Advertisement

Malaria Vaccines

  • Christopher V. PloweEmail author
Chapter

Abstract

Vaccines are the most powerful public health tools mankind has created, and research toward malaria vaccines began not long after the parasite responsible for this global killer was discovered and its life cycle described more than 100 years ago. But parasites are bigger, more complicated, and wilier than the viruses and bacteria that have been conquered or controlled with vaccines, and a malaria vaccine has remained elusive. High levels of protective efficacy were achieved in crude early experiments in animals and humans using weakened whole parasites, but the results of more sophisticated modern approaches using molecular techniques have ranged from modest success to abject failure. A subunit recombinant protein vaccine that affords in the neighborhood of 25–50% protective efficacy against malaria is in the late stages of clinical evaluation in Africa. Incremental improvements on this successful vaccine are possible and worth pursuing, but the best hope for a malaria vaccine that would improve prospects for malaria may lie with the use of attenuated whole parasites and powerful immune-boosting adjuvants.

Keywords

Severe Malaria Clinical Malaria Malaria Vaccine Placental Malaria Malaria Vaccine Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Glossary

Adjuvant

A substance added to a vaccine to stimulate a stronger or more effective immune response.

Blood stage

The stage of the malaria parasite life cycle responsible for clinical symptoms. Vaccines that target the blood stage are intended to prevent disease and death, but they do not prevent infection and may not affect malaria transmission.

Challenge trial

Small experimental Phase 1/2 clinical trial in which healthy volunteers receive a malaria vaccine and are exposed to the bites of malaria-infected mosquitoes or injected with malaria parasites under carefully controlled conditions.

Immunogenicity

The ability of a vaccine to produce specific immune responses (usually antibodies) that recognize the vaccine antigen.

Pre-erythrocytic

Stages of the malaria parasite that are injected by a mosquito and develop in the liver before emerging into the blood where they can cause symptoms. Vaccines targeting pre-erythrocytic stages are intended to prevent infection altogether and, if highly effective, would also prevent disease and block transmission.

Sexual stage

The male and female forms of malaria parasites that are responsible for transmission through mosquitoes. Vaccines directed against sexual stages are intended to prevent malaria transmission.

Subunit vaccine

A vaccine based on a small portion of the organism, usually a peptide or protein.

Vaccine resistance

The ability of malaria parasites to escape strain-specific immune responses by exploiting genetic diversity to increase the frequencies of non-vaccine-type variants in a population or to evolve new diverse forms.

Whole-organism vaccine

A vaccine based on an attenuated or killed whole parasite.

Notes

Acknowledgments

The author is supported by the National Institute of Allergy and Infectious Diseases of the U.S. National Institutes of Health, by the Doris Duke Charitable Foundation, and by the Howard Hughes Medical Institute and wishes to thank Kirsten Lyke, Kavita Gandhi, Matthew Laurens, Mark Travassos, Thomas Richie, and Judith Epstein for critical reading of the manuscript and to acknowledge the U.S. Agency for International Development, the Walter Reed Army Institute of Research, GlaxoSmithKline Biologicals, Sanaria Inc., the U.S. Military Malaria Vaccine Program – Naval Medical Research Center, and the Malaria Research and Training Center of the University of Bamako, Mali, for collaboration on malaria vaccine trials.

Bibliography

Primary Literature

  1. 1.
    Garnham PCC (1966) Malaria parasites and other haemosporidia. Blackwell, OxfordGoogle Scholar
  2. 2.
    World Health Organization (2008) The global malaria action plan for a malaria free world. World Health Organization, GenevaGoogle Scholar
  3. 3.
    Rieckmann KH (2006) The chequered history of malaria control: are new and better tools the ultimate answer? Ann Trop Med Parasitol 100:647–662. doi:10.1179/136485906X112185PubMedCrossRefGoogle Scholar
  4. 4.
    WHO (2007) United Arab Emirates certified malaria-free. Wkly Epidemiol Rec 82:30–32Google Scholar
  5. 5.
    Roberts L, Enserink M (2007) Malaria. Did they really say…eradication? Science 318:1544–1545PubMedCrossRefGoogle Scholar
  6. 6.
    Plowe CV, Alonso P, Hoffman SL (2009) The potential role of vaccines in the elimination of falciparum malaria and the eventual eradication of malaria. J Infect Dis 200:1646–1649. doi:10.1086/646613 PubMedCrossRefGoogle Scholar
  7. 7.
    Henderson DA (1999) Lessons from the eradication campaigns. Vaccine 17(Suppl 3):S53–S55, S0264410X99002935 [pii]PubMedCrossRefGoogle Scholar
  8. 8.
    Casares S, Brumeanu TD, Richie TL (2010) The RTS,S malaria vaccine. Vaccine 28:4880–4894. doi:10.1016/j.vaccine.2010.05.033, S0264-410X(10)00721–8 [pii]PubMedCrossRefGoogle Scholar
  9. 9.
    Cox-Singh J, Davis TM, Lee KS, Shamsul SS, Matusop A, Ratnam S, Rahman HA, Conway DJ, Singh B (2008) Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clin Infect Dis 46:165–171. doi:10.1086/524888PubMedCrossRefGoogle Scholar
  10. 10.
    Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM (2007) Vivax malaria: neglected and not benign. Am J Trop Med Hyg 77:79–87, 77/6_Suppl/79 [pii]PubMedGoogle Scholar
  11. 11.
    The malERA Consultative Group on Vaccines (2010) A research agenda for malaria eradication: vaccines. PLoS Med 8:e1000398CrossRefGoogle Scholar
  12. 12.
    Baruch DI, Pasloske BL, Singh HB, Bi X, Ma XC, Feldman M, Taraschi TF, Howard RJ (1995) Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82:77–87PubMedCrossRefGoogle Scholar
  13. 13.
    Su X, Heatwole VM, Wertheimer SP, Guinet F, Herrfeldt JA, Peterson DS, Ravetch JV, Wellems TE (1995) The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82:89–100PubMedCrossRefGoogle Scholar
  14. 14.
    Smith JD, Chitnis CE, Craig AG, Roberts DJ, Hudson-Taylor DE, Peterson DS, Pinches R, Newbold CI, Miller LH (1995) Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82:101–110PubMedCrossRefGoogle Scholar
  15. 15.
    Miller LH, Baruch DI, Marsh K, Doumbo OK (2002) The pathogenic basis of malaria. Nature 415:673–679PubMedCrossRefGoogle Scholar
  16. 16.
    Nash GB, O’Brien E, Gordon-Smith EC, Dormandy JA (1989) Abnormalities in the mechanical properties of red blood cells caused by Plasmodium falciparum. Blood 74:855–861PubMedGoogle Scholar
  17. 17.
    Gupta S, Snow RW, Donnelly CA, Marsh K, Newbold C (1999) Immunity to non-cerebral severe malaria is acquired after one or two infections. Nat Med 5:340–343PubMedCrossRefGoogle Scholar
  18. 18.
    Hviid L (2005) Naturally acquired immunity to Plasmodium falciparum malaria in Africa. Acta Trop 95:270–275. doi:10.1016/j.actatropica.2005.06.012, S0001-706X(05)00165-8PubMedCrossRefGoogle Scholar
  19. 19.
    Baird JK, Jones TR, Danudirgo EW, Annis BA, Bangs MJ, Basri H, Purnomo MS (1991) Age-dependent acquired protection against Plasmodium falciparum in people having two years exposure to hyperendemic malaria. Am J Trop Med Hyg 45:65–76PubMedGoogle Scholar
  20. 20.
    Duffy PE (2007) Plasmodium in the placenta: parasites, parity, protection, prevention and possibly preeclampsia. Parasitology 134:1877–1881. doi:10.1017/S0031182007000170, S0031182007000170 [pii]PubMedCrossRefGoogle Scholar
  21. 21.
    Tanner M, de Savigny D (2008) Malaria eradication back on the table. Bull World Health Organ 86:82, S0042-96862008000200002 [pii]PubMedCrossRefGoogle Scholar
  22. 22.
    Cohen S, McGregor IA, Carrington S (1961) Gamma-globulin and acquired immunity to human malaria. Nature 192:733–737PubMedCrossRefGoogle Scholar
  23. 23.
    McGregor IA, Carrington S, Cohen S (1963) Treatment of East African P. falciparum malaria with West African human gamma-globulin. Trans R Soc Trop Med Hyg 50:170–175CrossRefGoogle Scholar
  24. 24.
    Collins WE, Jeffery GM (1999) A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum in patients previously infected with heterologous species of Plasmodium: effect on development of parasitologic and clinical immunity. Am J Trop Med Hyg 61:36–43PubMedGoogle Scholar
  25. 25.
    Collins WE, Jeffery GM (1999) A retrospective examination of secondary sporozoite- and trophozoite-induced infections with Plasmodium falciparum: development of parasitologic and clinical immunity following secondary infection. Am J Trop Med Hyg 61:20–35PubMedGoogle Scholar
  26. 26.
    Thomas AW, Trape JF, Rogier C, Goncalves A, Rosario VE, Narum DL (1994) High prevalence of natural antibodies against Plasmodium falciparum 83-kilodalton apical membrane antigen (PF83/AMA-1) as detected by capture-enzyme-linked immunosorbent assay using full-length baculovirus recombinant PF83/AMA-1. Am J Trop Med Hyg 51:730–740PubMedGoogle Scholar
  27. 27.
    Egan AF, Chappel JA, Burghaus PA, Morris JS, McBride JS, Holder AA, Kaslow DC, Riley EM (1995) Serum antibodies from malaria-exposed people recognize conserved epitopes formed by the two epidermal growth factor motifs of MSP1(19), the carboxy-terminal fragment of the major merozoite surface protein of Plasmodium falciparum. Infect Immun 63:456–466PubMedGoogle Scholar
  28. 28.
    Schofield L (1989) T cell immunity to malaria sporozoites. Exp Parasitol 68:357–364PubMedCrossRefGoogle Scholar
  29. 29.
    Doolan DL, Mu Y, Unal B, Sundaresh S, Hirst S, Valdez C, Randall A, Molina D, Liang X, Freilich DA, Oloo JA, Blair PL, Aguiar JC, Baldi P, Davies DH, Felgner PL (2008) Profiling humoral immune responses to P. falciparum infection with protein microarrays. Proteomics 8:4680–4694PubMedCrossRefGoogle Scholar
  30. 30.
    Crompton PD, Kayala MA, Traore B, Kayentao K, Ongoiba A, Weiss GE, Molina DM, Burk CR, Waisberg M, Jasinskas A, Tan X, Doumbo S, Doumtabe D, Kone Y, Narum DL, Liang X, Doumbo OK, Miller LH, Doolan DL, Baldi P, Felgner PL, Pierce SK (2010) A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proc Natl Acad Sci USA 107:6958–6963. doi:10.1073/pnas.1001323107, 1001323107 [pii]PubMedCrossRefGoogle Scholar
  31. 31.
    Allison AC (1954) Protection afforded by sickle-cell trait against subtertian malarial infection. Br Med J 1:290–294PubMedCrossRefGoogle Scholar
  32. 32.
    Kay AC, Kuhl W, Prchal J, Beutler E (1992) The origin of glucose-6-phosphate-dehydrogenase (G6PD) polymorphisms in African-Americans. Am J Hum Genet 50:394–398PubMedGoogle Scholar
  33. 33.
    Agarwal A, Guindo A, Cissoko Y, Taylor JG, Coulibaly D, Kone A, Kayentao K, Djimde A, Plowe CV, Doumbo O, Wellems TE, Diallo D (2000) Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S. Blood 96:2358–2363PubMedGoogle Scholar
  34. 34.
    Flint J, Hill AV, Bowden DK, Oppenheimer SJ, Sill PR, Serjeantson SW, Bana-Koiri J, Bhatia K, Alpers MP, Boyce AJ (1986) High frequencies of alpha-thalassaemia are the result of natural selection by malaria. Nature 321:744–750PubMedCrossRefGoogle Scholar
  35. 35.
    Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, Bennett S, Brewster D, McMichael AJ, Greenwood BM (1991) Common west African HLA antigens are associated with protection from severe malaria. Nature 352:595–600PubMedCrossRefGoogle Scholar
  36. 36.
    Miller LH, Mason SJ, Clyde DF, McGinniss MH (1976) The resistance factor to Plasmodium vivax in blacks. The Duffy- blood-group genotype, FyFy. N Engl J Med 295:302–304PubMedCrossRefGoogle Scholar
  37. 37.
    Bruce-Chwatt LJ (1981) Alphonse Laveran’s discovery 100 years ago and today’s global fight against malaria. J R Soc Med 74:531–8PubMedGoogle Scholar
  38. 38.
    Ross R (1897) Observations on a condition necessary to the transformation of the malaria crescent. Br Med J 1:251–255PubMedCrossRefGoogle Scholar
  39. 39.
    Russell PF, Mohan BN (1942) The immunization of fowls against mosquito-borne Plamodium gallinaceum by injections of serum and of inactivated homologous sporozoites. J Exp Med 76:477–495PubMedCrossRefGoogle Scholar
  40. 40.
    Freund J, Sommer HE, Walter AW (1945) Immunization against malaria: vaccination of ducks with killed parasites incorporated with adjuvants. Science 102:200–202PubMedCrossRefGoogle Scholar
  41. 41.
    Freund J, Thomson KJ, Sommer HE, Walter AW, Schenkein EL (1945) Immunization of rhesus monkeys against malarial infection (P. knowlesi) with killed parasites and adjuvants. Science 102:202–204. doi:10.1126/science.102.2643.202, 102/2643/202 [pii]PubMedCrossRefGoogle Scholar
  42. 42.
    Jacobs HR (1943) Immunization against malaria. Increased protection by vaccination of ducklings with saline-insoluble residues of Plasmodium lophurae mixed with a bacterial toxin. Am J Trop Med Hyg s1-23:597–606Google Scholar
  43. 43.
    Redmond WB (1939) Immunization of birds to malaria by vaccination. J Parasitol 25:28–29Google Scholar
  44. 44.
    Bennison BE, Coatney GR (1949) Effects of X-irradiation on Plasmodium gallinaceum and Plasmodium lophurae infections in young chicks. J Natl Malar Soc 8:280–289PubMedGoogle Scholar
  45. 45.
    Ceithaml J, Evans EA Jr (1946) The biochemistry of the malaria parasite; the in vitro effects of x-rays upon Plasmodium gallinaceum. J Infect Dis 78:190–197PubMedCrossRefGoogle Scholar
  46. 46.
    Nussenzweig RS, Vanderberg J, Most H, Orton C (1967) Protective immunity produced by the injection of x-irradiated sporozoites of Plasmodium berghei. Nature 216:160–162PubMedCrossRefGoogle Scholar
  47. 47.
    Hoffman SL, Billingsley PF, James E, Richman A, Loyevsky M, Li T, Chakravarty S, Gunasekera A, Li M, Stafford R, Ahumada A, Epstein JE, Sedegah M, Reyes S, Richie TL, Lyke KE, Edelman R, Laurens M, Plowe CV, Sim BK (2010) Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria. Hum Vaccin 6:97–106, 10396 [pii]PubMedCrossRefGoogle Scholar
  48. 48.
    Heidelberger M, Prout C, Hindle JA, Rose AS (1946) Studies in human malaria III. An attempt at vaccination of paretics against blood-borne infection with P vivax. J Immunol 53:109–112PubMedGoogle Scholar
  49. 49.
    Clyde DF, Most H, McCarthy VC, Vanderberg JP (1973) Immunization of man against sporozoite-induced falciparum malaria. Am J Med Sci 266:169–177PubMedCrossRefGoogle Scholar
  50. 50.
    Rieckmann KH, Carson PE, Beaudoin RL, Cassells JS, Sell KW (1974) Letter: sporozoite induced immunity in man against an Ethiopian strain of Plasmodium falciparum. Trans R Soc Trop Med Hyg 68:258–259PubMedCrossRefGoogle Scholar
  51. 51.
    Luke TC, Hoffman SL (2003) Rationale and plans for developing a non-replicating, metabolically active, radiation-attenuated Plasmodium falciparum sporozoite vaccine. J Exp Biol 206:3803–3808PubMedCrossRefGoogle Scholar
  52. 52.
    Vanderberg JP (2009) Reflections on early malaria vaccine studies, the first successful human malaria vaccination, and beyond. Vaccine 27:2–9. doi:10.1016/j.vaccine.2008.10.028, S0264-410X(08)01414-X [pii]PubMedCrossRefGoogle Scholar
  53. 53.
    Trager W, Jensen JB (1976) Human malaria parasites in continuous culture. Science 193:673–675PubMedCrossRefGoogle Scholar
  54. 54.
    Haynes JD, Diggs CL, Hines FA, Desjardins RE (1976) Culture of human malaria parasites Plasmodium falciparum. Nature 263:767–769PubMedCrossRefGoogle Scholar
  55. 55.
    World Health Organization (2010) Initiative for vaccine research: malaria vaccines. WHO, GenevaGoogle Scholar
  56. 56.
    Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S, Paulsen IT, James K, Eisen JA, Rutherford K, Salzberg SL, Craig A, Kyes S, Chan MS, Nene V, Shallom SJ, Suh B, Peterson J, Angiuoli S, Pertea M, Allen J, Selengut J, Haft D, Mather MW, Vaidya AB, Martin DM, Fairlamb AH, Fraunholz MJ, Roos DS, Ralph SA, McFadden GI, Cummings LM, Subramanian GM, Mungall C, Venter JC, Carucci DJ, Hoffman SL, Newbold C, Davis RW, Fraser CM, Barrell B (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419:498–511PubMedCrossRefGoogle Scholar
  57. 57.
    Takala SL, Plowe CV (2009) Genetic diversity and malaria vaccine design, testing and efficacy: preventing and overcoming ‘vaccine resistant malaria’. Parasite Immunol 31:560–573. doi:10.1111/j.1365–3024.2009.01138.x, PIM1138 [pii]PubMedCrossRefGoogle Scholar
  58. 58.
    Takala SL, Coulibaly D, Thera MA, Dicko A, Smith DL, Guindo AB, Kone AK, Traore K, Ouattara A, Djimde AA, Sehdev PS, Lyke KE, Diallo DA, Doumbo OK, Plowe CV (2007) Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali. PLoS Med 4:e93PubMedCrossRefGoogle Scholar
  59. 59.
    Takala SL, Coulibaly D, Thera MA, Batchelor AH, Cummings MP, Escalante AA, Ouattara A, Traore K, Niangaly A, Djimde AA, Doumbo OK, Plowe CV (2009) Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development. Sci Transl Med 1:2ra5PubMedCrossRefGoogle Scholar
  60. 60.
    Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Milman J, Mandomando I, Spiessens B, Guinovart C, Espasa M, Bassat Q, Aide P, Ofori-Anyinam O, Navia MM, Corachan S, Ceuppens M, Dubois MC, Demoitie MA, Dubovsky F, Menendez C, Tornieporth N, Ballou WR, Thompson R, Cohen J (2004) Efficacy of the RTS, S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet 364:1411–1420PubMedCrossRefGoogle Scholar
  61. 61.
    Egan AF, Blackman MJ, Kaslow DC (2000) Vaccine efficacy of recombinant Plasmodium falciparum merozoite surface protein 1 in malaria-naive, -exposed, and/or -rechallenged Aotus vociferans monkeys. Infect Immun 68:1418–1427PubMedCrossRefGoogle Scholar
  62. 62.
    Thera MA, Doumbo OK, Coulibaly D, Diallo DA, Sagara I, Dicko A, Diemert DJ, Heppner DG Jr, Stewart VA, Angov E, Soisson L, Leach A, Tucker K, Lyke KE, Plowe CV (2006) Safety and allele-specific immunogenicity of a malaria vaccine in Malian adults: results of a phase I randomized trial. PLoS Clin Trials 1:e34. doi:10.1371/journal.pctr.0010034PubMedCrossRefGoogle Scholar
  63. 63.
    Stoute JA, Gombe J, Withers MR, Siangla J, McKinney D, Onyango M, Cummings JF, Milman J, Tucker K, Soisson L, Stewart VA, Lyon JA, Angov E, Leach A, Cohen J, Kester KE, Ockenhouse CF, Holland CA, Diggs CL, Wittes J, Heppner DG Jr (2007) Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya. Vaccine 25:176–184PubMedCrossRefGoogle Scholar
  64. 64.
    Withers MR, McKinney D, Ogutu BR, Waitumbi JN, Milman JB, Apollo OJ, Allen OG, Tucker K, Soisson LA, Diggs C, Leach A, Wittes J, Dubovsky F, Stewart VA, Remich SA, Cohen J, Ballou WR, Holland CA, Lyon JA, Angov E, Stoute JA, Martin SK, Heppner DG (2006) Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized Phase Ib dose-escalation trial in Kenyan children. PLoS Clin Trials 1:e32PubMedCrossRefGoogle Scholar
  65. 65.
    Ogutu BR, Apollo OJ, McKinney D, Okoth W, Siangla J, Dubovsky F, Tucker K, Waitumbi JN, Diggs C, Wittes J, Malkin E, Leach A, Soisson LA, Milman JB, Otieno L, Holland CA, Polhemus M, Remich SA, Ockenhouse CF, Cohen J, Ballou WR, Martin SK, Angov E, Stewart VA, Lyon JA, Heppner DG, Withers MR (2009) Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS One 4:e4708PubMedCrossRefGoogle Scholar
  66. 66.
    Sagara I, Dicko A, Ellis RD, Fay MP, Diawara SI, Assadou MH, Sissoko MS, Kone M, Diallo AI, Saye R, Guindo MA, Kante O, Niambele MB, Miura K, Mullen GE, Pierce M, Martin LB, Dolo A, Diallo DA, Doumbo OK, Miller LH, Saul A (2009) A randomized controlled phase 2 trial of the blood stage AMA1-C1/Alhydrogel malaria vaccine in children in Mali. Vaccine 27:3090–3098PubMedCrossRefGoogle Scholar
  67. 67.
    Thera MA, Doumbo OK, Coulibaly D, Diallo DA, Kone AK, Guindo AB, Traore K, Dicko A, Sagara I, Sissoko MS, Baby M, Sissoko M, Diarra I, Niangaly A, Dolo A, Daou M, Diawara SI, Heppner DG, Stewart VA, Angov E, Bergmann-Leitner ES, Lanar DE, Dutta S, Soisson L, Diggs CL, Leach A, Owusu A, Dubois MC, Cohen J, Nixon JN, Gregson A, Takala SL, Lyke KE, Plowe CV (2008) Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a Phase 1 randomized controlled trial. PLoS One 3:e1465PubMedCrossRefGoogle Scholar
  68. 68.
    Thera MA, Doumbo OK, Coulibaly D, Laurens MB, Kone AK, Guindo AB, Traore K, Sissoko M, Diallo DA, Diarra I, Kouriba B, Daou M, Dolo A, Baby M, Sissoko MS, Sagara I, Niangaly A, Traore I, Olotu A, Godeaux O, Leach A, Dubois MC, Ballou WR, Cohen J, Thompson D, Dube T, Soisson L, Diggs CL, Takala SL, Lyke KE, House B, Lanar DE, Dutta S, Heppner DG, Plowe CV (2010) Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial. PLoS One 5:e9041. doi:10.1371/journal.pone.0009041 PubMedCrossRefGoogle Scholar
  69. 69.
    Dame JB, Williams JL, McCutchan TF, Weber JL, Wirtz RA, Hockmeyer WT, Maloy WL, Haynes JD, Schneider RD (1984) Structure of the gene encoding the immunodominant surface antigen on the sporozoite of the human malaria parasite Plasmodium falciparum. Science 225:593–599PubMedCrossRefGoogle Scholar
  70. 70.
    Beier JC, Vanderburg JP (1998) Sporogonic development in the mosquito. In: Sherman IW (ed) Malaria parasite biology, pathogenesis, and protection. ASM Press, Washington, DCGoogle Scholar
  71. 71.
    Ballou WR, Rothbard J, Wirtz RA, Gordon DM, Williams JS, Gore RW, Schneider I, Hollingdale MR, Beaudoin RL, Maloy WL et al (1985) Immunogenicity of synthetic peptides from circumsporozoite protein of Plasmodium falciparum. Science 228:996–999PubMedCrossRefGoogle Scholar
  72. 72.
    Hollingdale MR, Nardin EH, Tharavanij S, Schwartz AL, Nussenzweig RS (1984) Inhibition of entry of Plasmodium falciparum and P. vivax sporozoites into cultured cells; an in vitro assay of protective antibodies. J Immunol 132:909–913PubMedGoogle Scholar
  73. 73.
    Herrington DA, Clyde DF, Losonsky G, Cortesia M, Murphy JR, Davis J, Baqar S, Felix AM, Heimer EP, Gillessen D et al (1987) Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites. Nature 328:257–259PubMedCrossRefGoogle Scholar
  74. 74.
    Ballou WR, Hoffman SL, Sherwood JA, Hollingdale MR, Neva FA, Hockmeyer WT, Gordon DM, Schneider I, Wirtz RA, Young JF (1987) Safety and efficacy of a recombinant DNA Plasmodium falciparum sporozoite vaccine. Lancet 1:1277–1281PubMedCrossRefGoogle Scholar
  75. 75.
    Hoffman SL, Oster CN, Plowe CV, Woollett GR, Beier JC, Chulay JD, Wirtz RA, Hollingdale MR, Mugambi M (1987) Naturally acquired antibodies to sporozoites do not prevent malaria: vaccine development implications. Science 237:639–642PubMedCrossRefGoogle Scholar
  76. 76.
    Sherwood JA, Copeland RS, Taylor KA, Abok K, Oloo AJ, Were JB, Strickland GT, Gordon DM, Ballou WR, Bales JDJ, Wirtz RA, Wittes J, Gross M, Que JU, Cryz SJ, Oster CN, Roberts CR, Sadoff JC (1996) Plasmodium falciparum circumsporozoite vaccine immunogenicity and efficacy trial with natural challenge quantitation in an area of endemic human malaria of Kenya. Vaccine 14:817–827PubMedCrossRefGoogle Scholar
  77. 77.
    Gordon DM, McGovern TW, Krzych U, Cohen JC, Schneider I, LaChance R, Heppner DG, Yuan G, Hollingdale M, Slaoui M (1995) Safety, immunogenicity, and efficacy of a recombinantly produced Plasmodium falciparum circumsporozoite protein-hepatitis B surface antigen subunit vaccine. J Infect Dis 171:1576–1585PubMedCrossRefGoogle Scholar
  78. 78.
    Stoute JA, Slaoui M, Heppner DG, Momin P, Kester KE, Desmons P, Wellde BT, Garcon N, Krzych U, Marchand M (1997) A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS, S malaria vaccine evaluation group. N Engl J Med 336:86–91. doi:10.1056/NEJM199701093360202PubMedCrossRefGoogle Scholar
  79. 79.
    Kester KE, McKinney DA, Tornieporth N, Ockenhouse CF, Heppner DG, Hall T, Krzych U, Delchambre M, Voss G, Dowler MG, Palensky J, Wittes J, Cohen J, Ballou WR (2001) Efficacy of recombinant circumsporozoite protein vaccine regimens against experimental Plasmodium falciparum malaria. J Infect Dis 183:640–647PubMedCrossRefGoogle Scholar
  80. 80.
    Bojang KA, Milligan PJ, Pinder M, Vigneron L, Alloueche A, Kester KE, Ballou WR, Conway DJ, Reece WH, Gothard P, Yamuah L, Delchambre M, Voss G, Greenwood BM, Hill A, McAdam KP, Tornieporth N, Cohen JD, Doherty T (2001) Efficacy of RTS, S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial. Lancet 358:1927–1934PubMedCrossRefGoogle Scholar
  81. 81.
    Bejon P, Lusingu J, Olotu A, Leach A, Lievens M, Vekemans J, Mshamu S, Lang T, Gould J, Dubois MC, Demoitie MA, Stallaert JF, Vansadia P, Carter T, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Ballou WR, Cohen J, Riley EM, Lemnge MM, Marsh K, von Seidlein L (2008) Efficacy of RTS, S/AS01E vaccine against malaria in children 5 to 17 months of age. N Engl J Med 359:2521–2532. doi:10.1056/NEJMoa0807381, NEJMoa0807381 [pii]PubMedCrossRefGoogle Scholar
  82. 82.
    Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Aide P, Sigauque B, Milman J, Mandomando I, Bassat Q, Guinovart C, Espasa M, Corachan S, Lievens M, Navia MM, Dubois MC, Menendez C, Dubovsky F, Cohen J, Thompson R, Ballou WR (2005) Duration of protection with RTS, S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled trial. Lancet 366:2012–2018PubMedCrossRefGoogle Scholar
  83. 83.
    Sacarlal J, Aide P, Aponte JJ, Renom M, Leach A, Mandomando I, Lievens M, Bassat Q, Lafuente S, Macete E, Vekemans J, Guinovart C, Sigauque B, Sillman M, Milman J, Dubois MC, Demoitie MA, Thonnard J, Menendez C, Ballou WR, Cohen J, Alonso PL (2009) Long-term safety and efficacy of the RTS, S/AS02A malaria vaccine in Mozambican children. J Infect Dis 200:329–336. doi:10.1086/600119PubMedCrossRefGoogle Scholar
  84. 84.
    Heppner DG Jr, Kester KE, Ockenhouse CF, Tornieporth N, Ofori O, Lyon JA, Stewart VA, Dubois P, Lanar DE, Krzych U, Moris P, Angov E, Cummings JF, Leach A, Hall BT, Dutta S, Schwenk R, Hillier C, Barbosa A, Ware LA, Nair L, Darko CA, Withers MR, Ogutu B, Polhemus ME, Fukuda M, Pichyangkul S, Gettyacamin M, Diggs C, Soisson L, Milman J, Dubois MC, Garcon N, Tucker K, Wittes J, Plowe CV, Thera MA, Duombo OK, Pau MG, Goudsmit J, Ballou WR, Cohen J (2005) Towards an RTS, S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research. Vaccine 23:2243–2250PubMedCrossRefGoogle Scholar
  85. 85.
    Stewart VA, McGrath SM, Dubois PM, Pau MG, Mettens P, Shott J, Cobb M, Burge JR, Larson D, Ware LA, Demoitie MA, Weverling GJ, Bayat B, Custers JH, Dubois MC, Cohen J, Goudsmit J, Heppner DG Jr (2007) Priming with an adenovirus 35-circumsporozoite protein (CS) vaccine followed by RTS, S/AS01B boosting significantly improves immunogenicity to Plasmodium falciparum CS compared to that with either malaria vaccine alone. Infect Immun 75:2283–2290PubMedCrossRefGoogle Scholar
  86. 86.
    Cummings JF, Spring MD, Schwenk RJ, Ockenhouse CF, Kester KE, Polhemus ME, Walsh DS, Yoon IK, Prosperi C, Juompan LY, Lanar DE, Krzych U, Hall BT, Ware LA, Stewart VA, Williams J, Dowler M, Nielsen RK, Hillier CJ, Giersing BK, Dubovsky F, Malkin E, Tucker K, Dubois MC, Cohen JD, Ballou WR, Heppner DG Jr (2010) Recombinant liver stage antigen-1 (LSA-1) formulated with AS01 or AS02 is safe, elicits high titer antibody and induces IFN-gamma/IL-2 CD4+ T cells but does not protect against experimental Plasmodium falciparum infection. Vaccine 28:5135–5144. doi:10.1016/j.vaccine.2009.08.046, S0264-410X(09)01231-6 [pii]PubMedCrossRefGoogle Scholar
  87. 87.
    Hill AV, Reyes-Sandoval A, O’Hara G, Ewer K, Lawrie A, Goodman A, Nicosia A, Folgori A, Colloca S, Cortese R, Gilbert SC, Draper SJ (2010) Prime-boost vectored malaria vaccines: progress and prospects. Hum Vaccin 6:78–83, 10116 [pii]PubMedCrossRefGoogle Scholar
  88. 88.
    Kaba SA, Brando C, Guo Q, Mittelholzer C, Raman S, Tropel D, Aebi U, Burkhard P, Lanar DE (2009) A nonadjuvanted polypeptide nanoparticle vaccine confers long-lasting protection against rodent malaria. J Immunol 183:7268–7277. doi:10.4049/jimmunol.0901957, jimmunol.0901957 [pii]PubMedCrossRefGoogle Scholar
  89. 89.
    Bergmann-Leitner ES, Mease RM, de la Vega P, Savranskaya T, Polhemus M, Ockenhouse C, Angov E (2010) Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei. PLoS One 5:e12294. doi:10.1371/journal.pone.0012294PubMedCrossRefGoogle Scholar
  90. 90.
    Blackman MJ, Heidrich HG, Donachie S, McBride JS, Holder AA (1990) A single fragment of a malaria merozoite surface protein remains on the parasite during red cell invasion and is the target of invasion-inhibiting antibodies. J Exp Med 172:379–382PubMedCrossRefGoogle Scholar
  91. 91.
    Egan AF, Morris J, Barnish G, Allen S, Greenwood BM, Kaslow DC, Holder AA, Riley EM (1996) Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1. J Infect Dis 173:765–9PubMedCrossRefGoogle Scholar
  92. 92.
    Riley EM, Allen SJ, Wheeler JG, Blackman MJ, Bennett S, Takacs B, Schonfeld HJ, Holder AA, Greenwood BM (1992) Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (PfMSP1) of Plasmodium falciparum are associated with reduced malaria morbidity. Parasite Immunol 14:321–37PubMedCrossRefGoogle Scholar
  93. 93.
    Stowers AW, Cioce V, Shimp RL, Lawson M, Hui G, Muratova O, Kaslow DC, Robinson R, Long CA, Miller LH (2001) Efficacy of two alternate vaccines based on Plasmodium falciparum merozoite surface protein 1 in an Aotus challenge trial. Infect Immun 69:18–1546. doi:10.1128/IAI.69.3.18-1546.2001CrossRefGoogle Scholar
  94. 94.
    Peterson MG, Marshall VM, Smythe JA, Crewther PE, Lew A, Silva A, Anders RF, Kemp DJ (1989) Integral membrane protein located in the apical complex of Plasmodium falciparum. Mol Cell Biol 9:3151–3154PubMedGoogle Scholar
  95. 95.
    Narum DL, Thomas AW (1994) Differential localization of full-length and processed forms of PF83/AMA-1 an apical membrane antigen of Plasmodium falciparum merozoites. Mol Biochem Parasitol 67:59–68PubMedCrossRefGoogle Scholar
  96. 96.
    Mitchell GH, Thomas AW, Margos G, Dluzewski AR, Bannister LH (2004) Apical membrane antigen 1, a major malaria vaccine candidate, mediates the close attachment of invasive merozoites to host red blood cells. Infect Immun 72:154–158PubMedCrossRefGoogle Scholar
  97. 97.
    Florens L, Washburn MP, Raine JD, Anthony RM, Grainger M, Haynes JD, Moch JK, Muster N, Sacci JB, Tabb DL, Witney AA, Wolters D, Wu Y, Gardner MJ, Holder AA, Sinden RE, Yates JR, Carucci DJ (2002) A proteomic view of the Plasmodium falciparum life cycle. Nature 419:520–526PubMedCrossRefGoogle Scholar
  98. 98.
    Hodder AN, Crewther PE, Anders RF (2001) Specificity of the protective antibody response to apical membrane antigen 1. Infect Immun 69:3286–94PubMedCrossRefGoogle Scholar
  99. 99.
    Polley SD, Mwangi T, Kocken CH, Thomas AW, Dutta S, Lanar DE, Remarque E, Ross A, Williams TN, Mwambingu G, Lowe B, Conway DJ, Marsh K (2004) Human antibodies to recombinant protein constructs of Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) and their associations with protection from malaria. Vaccine 23:718–728PubMedCrossRefGoogle Scholar
  100. 100.
    Dutta S, Lee SY, Batchelor AH, Lanar DE (2007) Structural basis of antigenic escape of a malaria vaccine candidate. Proc Natl Acad Sci USA 104:12488–12493PubMedCrossRefGoogle Scholar
  101. 101.
    Healer J, Murphy V, Hodder AN, Masciantonio R, Gemmill AW, Anders RF, Cowman AF, Batchelor A (2004) Allelic polymorphisms in apical membrane antigen-1 are responsible for evasion of antibody-mediated inhibition in Plasmodium falciparum. Mol Microbiol 52:159–168PubMedCrossRefGoogle Scholar
  102. 102.
    Ouattara A, Mu J, Takala-Harrison S, Saye R, Sagara I, Dicko A, Niangaly A, Duan J, Ellis RD, Miller LH, Su XZ, Plowe CV, Doumbo OK (2010) Lack of allele-specific efficacy of a bivalent AMA1 malaria vaccine. Malar J 9:175. doi:10.1186/1475-2875-9-175, 1475-2875-9-175 [pii]PubMedCrossRefGoogle Scholar
  103. 103.
    Spring MD, Cummings JF, Ockenhouse CF, Dutta S, Reidler R, Angov E, Bergmann-Leitner E, Stewart VA, Bittner S, Juompan L, Kortepeter MG, Nielsen R, Krzych U, Tierney E, Ware LA, Dowler M, Hermsen CC, Sauerwein RW, de Vlas SJ, Ofori-Anyinam O, Lanar DE, Williams JL, Kester KE, Tucker K, Shi M, Malkin E, Long C, Diggs CL, Soisson L, Dubois MC, Ballou WR, Cohen J, Heppner DG Jr (2009) Phase 1/2a study of the malaria vaccine candidate apical membrane antigen-1 (AMA-1) administered in adjuvant system AS01B or AS02A. PLoS One 4:e5254PubMedCrossRefGoogle Scholar
  104. 104.
    Thera MA, Doumbo OK, Coulibaly D, Laurens MB, Ouattara A, Kone AK, Guindo AB, Traore K, Traore I, Kouriba B, Diallo DA, Diarra I, Daou M, Dolo A, Tolo Y, Sissoko MS, Niangaly A, Sissoko M, Takala-Harrison S, Lyke KE, Wu Y, Blackwelder WC, Godeaux O, Vekemans J, Dubois M-C, Ballou WR, Cohen J, Thompson D, Dube T, Soisson L, Diggs CL, House B, Lanar DE, Dutta S, Heppner DG Jr., Plowe CV (2011) A field trial to assess a blood-stage malaria vaccine. N Engl J Med 365:1004–13PubMedCrossRefGoogle Scholar
  105. 105.
    Remarque EJ, Faber BW, Kocken CH, Thomas AW (2008) A diversity-covering approach to immunization with Plasmodium falciparum apical membrane antigen 1 induces broader allelic recognition and growth inhibition responses in rabbits. Infect Immun 76:2660–2670. doi:10.1128/IAI.00170-08, IAI.00170-08 [pii]PubMedCrossRefGoogle Scholar
  106. 106.
    Remarque EJ, Faber BW, Kocken CH, Thomas AW (2008) Apical membrane antigen 1: a malaria vaccine candidate in review. Trends Parasitol 24:74–84. doi:10.1016/j.pt.2007.12.002, S1471-4922(07)00328-5 [pii]PubMedCrossRefGoogle Scholar
  107. 107.
    Dutta S, Dlugosz LS, Clayton JW, Pool CD, Haynes JD, Gasser RA III, Batchelor AH (2010) Alanine mutagenesis of the primary antigenic escape residue cluster, c1, of apical membrane antigen 1. Infect Immun 78:661–671. doi:10.1128/IAI.00866-09, IAI.00866-09 [pii]PubMedCrossRefGoogle Scholar
  108. 108.
    Klein MM, Gittis AG, Su HP, Makobongo MO, Moore JM, Singh S, Miller LH, Garboczi DN (2008) The cysteine-rich interdomain region from the highly variable Plasmodium falciparum erythrocyte membrane protein-1 exhibits a conserved structure. PLoS Pathog 4:e1000147. doi:10.1371/journal.ppat.1000147PubMedCrossRefGoogle Scholar
  109. 109.
    Avril M, Cartwright MM, Hathaway MJ, Hommel M, Elliott SR, Williamson K, Narum DL, Duffy PE, Fried M, Beeson JG, Smith JD (2010) Immunization with VAR2CSA-DBL5 recombinant protein elicits broadly cross-reactive antibodies to placental Plasmodium falciparum-infected erythrocytes. Infect Immun 78:2248–2256. doi:10.1128/IAI.00410-09, IAI.00410-09 [pii]PubMedCrossRefGoogle Scholar
  110. 110.
    Barr PJ, Green KM, Gibson HL, Bathurst IC, Quakyi IA, Kaslow DC (1991) Recombinant Pfs25 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in experimental animals. J Exp Med 174:1203–1208PubMedCrossRefGoogle Scholar
  111. 111.
    Wu Y, Ellis RD, Shaffer D, Fontes E, Malkin EM, Mahanty S, Fay MP, Narum D, Rausch K, Miles AP, Aebig J, Orcutt A, Muratova O, Song G, Lambert L, Zhu D, Miura K, Long C, Saul A, Miller LH, Durbin AP (2008) Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51. PLoS One 3:e2636. doi:10.1371/journal.pone.0002636PubMedCrossRefGoogle Scholar
  112. 112.
    Dinglasan RR, Valenzuela JG, Azad AF (2005) Sugar epitopes as potential universal disease transmission blocking targets. Insect Biochem Mol Biol 35:1–10. doi:10.1016/j.ibmb.2004.09.005, S0965-1748(04)00159-6 [pii]PubMedCrossRefGoogle Scholar
  113. 113.
    Valero MV, Amador LR, Galindo C, Figueroa J, Bello MS, Murillo LA, Mora AL, Patarroyo G, Rocha CL, Rojas M (1993) Vaccination with SPf66, a chemically synthesised vaccine, against Plasmodium falciparum malaria in Colombia. Lancet 341:705–710PubMedCrossRefGoogle Scholar
  114. 114.
    Nosten F, Luxemburger C, Kyle DE, Ballou WR, Wittes J, Wah E, Chongsuphajaisiddhi T, Gordon DM, White NJ, Sadoff JC, Heppner DG (1996) Randomised double-blind placebo-controlled trial of SPf66 malaria vaccine in children in northwestern Thailand. Shoklo SPf66 Malaria Vaccine Trial Group. Lancet 348:701–707PubMedCrossRefGoogle Scholar
  115. 115.
    D’Alessandro U, Leach A, Drakeley CJ, Bennett S, Olaleye BO, Fegan GW, Jawara M, Langerock P, George MO, Targett GA (1995) Efficacy trial of malaria vaccine SPf66 in Gambian infants. Lancet 346:462–467PubMedCrossRefGoogle Scholar
  116. 116.
    Alonso PL, Smith T, Schellenberg JR, Masanja H, Mwankusye S, Urassa H, Bastos de Azevedo I, Chongela J, Kobero S, Menendez C et al (1994) Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania. Lancet 344:1175–1181PubMedCrossRefGoogle Scholar
  117. 117.
    Ockenhouse CF, Sun PF, Lanar DE, Wellde BT, Hall BT, Kester K, Stoute JA, Magill A, Krzych U, Farley L, Wirtz RA, Sadoff JC, Kaslow DC, Kumar S, Church LW, Crutcher JM, Wizel B, Hoffman S, Lalvani A, Hill AV, Tine JA, Guito KP, de Taisne C, Anders R, Ballou WR (1998) Phase I/IIa safety, immunogenicity, and efficacy trial of NYVAC-Pf7, a pox-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria. J Infect Dis 177:1664–1673PubMedCrossRefGoogle Scholar
  118. 118.
    Kumar S, Epstein JE, Richie TL, Nkrumah FK, Soisson L, Carucci DJ, Hoffman SL (2002) A multilateral effort to develop DNA vaccines against falciparum malaria. Trends Parasitol 18:129–135, S1471492201022073 [pii]PubMedCrossRefGoogle Scholar
  119. 119.
    Epstein JE, Tewari K, Lyke KE, Sim BK, Billingsley PF, Laurens MB, Gunasekera A, Chakravarty S, James ER, Sedegah M, Richman A, Velmurugan S, Reyes S, Li M, Tucker K, Ahumada A, Ruben AJ, Li T, Stafford R, Eappen AG, Tamminga C, Bennett JW, Ockenhouse CF, Murphy JR, Komisar J, Thomas N, Loyevsky M, Birkett A, Plowe CV, Loucq C, Edelman R, Richie TL, Seder RA, Hoffman SL (2011) Live attenuated malaria vaccine designed to protect through hepatic CD8+ T cell immunity. Science [Epub ahead of print]Google Scholar
  120. 120.
    VanBuskirk KM, O’Neill MT, de la Vega P, Maier AG, Krzych U, Williams J, Dowler MG, Sacci JB Jr, Kangwanrangsan N, Tsuboi T, Kneteman NM, Heppner DG Jr, Murdock BA, Mikolajczak SA, Aly AS, Cowman AF, Kappe SH (2009) Preerythrocytic, live-attenuated Plasmodium falciparum vaccine candidates by design. Proc Natl Acad Sci USA 106. doi:10.1073/pnas.0906387106, 13004–13009. 0906387106 [pii]Google Scholar
  121. 121.
    Pinzon-Charry A, McPhun V, Kienzle V, Hirunpetcharat C, Engwerda C, McCarthy J, Good MF (2010) Low doses of killed parasite in CpG elicit vigorous CD4+ T cell responses against blood-stage malaria in mice. J Clin Invest 120:2967–2978. doi:10.1172/JCI39222, 39222 [pii]PubMedCrossRefGoogle Scholar
  122. 122.
    McCarthy JS, Good MF (2010) Whole parasite blood stage malaria vaccines: a convergence of evidence. Hum Vaccin 6:114–123, 10394 [pii]PubMedCrossRefGoogle Scholar

Books and Reviews

  1. Bruder JT, Angov E, Limbach KJ, Richie TL (2010) Molecular vaccines for malaria. Hum Vaccin 6:54–77PubMedCrossRefGoogle Scholar
  2. Desowitz RS (1991) The malaria capers: more tales of parasites and people, research and reality. Norton, New YorkGoogle Scholar
  3. Dinglasan RR, Jacobs-Lorena M (2008) Flipping the paradigm on malaria transmission-blocking vaccines. Trends Parasitol 24:364–370PubMedCrossRefGoogle Scholar
  4. Hill AV, Reyes-Sandoval A, O’Hara G, Ewer K, Lawrie A, Goodman A, Nicosia A, Folgori A, Colloca S, Cortese R, Gilbert SC, Draper SJ (2010) Prime-boost vectored malaria vaccines: progress and prospects. Hum Vaccin 6:78–83PubMedCrossRefGoogle Scholar
  5. Hviid L (2010) The role of Plasmodium falciparum variant surface antigens in protective immunity and vaccine development. Hum Vaccin 6:84–89PubMedCrossRefGoogle Scholar
  6. Langhorne J, Ndungu FM, Sponaas AM, Marsh K (2008) Immunity to malaria: more questions than answers. Nat Immunol 9:725–732PubMedCrossRefGoogle Scholar
  7. Moorthy VS, Kieny MP (2010) Reducing empiricism in malaria vaccine design. Lancet Infect Dis 10:204–211PubMedCrossRefGoogle Scholar
  8. Richards JS, Beeson JG (2009) The future for blood-stage vaccines against malaria. Immunol Cell Biol 87:377–390PubMedCrossRefGoogle Scholar
  9. Shah S (2010) The fever: how malaria has ruled humankind for 500,000 years. Farrar, Straus and Giroux, New YorkGoogle Scholar
  10. Sherwin IW (2009) The elusive malaria vaccine: miracle or mirage? ASM Press, Washington, DCGoogle Scholar
  11. Vaughan AM, Wang R, Kappe SH (2010) Genetically engineered, attenuated whole-cell vaccine approaches for malaria. Hum Vaccin 6:107–113PubMedCrossRefGoogle Scholar
  12. Wykes M, Good MF (2007) A case for whole-parasite malaria vaccines. Int J Parasitol 37:705–712PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Howard Hughes Medical Institute/Center for Vaccine DevelopmentUniversity of Maryland School of MedicineBaltimoreUSA

Personalised recommendations