558:using radiation-attenuated 275:vaccine, consisting of the 10: 5682: 4414:Against Malaria Foundation 4023:Malaria Vaccine Initiative 3987:10.1016/j.cell.2006.02.011 3968:Waters A (February 2006). 3092:Parish T (2 August 2012). 2908:10.2174/156802612799362922 2629:10.1038/d41586-019-01232-4 2487:Research & Development 2279:Grover N (12 April 2023). 2212:Hein I (3 November 2022). 1131: 1019:, targeting a full-length 844: 547: 362:As of April 2023, 1.5 248: 134:Approved in Ghana, Nigeria 5589: 5558: 5497: 5429: 5320: 5292: 5259: 4933: 4764: 4757: 4676: 4604: 4556: 4477: 4454:Amazon Malaria Initiative 4401: 4336: 4279: 4197: 4075: 3479:10.4269/ajtmh.1975.24.397 2676:10.1002/14651858.CD005966 2518:Expert Review of Vaccines 2451:10.1002/14651858.CD006198 2402:10.1002/14651858.CD006199 1949:World Health Organization 1860:Alonso P (19 June 2019). 1835:European Medicines Agency 1454:Roxby P (23 April 2021). 1420:World Health Organization 1360:World Health Organization 1296:European Medicines Agency 884:Direct anti-hepatozoite. 388:This section needs to be 331:European Medicines Agency 324:European Medicines Agency 214:World Health Organization 166: 146: 141: 116: 111: 86: 72: 62: 57: 45: 35: 28: 5666:Protein subunit vaccines 4913:Clostridioides difficile 4381:Malaria in the Caribbean 4230:Sterile insect technique 3246:Mullin E (27 May 2014). 2130:Lowe D (23 April 2021). 1126:circumsporozoite protein 940:circumsporozoite protein 620:had an 82% incidence of 507:Agents under development 481:Food and Drugs Authority 470:Novavax COVID-19 vaccine 462:circumsporozoite protein 446:Serum Institute of India 282:circumsporozoite protein 236: 222:Food and Drugs Authority 5171:Tick-borne encephalitis 4434:Africa Fighting Malaria 4280:Diagnosis and treatment 3942:10.1186/1475-2875-11-11 3649:New Generation Vaccines 3630:New generation vaccines 3610:New Generation Vaccines 3572:New Generation Vaccines 3553:New Generation Vaccines 3349:10.1074/jbc.M109.013706 3299:10.1126/science.1254417 2858:10.1073/pnas.1717159115 1228:were immunized against 1175:Research shows that if 1086:Antibodies against the 259:RTS,S was developed by 16:Vaccine against malaria 5581:List of vaccine topics 4581:Mathematical modelling 4198:Control and prevention 613:Pseudomonas aeruginosa 596:Manuel Elkin Patarroyo 572:fast track designation 520:being developed, with 516: 420: 337:, on 30 April 2019 in 246: 5576:Vaccinate Your Family 5027:Japanese encephalitis 4391:Malaria Atlas Project 3830:10.1056/NEJMoa0807381 3736:10.1056/NEJMoa0807773 2950:Nature Communications 1837:(EMA). 24 July 2015. 1710:10.1056/NEJMoa1208394 1230:Plasmodium falciparum 1210:Plasmodium falciparum 1183:Irradiated mosquitoes 1096:Plasmodium falciparum 1092:Rhode Island Hospital 1051:Plasmodium falciparum 1008:Nature Communications 1003:Plasmodium falciparum 936:Plasmodium falciparum 900:, anti-soluble toxin 856:(Doolan and Hoffman) 514: 418: 278:Plasmodium falciparum 244: 5459:John Franklin Enders 4287:Diagnosis of malaria 4103:Pregnancy-associated 3096:. Burnet Institute. 2489:. 4 September 2014. 2093:(10287): 1809–1818. 1041:University of Oxford 1017:viral vector vaccine 1013:University of Oxford 889:Asexual erythrocytic 814:natural killer cells 728:improve this section 495:In October 2023 the 430:University of Oxford 4645:Virus-like particle 4569:Vaccine ingredients 4344:Diseases of poverty 4337:Society and malaria 4247:Sickle-cell anaemia 4220:Malaria prophylaxis 4028:Malaria vaccines UK 3702:on 10 November 2009 3428:1967Natur.216..160N 3291:2014Sci...344..871R 3030:10.1038/nature10606 3022:2011Natur.480..534C 2962:2011NatCo...2..601D 2849:2018PNAS..11512878K 2843:(51): 12878–12886. 2341:Parasite Immunology 857: 578:in September 2016. 30:Vaccine description 25: 5616:Never to phase III 5415:Hexavalent vaccine 5229:Epstein–Barr virus 5124:Oxford–AstraZeneca 4817:NmVac4-A/C/Y/W-135 4424:Imagine No Malaria 4409:Malaria Consortium 4354:History of malaria 4237:Genetic resistance 4162:Anopheles mosquito 4012:"Malaria Vaccines" 2970:10.1038/ncomms1615 2600:on 23 October 2016 2015:. 16 August 2022. 1980:The New York Times 1780:on 4 December 2016 1614:malariavaccine.org 1226:United States Navy 1222:United States Army 1190:Plasmodium berghei 1151:. You can help by 851: 677:Parasite diversity 589:Other developments 517: 421: 247: 21: 5626: 5625: 5538:Vaccines and SIDS 5425: 5424: 5199:Hepatitis A and B 5175:Varicella zoster 4637:Subunit/component 4491: 4490: 4371:World Malaria Day 3870:978-0-632-05902-7 3783:(9598): 1543–51. 3674:(Press release). 3667:The Jordan Report 3658:978-0-429-15186-6 3639:978-0-429-15186-6 3619:978-0-429-15186-6 3600:978-0-429-15186-6 3581:978-0-429-15186-6 3562:978-0-8247-4071-9 3067:fiercebiotech.com 2716:(9029): 701–707. 2353:10.1111/pim.12795 2175:(12): 1728–1736. 1947:(Press release). 1833:(Press release). 1499:. 23 April 2021. 1335:978-92-4-006489-8 1169: 1168: 1103:and RBC invasion. 918: 917: 854:malaria lifecycle 841:Potential targets 764: 763: 756: 413: 412: 294:hepatitis B virus 232:Approved vaccines 182: 181: 130: 5673: 5643: 5642: 5641: 5634: 5517:MMR autism fraud 5464:Maurice Hilleman 5449:Hilary Koprowski 4762: 4761: 4518: 4511: 4504: 4495: 4494: 4483: 4482: 4257:G6PDH deficiency 4225:Mosquito control 4098:Blackwater fever 4062: 4055: 4048: 4039: 4038: 4019: 3999: 3989: 3964: 3954: 3944: 3919: 3917: 3915: 3874: 3862: 3851: 3841: 3808: 3770: 3768: 3766: 3760: 3721: 3711: 3709: 3707: 3691: 3689: 3687: 3662: 3643: 3623: 3604: 3585: 3566: 3537: 3536: 3526: 3502: 3491: 3490: 3462: 3456: 3455: 3436:10.1038/216160a0 3408: 3402: 3401: 3399: 3397: 3378: 3372: 3371: 3361: 3351: 3342:(39): 26951–63. 3327: 3321: 3320: 3310: 3270: 3264: 3263: 3261: 3259: 3243: 3237: 3236: 3226: 3216: 3192: 3186: 3185: 3183: 3181: 3165: 3159: 3158: 3148: 3137:10.1172/JCI62182 3116: 3110: 3109: 3107: 3105: 3089: 3083: 3082: 3080: 3078: 3073:on 20 April 2012 3058: 3052: 3051: 3041: 3001: 2992: 2991: 2981: 2941: 2932: 2931: 2929: 2927: 2918:. 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4522: 4492: 4487: 4473: 4429:Malaria No More 4397: 4332: 4292:Malaria culture 4275: 4264:Malaria vaccine 4193: 4071: 4066: 4010: 4007: 4002: 3929:Malaria Journal 3913: 3911: 3871: 3824:(24): 2521–32. 3764: 3762: 3758: 3730:(24): 2533–44. 3719: 3705: 3703: 3694: 3685: 3683: 3682:on 27 July 2009 3676:GlaxoSmithKline 3670: 3659: 3640: 3620: 3601: 3582: 3563: 3546: 3544:Further reading 3541: 3540: 3503: 3494: 3463: 3459: 3422:(5111): 160–2. 3409: 3405: 3395: 3393: 3380: 3379: 3375: 3328: 3324: 3285:(6186): 871–7. 3271: 3267: 3257: 3255: 3244: 3240: 3207:(1): e1003869. 3193: 3189: 3179: 3177: 3166: 3162: 3117: 3113: 3103: 3101: 3090: 3086: 3076: 3074: 3059: 3055: 3016:(7378): 534–7. 3002: 2995: 2942: 2935: 2925: 2923: 2888: 2884: 2829: 2825: 2815: 2813: 2798: 2794: 2749: 2745: 2705: 2701: 2670:(2): CD005966. 2656: 2652: 2617: 2613: 2603: 2601: 2597: 2590: 2586: 2585: 2581: 2571: 2569: 2560: 2559: 2555: 2510: 2506: 2496: 2494: 2481: 2480: 2476: 2445:(4): CD006198. 2431: 2427: 2396:(4): CD006199. 2382: 2378: 2333: 2329: 2319: 2317: 2309: 2308: 2304: 2294: 2292: 2277: 2270: 2260: 2258: 2241: 2237: 2227: 2225: 2210: 2206: 2161: 2157: 2147: 2145: 2128: 2124: 2079: 2075: 2036: 2032: 2022: 2020: 2005: 2004: 2000: 1990: 1988: 1972: 1968: 1958: 1956: 1943: 1942: 1938: 1928: 1926: 1911: 1907: 1897: 1895: 1886: 1885: 1881: 1871: 1869: 1858: 1854: 1844: 1842: 1829: 1828: 1824: 1814: 1812: 1797: 1793: 1783: 1781: 1772: 1771: 1767: 1757: 1755: 1740: 1736: 1703:(24): 2284–95. 1689: 1682: 1637: 1633: 1623: 1621: 1608: 1607: 1603: 1593: 1591: 1590:. 18 April 2023 1582: 1581: 1574: 1564: 1562: 1547: 1538: 1528: 1526: 1521: 1520: 1516: 1506: 1504: 1489: 1488: 1481: 1471: 1469: 1452: 1445: 1417: 1413: 1403: 1401: 1396:. 13 May 2022. 1388: 1387: 1376: 1366: 1364: 1363:. 19 April 2023 1353: 1352: 1343: 1336: 1322: 1321: 1317: 1307: 1305: 1289: 1288: 1275: 1270: 1262:red blood cells 1185: 1165: 1159: 1156: 1149:needs expansion 1134: 1110: 1028:, published in 996:protein kinases 975:red blood cells 898:receptor ligand 849: 843: 760: 749: 743: 740: 725: 709: 698: 679: 671: 591: 565:liquid nitrogen 552: 546: 530: 509: 409: 403: 400: 397: 384: 380: 373: 363: 356: 265:GlaxoSmithKline 253: 239: 234: 204: 178: 162: 137: 107: 75: 52:Protein subunit 23:Malaria vaccine 17: 12: 11: 5: 5679: 5669: 5668: 5663: 5648: 5647: 5624: 5623: 5620: 5619: 5618: 5617: 5614: 5603: 5597: 5591: 5590: 5587: 5586: 5584: 5583: 5578: 5573: 5568: 5562: 5560: 5556: 5555: 5553: 5552: 5547: 5540: 5535: 5530: 5525: 5520: 5507: 5501: 5499: 5495: 5494: 5492: 5491: 5486: 5484:Katalin Karikó 5481: 5476: 5471: 5466: 5461: 5456: 5451: 5446: 5441: 5435: 5433: 5427: 5426: 5423: 5422: 5420: 5419: 5418: 5417: 5412: 5407: 5402: 5394: 5389: 5384: 5379: 5374: 5373: 5372: 5367: 5366: 5365: 5360: 5350: 5345: 5340: 5330: 5324: 5322: 5318: 5317: 5315: 5314: 5313: 5312: 5307: 5298: 5296: 5290: 5289: 5287: 5286: 5285: 5284: 5276: 5275: 5274: 5263: 5261: 5257: 5256: 5254: 5253: 5252: 5251: 5246: 5241: 5239:Herpes simplex 5236: 5231: 5226: 5221: 5213: 5212: 5211: 5206: 5201: 5193: 5188: 5187: 5186: 5181: 5173: 5168: 5163: 5158: 5157: 5156: 5151: 5146: 5141: 5139:Sinopharm BIBP 5136: 5131: 5126: 5121: 5116: 5111: 5106: 5101: 5096: 5091: 5089:Bharat Biotech 5086: 5076: 5071: 5066: 5061: 5060: 5059: 5054: 5044: 5039: 5034: 5029: 5024: 5023: 5022: 5017: 5007: 5002: 4997: 4992: 4987: 4986: 4985: 4980: 4975: 4960: 4959: 4958: 4948: 4943: 4937: 4935: 4931: 4930: 4928: 4927: 4926: 4925: 4920: 4915: 4907: 4906: 4905: 4900: 4892: 4887: 4886: 4885: 4880: 4870: 4869: 4868: 4858: 4853: 4848: 4847: 4846: 4841: 4831: 4826: 4821: 4820: 4819: 4814: 4804: 4799: 4794: 4789: 4784: 4779: 4774: 4768: 4766: 4759: 4755: 4754: 4752: 4751: 4750: 4749: 4744: 4739: 4734: 4729: 4721: 4720: 4719: 4717:Vaccine injury 4714: 4709: 4704: 4699: 4694: 4689: 4680: 4678: 4677:Administration 4674: 4673: 4671: 4670: 4665: 4660: 4651: 4634: 4633: 4632: 4627: 4619: 4614: 4608: 4606: 4602: 4601: 4599: 4598: 4593: 4588: 4583: 4578: 4577: 4576: 4566: 4560: 4558: 4554: 4553: 4521: 4520: 4513: 4506: 4498: 4489: 4488: 4478: 4475: 4474: 4472: 4471: 4466: 4461: 4456: 4451: 4446: 4441: 4436: 4431: 4426: 4421: 4416: 4411: 4405: 4403: 4399: 4398: 4396: 4395: 4394: 4393: 4388: 4383: 4373: 4368: 4367: 4366: 4361: 4351: 4346: 4340: 4338: 4334: 4333: 4331: 4330: 4329: 4328: 4323: 4318: 4307: 4306: 4305: 4304: 4299: 4294: 4283: 4281: 4277: 4276: 4274: 4273: 4272: 4271: 4261: 4260: 4259: 4254: 4249: 4244: 4234: 4233: 4232: 4227: 4222: 4217: 4212: 4201: 4199: 4195: 4194: 4192: 4191: 4190: 4189: 4184: 4179: 4174: 4164: 4159: 4158: 4157: 4150: 4143: 4136: 4129: 4122: 4117: 4107: 4106: 4105: 4100: 4095: 4090: 4079: 4077: 4073: 4072: 4065: 4064: 4057: 4050: 4042: 4036: 4035: 4030: 4025: 4020: 4006: 4005:External links 4003: 4001: 4000: 3965: 3920: 3875: 3869: 3852: 3809: 3771: 3712: 3692: 3668: 3665: 3664: 3663: 3657: 3644: 3638: 3624: 3618: 3605: 3599: 3586: 3580: 3561: 3547: 3545: 3542: 3539: 3538: 3524:10.1086/339409 3517:(8): 1155–64. 3492: 3473:(3): 397–401. 3457: 3412:Nussenzweig RS 3403: 3373: 3322: 3265: 3238: 3201:PLOS Pathogens 3187: 3160: 3131:(9): 3227–38. 3111: 3084: 3053: 2993: 2933: 2922:on 30 May 2013 2882: 2823: 2792: 2743: 2699: 2650: 2611: 2579: 2553: 2524:(12): 1525–7. 2504: 2474: 2425: 2376: 2327: 2302: 2268: 2235: 2204: 2155: 2122: 2073: 2046:(10397): 172. 2030: 1998: 1966: 1936: 1905: 1879: 1852: 1822: 1791: 1765: 1748:www.gizmag.com 1734: 1680: 1631: 1601: 1572: 1536: 1514: 1479: 1443: 1411: 1374: 1341: 1334: 1315: 1272: 1271: 1269: 1266: 1197:that had been 1184: 1181: 1177:immunoglobulin 1167: 1166: 1146: 1144: 1133: 1130: 1109: 1106: 1105: 1104: 1084: 1059: 1044: 1015:in 2011. The 999: 992: 983: 967: 948:immunogenicity 944:reactogenicity 916: 915: 908: 902: 901: 890: 886: 885: 882: 876: 875: 872: 866: 865: 862: 861:Parasite stage 842: 839: 834: 833: 821: 762: 761: 712: 710: 703: 697: 694: 678: 675: 670: 669:Considerations 667: 666: 665: 661: 649: 637:rhesus monkeys 625: 603: 590: 587: 548:Main article: 545: 542: 529: 526: 508: 505: 411: 410: 387: 385: 378: 372: 369: 302:P. falciparum. 290:immunogenicity 249:Main article: 238: 235: 233: 230: 180: 179: 177: 176: 172: 170: 164: 163: 161: 160: 152: 150: 144: 143: 139: 138: 136: 135: 132: 122: 120: 114: 113: 109: 108: 106: 105: 92: 90: 84: 83: 78: 76:administration 70: 69: 66: 60: 59: 55: 54: 49: 43: 42: 37: 33: 32: 15: 9: 6: 4: 3: 2: 5678: 5667: 5664: 5662: 5659: 5658: 5656: 5646: 5636: 5635: 5632: 5615: 5613: 5610: 5609: 5607: 5604: 5601: 5598: 5596: 5593: 5592: 5588: 5582: 5579: 5577: 5574: 5572: 5569: 5567: 5564: 5563: 5561: 5557: 5551: 5548: 5546: 5545: 5541: 5539: 5536: 5534: 5531: 5529: 5526: 5524: 5521: 5518: 5516: 5511: 5508: 5506: 5503: 5502: 5500: 5496: 5490: 5489:Drew Weissman 5487: 5485: 5482: 5480: 5477: 5475: 5474:H. Fred Clark 5472: 5470: 5467: 5465: 5462: 5460: 5457: 5455: 5452: 5450: 5447: 5445: 5444:Louis Pasteur 5442: 5440: 5439:Edward Jenner 5437: 5436: 5434: 5428: 5416: 5413: 5411: 5410:DTwP-HepB-Hib 5408: 5406: 5405:DTaP-IPV-HepB 5403: 5401: 5398: 5397: 5396:combination: 5395: 5393: 5390: 5388: 5385: 5383: 5380: 5378: 5375: 5371: 5368: 5364: 5361: 5359: 5356: 5355: 5354: 5351: 5349: 5346: 5344: 5341: 5339: 5336: 5335: 5334: 5331: 5329: 5326: 5325: 5323: 5319: 5311: 5308: 5306: 5303: 5302: 5300: 5299: 5297: 5295: 5294:Helminthiasis 5291: 5283: 5280: 5279: 5277: 5273: 5270: 5269: 5268: 5265: 5264: 5262: 5258: 5250: 5247: 5245: 5242: 5240: 5237: 5235: 5232: 5230: 5227: 5225: 5222: 5220: 5217: 5216: 5214: 5210: 5207: 5205: 5202: 5200: 5197: 5196: 5195:combination: 5194: 5192: 5189: 5185: 5182: 5180: 5177: 5176: 5174: 5172: 5169: 5167: 5164: 5162: 5159: 5155: 5152: 5150: 5147: 5145: 5142: 5140: 5137: 5135: 5132: 5130: 5127: 5125: 5122: 5120: 5117: 5115: 5112: 5110: 5107: 5105: 5102: 5100: 5097: 5095: 5092: 5090: 5087: 5085: 5082: 5081: 5080: 5077: 5075: 5072: 5070: 5067: 5065: 5062: 5058: 5055: 5053: 5050: 5049: 5048: 5045: 5043: 5040: 5038: 5035: 5033: 5030: 5028: 5025: 5021: 5018: 5016: 5013: 5012: 5011: 5008: 5006: 5003: 5001: 4998: 4996: 4993: 4991: 4988: 4984: 4981: 4979: 4976: 4973: 4969: 4966: 4965: 4964: 4961: 4957: 4954: 4953: 4952: 4949: 4947: 4944: 4942: 4939: 4938: 4936: 4932: 4924: 4921: 4919: 4916: 4914: 4911: 4910: 4908: 4904: 4901: 4899: 4898:DPT/DTwP/DTaP 4896: 4895: 4894:combination: 4893: 4891: 4888: 4884: 4881: 4879: 4876: 4875: 4874: 4871: 4867: 4864: 4863: 4862: 4859: 4857: 4854: 4852: 4849: 4845: 4842: 4840: 4837: 4836: 4835: 4832: 4830: 4827: 4825: 4822: 4818: 4815: 4813: 4810: 4809: 4808: 4807:Meningococcus 4805: 4803: 4800: 4798: 4797:Leptospirosis 4795: 4793: 4790: 4788: 4785: 4783: 4780: 4778: 4775: 4773: 4770: 4769: 4767: 4763: 4760: 4756: 4748: 4745: 4743: 4740: 4738: 4735: 4733: 4732:Vaccine court 4730: 4728: 4725: 4724: 4722: 4718: 4715: 4713: 4710: 4708: 4705: 4703: 4700: 4698: 4695: 4693: 4690: 4688: 4687:GAVI Alliance 4685: 4684: 4682: 4681: 4679: 4675: 4669: 4666: 4664: 4661: 4659: 4655: 4652: 4650: 4646: 4642: 4638: 4635: 4631: 4628: 4626: 4623: 4622: 4620: 4618: 4615: 4613: 4610: 4609: 4607: 4603: 4597: 4594: 4592: 4589: 4587: 4584: 4582: 4579: 4575: 4572: 4571: 4570: 4567: 4565: 4562: 4561: 4559: 4555: 4550: 4546: 4542: 4538: 4534: 4530: 4526: 4519: 4514: 4512: 4507: 4505: 4500: 4499: 4496: 4486: 4476: 4470: 4467: 4465: 4462: 4460: 4457: 4455: 4452: 4450: 4447: 4445: 4442: 4440: 4437: 4435: 4432: 4430: 4427: 4425: 4422: 4420: 4417: 4415: 4412: 4410: 4407: 4406: 4404: 4402:Organisations 4400: 4392: 4389: 4387: 4384: 4382: 4379: 4378: 4377: 4374: 4372: 4369: 4365: 4362: 4360: 4357: 4356: 4355: 4352: 4350: 4347: 4345: 4342: 4341: 4339: 4335: 4327: 4324: 4322: 4319: 4317: 4314: 4313: 4312: 4311:Antimalarials 4309: 4308: 4303: 4300: 4298: 4295: 4293: 4290: 4289: 4288: 4285: 4284: 4282: 4278: 4270: 4267: 4266: 4265: 4262: 4258: 4255: 4253: 4250: 4248: 4245: 4243: 4242:Duffy antigen 4240: 4239: 4238: 4235: 4231: 4228: 4226: 4223: 4221: 4218: 4216: 4213: 4211: 4208: 4207: 4206: 4205:Public health 4203: 4202: 4200: 4196: 4188: 4185: 4183: 4180: 4178: 4175: 4173: 4170: 4169: 4168: 4165: 4163: 4160: 4156: 4155: 4151: 4149: 4148: 4144: 4142: 4141: 4137: 4135: 4134: 4130: 4128: 4127: 4123: 4121: 4118: 4116: 4113: 4112: 4111: 4108: 4104: 4101: 4099: 4096: 4094: 4093:Quartan fever 4091: 4089: 4086: 4085: 4084: 4081: 4080: 4078: 4074: 4070: 4063: 4058: 4056: 4051: 4049: 4044: 4043: 4040: 4034: 4031: 4029: 4026: 4024: 4021: 4017: 4013: 4009: 4008: 3997: 3993: 3988: 3983: 3980:(4): 689–93. 3979: 3975: 3971: 3966: 3962: 3958: 3953: 3948: 3943: 3938: 3934: 3930: 3926: 3921: 3909: 3905: 3901: 3897: 3893: 3889: 3885: 3881: 3876: 3872: 3866: 3861: 3860: 3853: 3849: 3845: 3840: 3835: 3831: 3827: 3823: 3819: 3815: 3810: 3806: 3802: 3798: 3794: 3790: 3786: 3782: 3778: 3772: 3757: 3753: 3749: 3745: 3741: 3737: 3733: 3729: 3725: 3718: 3713: 3701: 3697: 3693: 3681: 3677: 3673: 3669: 3666: 3660: 3654: 3650: 3645: 3641: 3635: 3631: 3625: 3621: 3615: 3611: 3606: 3602: 3596: 3592: 3587: 3583: 3577: 3573: 3568: 3567: 3564: 3558: 3554: 3549: 3548: 3534: 3530: 3525: 3520: 3516: 3512: 3508: 3501: 3499: 3497: 3488: 3484: 3480: 3476: 3472: 3468: 3461: 3453: 3449: 3445: 3441: 3437: 3433: 3429: 3425: 3421: 3417: 3413: 3407: 3391: 3387: 3383: 3377: 3369: 3365: 3360: 3355: 3350: 3345: 3341: 3337: 3333: 3326: 3318: 3314: 3309: 3304: 3300: 3296: 3292: 3288: 3284: 3280: 3276: 3269: 3253: 3249: 3242: 3234: 3230: 3225: 3220: 3215: 3210: 3206: 3202: 3198: 3191: 3175: 3171: 3164: 3156: 3152: 3147: 3142: 3138: 3134: 3130: 3126: 3122: 3115: 3099: 3095: 3088: 3072: 3068: 3064: 3057: 3049: 3045: 3040: 3035: 3031: 3027: 3023: 3019: 3015: 3011: 3007: 3000: 2998: 2989: 2985: 2980: 2975: 2971: 2967: 2963: 2959: 2955: 2951: 2947: 2940: 2938: 2921: 2917: 2913: 2909: 2905: 2902:(5): 456–72. 2901: 2897: 2893: 2886: 2878: 2874: 2869: 2864: 2859: 2854: 2850: 2846: 2842: 2838: 2834: 2827: 2811: 2807: 2803: 2796: 2788: 2784: 2779: 2774: 2770: 2766: 2763:(2): 99–109. 2762: 2758: 2754: 2747: 2739: 2735: 2731: 2727: 2723: 2719: 2715: 2711: 2703: 2695: 2691: 2686: 2681: 2677: 2673: 2669: 2665: 2661: 2654: 2646: 2642: 2638: 2634: 2630: 2626: 2622: 2615: 2596: 2589: 2583: 2567: 2563: 2557: 2549: 2545: 2540: 2535: 2531: 2527: 2523: 2519: 2515: 2508: 2492: 2488: 2484: 2478: 2470: 2466: 2461: 2456: 2452: 2448: 2444: 2440: 2436: 2429: 2421: 2417: 2412: 2407: 2403: 2399: 2395: 2391: 2387: 2380: 2372: 2368: 2363: 2358: 2354: 2350: 2347:(2): e12795. 2346: 2342: 2338: 2331: 2316: 2312: 2306: 2290: 2286: 2282: 2275: 2273: 2256: 2252: 2251: 2246: 2239: 2223: 2219: 2218:MedPage Today 2215: 2208: 2200: 2196: 2192: 2188: 2183: 2178: 2174: 2170: 2166: 2159: 2143: 2139: 2138: 2133: 2126: 2118: 2114: 2109: 2104: 2100: 2096: 2092: 2088: 2084: 2077: 2069: 2065: 2061: 2057: 2053: 2049: 2045: 2041: 2034: 2018: 2014: 2013: 2008: 2002: 1986: 1982: 1981: 1977: 1970: 1954: 1950: 1946: 1940: 1924: 1920: 1916: 1909: 1893: 1889: 1883: 1867: 1863: 1856: 1840: 1836: 1832: 1826: 1810: 1806: 1802: 1795: 1779: 1775: 1769: 1753: 1749: 1745: 1738: 1730: 1726: 1721: 1716: 1711: 1706: 1702: 1698: 1694: 1687: 1685: 1676: 1672: 1667: 1662: 1658: 1654: 1650: 1646: 1642: 1635: 1619: 1615: 1611: 1605: 1589: 1585: 1579: 1577: 1560: 1556: 1552: 1545: 1543: 1541: 1524: 1518: 1502: 1498: 1497: 1492: 1486: 1484: 1467: 1463: 1462: 1457: 1450: 1448: 1438: 1433: 1429: 1425: 1421: 1415: 1399: 1395: 1391: 1385: 1383: 1381: 1379: 1362: 1361: 1356: 1350: 1348: 1346: 1337: 1331: 1327: 1326: 1319: 1303: 1299: 1297: 1292: 1286: 1284: 1282: 1280: 1278: 1273: 1265: 1263: 1259: 1255: 1254:hepatic cells 1251: 1247: 1243: 1239: 1235: 1231: 1227: 1223: 1219: 1214: 1212: 1211: 1206: 1205: 1200: 1196: 1192: 1191: 1180: 1178: 1173: 1163: 1160:February 2018 1154: 1150: 1147:This section 1145: 1142: 1138: 1137: 1129: 1127: 1123: 1118: 1115: 1102: 1097: 1093: 1089: 1085: 1082: 1077: 1073: 1069: 1065: 1064: 1060: 1056: 1052: 1048: 1045: 1042: 1037: 1036:P. falciparum 1033: 1032: 1027: 1022: 1021:P. falciparum 1018: 1014: 1010: 1009: 1004: 1000: 997: 993: 989: 984: 980: 976: 972: 968: 965: 961: 960:T-lymphocytes 958: 953: 952: 951: 949: 945: 941: 937: 931: 928: 927:P. falciparum 922: 913: 909: 907: 904: 903: 899: 895: 891: 888: 887: 883: 881: 878: 877: 873: 871: 868: 867: 863: 860: 859: 855: 848: 847:PfSPZ Vaccine 838: 830: 829:P. falciparum 826: 822: 819: 815: 811: 807: 803: 799: 795: 791: 786: 782: 777: 773: 769: 768: 767: 758: 755: 747: 737: 733: 729: 723: 722: 718: 713:This section 711: 707: 702: 701: 693: 690: 688: 683: 682:P. falciparum 674: 662: 659: 655: 650: 647: 646:P. falciparum 642: 638: 634: 630: 629:P. falciparum 626: 623: 619: 615: 614: 609: 604: 601: 597: 593: 592: 586: 584: 579: 577: 573: 568: 566: 561: 557: 551: 550:PfSPZ Vaccine 544:PfSPZ vaccine 541: 539: 535: 525: 523: 513: 504: 502: 498: 493: 491: 487: 482: 477: 473: 471: 467: 463: 459: 458:Halidou Tinto 455: 451: 447: 443: 439: 435: 431: 427: 417: 407: 395: 391: 386: 377: 376: 368: 360: 354: 349: 346: 344: 340: 336: 332: 327: 325: 320: 316: 313: 309: 308:P. falciparum 304: 303: 299: 295: 291: 287: 283: 280: 279: 274: 270: 266: 262: 257: 252: 243: 229: 227: 223: 219: 215: 209: 202: 198: 194: 191:that prevent 190: 186: 174: 173: 171: 169: 165: 158: 154: 153: 151: 149: 145: 140: 133: 131: Rx-only 124: 123: 121: 119: 115: 110: 102: 97: 94: 93: 91: 89: 85: 82: 81:Intramuscular 79: 77: 71: 67: 65: 61: 58:Clinical data 56: 53: 50: 48: 44: 41: 38: 34: 31: 27: 19: 5566:Epidemiology 5542: 5514: 5400:DTaP-IPV/Hib 5266: 5191:Yellow fever 5104:EpiVacCorona 4861:Tuberculosis 4834:Pneumococcal 4802:Lyme disease 4630:Heterologous 4529:Immunization 4376:Epidemiology 4263: 4215:Mosquito net 4152: 4145: 4138: 4131: 4124: 4015: 3977: 3973: 3932: 3928: 3912:. 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