Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-26T20:59:41.213Z Has data issue: false hasContentIssue false

Advances and challenges in malaria vaccine development

Published online by Cambridge University Press:  16 December 2009

Ruobing Wang
Affiliation:
Seattle Biomedical Research Institute and Department of Global Health, University of Washington, Seattle, Washington, USA.
Joseph D. Smith
Affiliation:
Seattle Biomedical Research Institute and Department of Global Health, University of Washington, Seattle, Washington, USA.
Stefan H.I. Kappe*
Affiliation:
Seattle Biomedical Research Institute and Department of Global Health, University of Washington, Seattle, Washington, USA.
*
*Corresponding author: Stefan Kappe, Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109-5219, USA. Tel: +1 206 256 7205; Fax: +1 206 256 7229; E-mail: [email protected]

Abstract

Malaria remains one of the most devastating infectious diseases that threaten humankind. Human malaria is caused by five different species of Plasmodium parasites, each transmitted by the bite of female Anopheles mosquitoes. Plasmodia are eukaryotic protozoans with more than 5000 genes and a complex life cycle that takes place in the mosquito vector and the human host. The life cycle can be divided into pre-erythrocytic stages, erythrocytic stages and mosquito stages. Malaria vaccine research and development faces formidable obstacles because many vaccine candidates will probably only be effective in a specific species at a specific stage. In addition, Plasmodium actively subverts and escapes immune responses, possibly foiling vaccine-induced immunity. Although early successful vaccinations with irradiated, live-attenuated malaria parasites suggested that a vaccine is possible, until recently, most efforts have focused on subunit vaccine approaches. Blood-stage vaccines remain a primary research focus, but real progress is evident in the development of a partially efficacious recombinant pre-erythrocytic subunit vaccine and a live-attenuated sporozoite vaccine. It is unlikely that partially effective vaccines will eliminate malaria; however, they might prove useful in combination with existing control strategies. Elimination of malaria will probably ultimately depend on the development of highly effective vaccines.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Guerra, C.A. et al. (2008) The limits and intensity of Plasmodium falciparum transmission: implications for malaria control and elimination worldwide. PLoS Medicine 5, e38CrossRefGoogle Scholar
2Greenwood, B.M. (2008) Control to elimination: implications for malaria research. Trends in Parasitology 24, 449-454CrossRefGoogle ScholarPubMed
3Collins, W.E. and Barnwell, J.W. (2009) Plasmodium knowlesi: finally being recognized. Journal of Infectious Diseases 199, 1107-1108CrossRefGoogle ScholarPubMed
4Cox-Singh, J. et al. (2008) Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clinical Infectious Diseases 46, 165-171CrossRefGoogle ScholarPubMed
5Jin, Y., Kebaier, C. and Vanderberg, J. (2007) Direct microscopic quantification of dynamics of Plasmodium berghei sporozoite transmission from mosquitoes to mice. Infection and Immunity 75, 5532-5539CrossRefGoogle ScholarPubMed
6Miller, L.H. et al. (2002) The pathogenic basis of malaria. Nature 415, 673-679CrossRefGoogle ScholarPubMed
7Baird, J.K. (2007) Neglect of Plasmodium vivax malaria. Trends in Parasitology 23, 533-539CrossRefGoogle ScholarPubMed
8Marsh, K. and Kinyanjui, S. (2006) Immune effector mechanisms in malaria. Parasite Immunology 28, 51-60CrossRefGoogle ScholarPubMed
9Drakeley, C. et al. (2006) The epidemiology of Plasmodium falciparum gametocytes: weapons of mass dispersion. Trends in Parasitology 22, 424-430CrossRefGoogle ScholarPubMed
10Hoffman, S.L. et al. (2002) Protection of humans against malaria by immunization with radiation- attenuated Plasmodium falciparum sporozoites. Journal of Infectious Diseases 185, 1155-1164CrossRefGoogle ScholarPubMed
11Nussenzweig, R.S. et al. (1967) Protective immunity produced by the injection of x-irradiated sporozoites of Plasmodium berghei. Nature 216, 160-162CrossRefGoogle ScholarPubMed
12Silvie, O. et al. (2002) Effects of irradiation on Plasmodium falciparum sporozoite hepatic development: implications for the design of pre-erythrocytic malaria vaccines. Parasite Immunology 24, 221-223CrossRefGoogle ScholarPubMed
13Doolan, D.L. and Hoffman, S.L. (2000) The complexity of protective immunity against liver-stage malaria. Journal of Immunology 165, 1453-1462CrossRefGoogle ScholarPubMed
14Clyde, D.F. et al. (1973) Immunization of man against sporozite-induced falciparum malaria. American Journal of the Medical Sciences 266, 169-177CrossRefGoogle ScholarPubMed
15Rieckmann, K.H. et al. (1974) Letter: Sporozoite induced immunity in man against an Ethiopian strain of Plasmodium falciparum. Transactions of the Royal Society of Tropical Medicine and Hygiene 68, 258-259CrossRefGoogle ScholarPubMed
16Luke, T.C. and Hoffman, S.L. (2003) Rationale and plans for developing a non-replicating, metabolically active, radiation-attenuated Plasmodium falciparum sporozoite vaccine. Journal of Experimental Biology 206, 3803-3808CrossRefGoogle ScholarPubMed
17Chattopadhyay, R. et al. (2009) The Effects of radiation on the safety and protective efficacy of an attenuated Plasmodium yoelii sporozoite malaria vaccine. Vaccine 27, 3675-3680CrossRefGoogle ScholarPubMed
18Mueller, A.K. et al. (2005) Genetically modified Plasmodium parasites as a protective experimental malaria vaccine. Nature 433, 164-167CrossRefGoogle ScholarPubMed
19Mueller, A.K. et al. (2005) Plasmodium liver stage developmental arrest by depletion of a protein at the parasite-host interface. Proceedings of the National Academy of Sciences of the United States of America 102, 3022-3027CrossRefGoogle ScholarPubMed
20Tarun, A.S. et al. (2007) Protracted sterile protection with Plasmodium yoelii pre-erythrocytic genetically attenuated parasite malaria vaccines is independent of significant liver-stage persistence and is mediated by CD8+ T cells. Journal of Infectious Diseases 196, 608-616CrossRefGoogle ScholarPubMed
21Mikolajczak, S.A. et al. (2007) L-FABP is a critical host factor for successful malaria liver stage development. International Journal for Parasitology 37, 483-489CrossRefGoogle ScholarPubMed
22Good, M.F. (2005) Genetically modified Plasmodium highlights the potential of whole parasite vaccine strategies. Trends in Immunology 26, 295-297CrossRefGoogle ScholarPubMed
23van Dijk, M.R. et al. (2005) Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells. Proceedings of the National Academy of Sciences of the United States of America 102, 12194-12199CrossRefGoogle ScholarPubMed
24Ishino, T., Chinzei, Y. and Yuda, M. (2005) Two proteins with 6-cys motifs are required for malarial parasites to commit to infection of the hepatocyte. Molecular Microbiology 58, 1264-1275CrossRefGoogle ScholarPubMed
25Labaied, M. et al. (2007) Plasmodium yoelii sporozoites with simultaneous deletion of P52 and P36 are completely attenuated and confer sterile immunity against infection. Infection and Immunity 75, 3758-3768CrossRefGoogle ScholarPubMed
26Jobe, O. et al. (2007) Genetically attenuated Plasmodium berghei liver stages induce sterile protracted protection that is mediated by major histocompatibility complex I-dependent interferon- gamma-producing CD8+ T cells. Journal of Infectious Diseases 196, 599-607CrossRefGoogle ScholarPubMed
27Mueller, A.K. et al. (2007) Genetically attenuated Plasmodium berghei liver stages persist and elicit sterile protection primarily via CD8 T cells. American Journal of Pathology 171, 107-115CrossRefGoogle ScholarPubMed
28Aly, A.S. et al. (2008) Targeted deletion of SAP1 abolishes the expression of infectivity factors necessary for successful malaria parasite liver infection. Molecular Microbiology 69, 152-163CrossRefGoogle ScholarPubMed
29van Schaijk, B.C. et al. (2008) Gene disruption of Plasmodium falciparum p52 results in attenuation of malaria liver stage development in cultured primary human hepatocytes. PLoS One 3, e3549CrossRefGoogle ScholarPubMed
30VanBuskirk, K.M. et al. (2009) Preerythrocytic, live-attenuated Plasmodium falciparum vaccine candidates by design. Proceedings of the National Academy of Sciences of the United States of America 106, 13004-13009CrossRefGoogle ScholarPubMed
31Belnoue, E. et al. (2004) Protective T cell immunity against malaria liver stage after vaccination with live sporozoites under chloroquine treatment. Journal of Immunology 172, 2487-2495CrossRefGoogle ScholarPubMed
32Putrianti, E.D. et al. (2009) Vaccine-like immunity against malaria by repeated causal-prophylactic treatment of liver-stage Plasmodium parasites. Journal of Infectious Diseases 199, 899-903CrossRefGoogle ScholarPubMed
33Roestenberg, M. et al. (2009) Protection against a malaria challenge by sporozoite inoculation. New England Journal of Medicine 361, 468-477CrossRefGoogle ScholarPubMed
34Ocana-Morgner, C., Mota, M.M. and Rodriguez, A. (2003) Malaria blood stage suppression of liver stage immunity by dendritic cells. Journal of Experimental Medicine 197, 143-151CrossRefGoogle ScholarPubMed
35Hafalla, J.C. et al. (2007) Efficient development of plasmodium liver stage-specific memory CD8+ T cells during the course of blood-stage malarial infection. Journal of Infectious Diseases 196, 1827-1835CrossRefGoogle ScholarPubMed
36Dame, J.B. et al. (1984) Structure of the gene encoding the immunodominant surface antigen on the sporozoite of the human malaria parasite Plasmodium falciparum. Science 225, 593-599CrossRefGoogle ScholarPubMed
37Enea, V. et al. (1984) DNA cloning of Plasmodium falciparum circumsporozoite gene: amino acid sequence of repetitive epitope. Science 225, 628-630CrossRefGoogle ScholarPubMed
38Stoute, J.A. et al. (1997) A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS,S Malaria Vaccine Evaluation Group. New England Journal of Medicine 336, 86-91CrossRefGoogle ScholarPubMed
39Alonso, P.L. (2006) Malaria: deploying a candidate vaccine (RTS,S/AS02A) for an old scourge of humankind. International Microbiology 9, 83-93Google ScholarPubMed
40Alonso, P.L. et al. (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, 2012-2018CrossRefGoogle ScholarPubMed
41Alonso, P.L. et al. (2004) Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet 364, 1411-1420CrossRefGoogle ScholarPubMed
42Aponte, J.J. et al. (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. Lancet 370, 1543-1551CrossRefGoogle Scholar
43De Becker, G. et al. (2000) The adjuvant monophosphoryl lipid A increases the function of antigen-presenting cells. International Immunology 12, 807-815CrossRefGoogle ScholarPubMed
44Lalvani, A. et al. (1999) Potent induction of focused Th1-type cellular and humoral immune responses by RTS,S/SBAS2, a recombinant Plasmodium falciparum malaria vaccine. Journal of Infectious Diseases 180, 1656-1664CrossRefGoogle ScholarPubMed
45Stoute, J.A. et al. (1998) Long-term efficacy and immune responses following immunization with the RTS,S malaria vaccine. Journal of Infectious Diseases 178, 1139-1144CrossRefGoogle ScholarPubMed
46Wang, R. et al. (2004) Induction in Humans of CD8+ and CD4+ T cell and antibody responses by sequential immunization with malaria DNA and recombinant protein. Journal of Immunology 172, 5561-5569CrossRefGoogle ScholarPubMed
47Bongfen, S.E. et al. (2009) The N-terminal domain of Plasmodium falciparum circumsporozoite protein represents a target of protective immunity. Vaccine 27, 328-335CrossRefGoogle ScholarPubMed
48Dunachie, S.J. et al. (2006) A DNA prime-modified vaccinia virus ankara boost vaccine encoding thrombospondin-related adhesion protein but not circumsporozoite protein partially protects healthy malaria-naive adults against Plasmodium falciparum sporozoite challenge. Infection and Immunity 74, 5933-5942CrossRefGoogle Scholar
49Bejon, P. et al. (2006) A phase 2b randomised trial of the candidate malaria vaccines FP9 ME-TRAP and MVA ME-TRAP among children in Kenya. PLoS Clinical Trials 1, e29CrossRefGoogle ScholarPubMed
50Moorthy, V.S. et al. (2004) A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults. PLoS Medicine 1, e33CrossRefGoogle ScholarPubMed
51Brave, A. et al. (2007) Vaccine delivery methods using viral vectors. Molecular Pharmaceutics 4, 18-32CrossRefGoogle ScholarPubMed
52Ophorst, O.J. et al. (2007) Increased immunogenicity of recombinant Ad35-based malaria vaccine through formulation with aluminium phosphate adjuvant. Vaccine 25, 6501-6510CrossRefGoogle ScholarPubMed
53Vogels, R. et al. (2007) High-level expression from two independent expression cassettes in replication-incompetent adenovirus type 35 vector. Journal of General Virology 88, 2915-2924CrossRefGoogle ScholarPubMed
54Shott, J.P. et al. (2008) Adenovirus 5 and 35 vectors expressing Plasmodium falciparum circumsporozoite surface protein elicit potent antigen-specific cellular IFN-gamma and antibody responses in mice. Vaccine 26, 2818-2823CrossRefGoogle ScholarPubMed
55Reyes-Sandoval, A. et al. (2008) Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei. European Journal of Immunology 38, 732-741CrossRefGoogle ScholarPubMed
56Buchbinder, S.P. et al. (2008) Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372, 1881-1893CrossRefGoogle ScholarPubMed
57Kumar, K.A. et al. (2006) The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites. Nature 444, 937-940CrossRefGoogle ScholarPubMed
58Gruner, A.C. et al. (2007) Sterile protection against malaria is independent of immune responses to the circumsporozoite protein. PLoS One 2, e1371CrossRefGoogle Scholar
59Chakravarty, S. et al. (2007) CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes. Nature Medicine 13, 1035-1041CrossRefGoogle ScholarPubMed
60Bucci, K. et al. (2000) Influence of age and HLA type on interferon-gamma (IFN-gamma) responses to a naturally occurring polymorphic epitope of Plasmodium falciparum liver stage antigen-1 (LSA-1). Clinical and Experimental Immunology 122, 94-100CrossRefGoogle ScholarPubMed
61Erunkulu, O.A. et al. (1992) Severe malaria in Gambian children is not due to lack of previous exposure to malaria. Clinical and Experimental Immunology 89, 296-300CrossRefGoogle Scholar
62Kurtis, J.D. et al. (1999) Interleukin-10 responses to liver-stage antigen 1 predict human resistance to Plasmodium falciparum. Infection and Immunity 67, 3424-3429CrossRefGoogle ScholarPubMed
63Rodriguez, A. et al. (2008) Impact of recombinant adenovirus serotype 35 priming versus boosting of a Plasmodium falciparum protein: characterization of T- and B-cell responses to liver-stage antigen 1. Infection and Immunity 76, 1709-1718CrossRefGoogle ScholarPubMed
64Cummings, J.F. et al. (2009) 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 doi:10.1016/j.vaccine.2009.08.046.Google Scholar
65Daubersies, P. et al. (2000) Protection against Plasmodium falciparum malaria in chimpanzees by immunization with the conserved pre-erythrocytic liver-stage antigen 3. Nature Medicine 6, 1258-1263CrossRefGoogle ScholarPubMed
66Perlaza, B.L. et al. (2008) Protection against Plasmodium falciparum challenge induced in Aotus monkeys by liver-stage antigen-3-derived long synthetic peptides. European Journal of Immunology 38, 2610-2615CrossRefGoogle ScholarPubMed
67Perlaza, B.L. et al. (2003) Immunogenicity and protective efficacy of Plasmodium falciparum liver-stage Ag-3 in Aotus lemurinus griseimembra monkeys. European Journal of Immunology 33, 1321-1327CrossRefGoogle ScholarPubMed
68Daubersies, P. et al. (2008) Genetic immunisation by liver stage antigen 3 protects chimpanzees against malaria despite low immune responses. PLoS One 3, e2659CrossRefGoogle ScholarPubMed
69Thompson, F.M. et al. (2008) Evidence of blood stage efficacy with a virosomal malaria vaccine in a phase IIa clinical trial. PLoS One 3, e1493CrossRefGoogle Scholar
70Doolan, D.L. et al. (2003) Identification of Plasmodium falciparum antigens by antigenic analysis of genomic and proteomic data. Proceedings of the National Academy of Sciences of the United States of America 100, 9952-9957CrossRefGoogle ScholarPubMed
71Draper, S.J. et al. (2009) Recombinant viral vaccines expressing merozoite surface protein-1 induce antibody- and T cell-mediated multistage protection against malaria. Cell Host and Microbe 5, 95-105CrossRefGoogle Scholar
72Renia, L. et al. (1997) Immunization with a recombinant C-terminal fragment of Plasmodium yoelii merozoite surface protein 1 protects mice against homologous but not heterologous P. yoelii sporozoite challenge. Infection and Immunity 65, 4419-4423CrossRefGoogle Scholar
73Kumar, K.A. et al. (2009) onserved protective mechanisms in radiation and genetically attenuated uis3(−) and uis4(−) plasmodium sporozoites. PLoS One 4, e4480CrossRefGoogle Scholar
74Tsuji, M. and Zavala, F. (2003) T cells as mediators of protective immunity against liver stages of Plasmodium. Trends in Parasitology 19, 88-93CrossRefGoogle ScholarPubMed
75Overstreet, M.G. et al. (2008) Protective CD8 T cells against Plasmodium liver stages: immunobiology of an 'unnatural' immune response. Immunological Reviews 225, 272-283CrossRefGoogle ScholarPubMed
76Carvalho, L.H. et al. (2002) IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages. Nature Medicine 8, 166-170CrossRefGoogle Scholar
77Weiss, W.R. et al. (1988) CD8+ T cells (cytotoxic/suppressors) are required for protection in mice immunized with malaria sporozoites. Proceedings of the National Academy of Sciences of the United States of America 85, 573-576CrossRefGoogle ScholarPubMed
78White, K.L., Snyder, H.L. and Krzych, U. (1996) MHC class I-dependent presentation of exoerythrocytic antigens to CD8+ T lymphocytes is required for protective immunity against Plasmodium berghei. Journal of Immunology 156, 3374-3381CrossRefGoogle ScholarPubMed
79Rodrigues, M.M. et al. (1991) CD8+ cytolytic T cell clones derived against the Plasmodium yoelii circumsporozoite protein protect against malaria. International Immunology 3, 579-585CrossRefGoogle ScholarPubMed
80Romero, P. et al. (1989) Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature 341, 323-326CrossRefGoogle ScholarPubMed
81Weiss, W.R. et al. (1992) A T cell clone directed at the circumsporozoite protein which protects mice against both Plasmodium yoelii and Plasmodium berghei. Journal of Immunology 149, 2103-2109CrossRefGoogle Scholar
82Wizel, B. et al. (1995) Irradiated sporozoite vaccine induces HLA-B8-restricted cytotoxic T lymphocyte responses against two overlapping epitopes of the Plasmodium falciparum sporozoite surface protein 2. Journal of Experimental Medicine 182, 1435-1445CrossRefGoogle ScholarPubMed
83Bongfen, S.E. et al. (2007) Plasmodium berghei-infected primary hepatocytes process and present the circumsporozoite protein to specific CD8+ T cells in vitro. Journal of Immunology 178, 7054-7063CrossRefGoogle ScholarPubMed
84Weiss, W.R. et al. (1990) Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes. Journal of Experimental Medicine 171, 763-773CrossRefGoogle ScholarPubMed
85Klotz, F.W. et al. (1995) Co-localization of inducible-nitric oxide synthase and Plasmodium berghei in hepatocytes from rats immunized with irradiated sporozoites. Journal of Immunology 154, 3391-3395CrossRefGoogle ScholarPubMed
86Schofield, L. et al. (1987) Interferon-gamma inhibits the intrahepatocytic development of malaria parasites in vitro. Journal of Immunology 139, 2020-2025CrossRefGoogle ScholarPubMed
87Seguin, M.C. et al. (1994) Induction of nitric oxide synthase protects against malaria in mice exposed to irradiated Plasmodium berghei infected mosquitoes: involvement of interferon gamma and CD8+ T cells. Journal of Experimental Medicine 180, 353-358CrossRefGoogle ScholarPubMed
88Rodrigues, E.G. et al. (2000) Interferon-gamma-independent CD8+ T cell-mediated protective anti-malaria immunity elicited by recombinant adenovirus. Parasite Immunology 22, 157-160CrossRefGoogle ScholarPubMed
89Chakravarty, S. et al. (2008) Effector CD8+ T lymphocytes against liver stages of Plasmodium yoelii do not require gamma interferon for antiparasite activity. Infection and Immunity 76, 3628-3631CrossRefGoogle Scholar
90Trimnell, A. et al. (2009) Genetically attenuated parasite vaccines induce contact-dependent CD8+ T cell killing of Plasmodium yoelii liver stage-infected hepatocytes. Journal of Immunology 183, 5870-5878CrossRefGoogle ScholarPubMed
91Jobe, O. et al. (2009) Immunization with radiation-attenuated Plasmodium berghei sporozoites induces liver cCD8alpha + DC that activate CD8 + T cells against liver-stage malaria. PLoS One 4, e5075CrossRefGoogle ScholarPubMed
92Plebanski, M. et al. (2005) Direct processing and presentation of antigen from malaria sporozoites by professional antigen-presenting cells in the induction of CD8 T-cell responses. Immunology and Cell Biology 83, 307-312CrossRefGoogle ScholarPubMed
93Bongfen, S.E. et al. (2008) Processing of the circumsporozoite protein in infected hepatocytes is not dependent on aspartic proteases. Parasite Immunology 30, 375-378CrossRefGoogle Scholar
94Usynin, I., Klotz, C. and Frevert, U. (2007) Malaria circumsporozoite protein inhibits the respiratory burst in Kupffer cells. Cellular Microbiology 9, 2610-2628CrossRefGoogle ScholarPubMed
95Singh, A.P. et al. (2007) Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite. Cell 131, 492-504CrossRefGoogle ScholarPubMed
96Todryk, S.M. et al. (2008) Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans. PLoS One 3, e2027CrossRefGoogle Scholar
97Krzych, U. and Schwenk, J. (2005) The dissection of CD8 T cells during liver-stage infection. Current Topics in Microbiology and Immunology 297, 1-24Google ScholarPubMed
98Berenzon, D. et al. (2003) Protracted protection to Plasmodium berghei malaria is linked to functionally and phenotypically heterogeneous liver memory CD8+ T cells. Journal of Immunology 171, 2024-2034CrossRefGoogle ScholarPubMed
99Schmidt, N.W. et al. (2008) Memory CD8 T cell responses exceeding a large but definable threshold provide long-term immunity to malaria. Proceedings of the National Academy of Sciences of the United States of America 105, 14017-14022CrossRefGoogle ScholarPubMed
100Dvorak, J.A. et al. (1975) Invasion of erythrocytes by malaria merozoites. Science 187, 748-750CrossRefGoogle ScholarPubMed
101Marsh, K. and Snow, R.W. (1997) Host-parasite interaction and morbidity in malaria endemic areas. Philosophical Transactions of the Royal Society of London Series B Biological Sciences 352, 1385-1394CrossRefGoogle ScholarPubMed
102Cohen, S., Mc, G.I. and Carrington, S. (1961) Gamma-globulin and acquired immunity to human malaria. Nature 192, 733-737CrossRefGoogle ScholarPubMed
103Sabchareon, A. et al. (1991) Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria. American Journal of Tropical Medicine and Hygiene 45, 297-308CrossRefGoogle ScholarPubMed
104Gilson, P.R. and Crabb, B.S. (2009) Morphology and kinetics of the three distinct phases of red blood cell invasion by Plasmodium falciparum merozoites. International Journal for Parasitology 39, 91-96CrossRefGoogle ScholarPubMed
105Goel, V.K. et al. (2003) Band 3 is a host receptor binding merozoite surface protein 1 during the Plasmodium falciparum invasion of erythrocytes. Proceedings of the National Academy of Sciences of the United States of America 100, 5164-5169CrossRefGoogle ScholarPubMed
106Mitchell, G.H. et al. (2004) Apical membrane antigen 1, a major malaria vaccine candidate, mediates the close attachment of invasive merozoites to host red blood cells. Infection and Immunity 72, 154-158CrossRefGoogle Scholar
107Miller, L.H. et al. (1979) Interaction between cytochalasin B-treated malarial parasites and erythrocytes. Attachment and junction formation. Journal of Experimental Medicine 149, 172-184CrossRefGoogle ScholarPubMed
108Singh, A.P. et al. (2005) Targeted deletion of Plasmodium knowlesi Duffy binding protein confirms its role in junction formation during invasion. Molecular Microbiology 55, 1925-1934CrossRefGoogle ScholarPubMed
109Holder, A.A. et al. (1987) Processing of the precursor to the major merozoite surface antigens of Plasmodium falciparum. Parasitology 94 (Pt 2), 199-208CrossRefGoogle Scholar
110Lyon, J.A. et al. (1987) Monoclonal antibody characterization of the 195-kilodalton major surface glycoprotein of Plasmodium falciparum malaria schizonts and merozoites: identification of additional processed products and a serotype-restricted repetitive epitope. Journal of Immunology 138, 895-901CrossRefGoogle Scholar
111Kauth, C.W. et al. (2003) The merozoite surface protein 1 complex of human malaria parasite Plasmodium falciparum: interactions and arrangements of subunits. Journal of Biological Chemistry 278, 22257-22264CrossRefGoogle ScholarPubMed
112Kauth, C.W. et al. (2006) Interactions between merozoite surface proteins 1, 6, and 7 of the malaria parasite Plasmodium falciparum. Journal of Biological Chemistry 281, 31517-31527Google Scholar
113Blackman, M.J. and Holder, A.A. (1992) Secondary processing of the Plasmodium falciparum merozoite surface protein-1 (MSP1) by a calcium-dependent membrane-bound serine protease: shedding of MSP133 as a noncovalently associated complex with other fragments of the MSP1. Molecular and Biochemical Parasitology 50, 307-315CrossRefGoogle ScholarPubMed
114Blackman, M.J. et al. (1991) Proteolytic processing of the Plasmodium falciparum merozoite surface protein-1 produces a membrane-bound fragment containing two epidermal growth factor-like domains. Molecular and Biochemical Parasitology 49, 29-33CrossRefGoogle ScholarPubMed
115Angov, E. et al. (2003) Development and pre-clinical analysis of a Plasmodium falciparum Merozoite Surface Protein-1(42) malaria vaccine. Molecular and Biochemical Parasitology 128, 195-204CrossRefGoogle ScholarPubMed
116Blackman, M.J. et al. (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. Journal of Experimental Medicine 172, 379-382CrossRefGoogle ScholarPubMed
117John, C.C. et al. (2004) Evidence that invasion-inhibitory antibodies specific for the 19-kDa fragment of merozoite surface protein-1 (MSP-1 19) can play a protective role against blood-stage Plasmodium falciparum infection in individuals in a malaria endemic area of Africa. Journal of Immunology 173, 666-672CrossRefGoogle Scholar
118Ling, I.T., Ogun, S.A. and Holder, A.A. (1994) Immunization against malaria with a recombinant protein. Parasite Immunology 16, 63-67CrossRefGoogle ScholarPubMed
119Majarian, W.R. et al. (1984) Passive immunization against murine malaria with an IgG3 monoclonal antibody. Journal of Immunology 132, 3131-3137CrossRefGoogle ScholarPubMed
120O'Donnell, R.A. et al. (2001) Antibodies against merozoite surface protein (MSP)-1(19) are a major component of the invasion-inhibitory response in individuals immune to malaria. Journal of Experimental Medicine 193, 1403-1412CrossRefGoogle Scholar
121McIntosh, R.S. et al. (2007) The importance of human FcgammaRI in mediating protection to malaria. PLoS Pathogens 3, e72CrossRefGoogle ScholarPubMed
122Bergmann-Leitner, E.S. et al. (2006) Critical evaluation of different methods for measuring the functional activity of antibodies against malaria blood stage antigens. American Journal of Tropical Medicine and Hygiene 75, 437-442CrossRefGoogle ScholarPubMed
123Singh, S. et al. (2006) Immunity to recombinant Plasmodium falciparum merozoite surface protein 1 (MSP1): protection in Aotus nancymai monkeys strongly correlates with anti-MSP1 antibody titer and in vitro parasite-inhibitory activity. Infection and Immunity 74, 4573-4580CrossRefGoogle ScholarPubMed
124Woehlbier, U. et al. (2006) Analysis of antibodies directed against merozoite surface protein 1 of the human malaria parasite Plasmodium falciparum. Infection and Immunity 74, 1313-1322CrossRefGoogle ScholarPubMed
125Lyon, J.A. et al. (2008) Protection induced by Plasmodium falciparum MSP1(42) is strain-specific, antigen and adjuvant dependent, and correlates with antibody responses. PLoS One 3, e2830CrossRefGoogle ScholarPubMed
126Ockenhouse, C.F. et al. (2006) Phase I safety and immunogenicity trial of FMP1/AS02A, a Plasmodium falciparum MSP-1 asexual blood stage vaccine. Vaccine 24, 3009-3017CrossRefGoogle ScholarPubMed
127Stoute, J.A. et al. (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, 176-184CrossRefGoogle ScholarPubMed
128Thera, M.A. et al. (2006) Safety and allele-specific immunogenicity of a malaria vaccine in Malian adults: results of a phase I randomized trial. PLoS Clinical Trials 1, e34CrossRefGoogle ScholarPubMed
129Ogutu, B.R. et al. (2009) Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS One 4, e4708CrossRefGoogle ScholarPubMed
130Healer, J. et al. (2002) Independent translocation of two micronemal proteins in developing Plasmodium falciparum merozoites. Infection and Immunity 70, 5751-5758CrossRefGoogle ScholarPubMed
131Narum, D.L. and Thomas, A.W. (1994) Differential localization of full-length and processed forms of PF83/AMA-1 an apical membrane antigen of Plasmodium falciparum merozoites. Molecular and Biochemical Parasitology 67, 59-68CrossRefGoogle ScholarPubMed
132Cao, J. et al. (2009) Rhoptry neck protein RON2 forms a complex with microneme protein AMA1 in Plasmodium falciparum merozoites. Parasitology International 58, 29-35CrossRefGoogle ScholarPubMed
133Collins, C.R. et al. (2009) An inhibitory antibody blocks interactions between components of the malarial invasion machinery. PLoS Pathogens 5, e1000273CrossRefGoogle ScholarPubMed
134Alexander, D.L. et al. (2005) Identification of the moving junction complex of Toxoplasma gondii: a collaboration between distinct secretory organelles. PLoS Pathogens 1, e17CrossRefGoogle ScholarPubMed
135Dutta, S. et al. (2005) Mode of action of invasion-inhibitory antibodies directed against apical membrane antigen 1 of Plasmodium falciparum. Infection and Immunity 73, 2116-2122CrossRefGoogle ScholarPubMed
136Dutta, S. et al. (2003) Invasion-inhibitory antibodies inhibit proteolytic processing of apical membrane antigen 1 of Plasmodium falciparum merozoites. Proceedings of the National Academy of Sciences of the United States of America 100, 12295-12300CrossRefGoogle ScholarPubMed
137Hodder, A.N., Crewther, P.E. and Anders, R.F. (2001) Specificity of the protective antibody response to apical membrane antigen 1. Infection and Immunity 69, 3286-3294CrossRefGoogle ScholarPubMed
138Kennedy, M.C. et al. (2002) In vitro studies with recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1): production and activity of an AMA1 vaccine and generation of a multiallelic response. Infection and Immunity 70, 6948-6960CrossRefGoogle ScholarPubMed
139Kocken, C.H. et al. (2002) High-level expression of the malaria blood-stage vaccine candidate Plasmodium falciparum apical membrane antigen 1 and induction of antibodies that inhibit erythrocyte invasion. Infection and Immunity 70, 4471-4476CrossRefGoogle ScholarPubMed
140Dicko, A. et al. (2008) Phase 1 study of a combination AMA1 blood stage malaria vaccine in Malian children. PLoS One 3, e1563CrossRefGoogle ScholarPubMed
141Spring, M.D. et al. (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, e5254CrossRefGoogle ScholarPubMed
142Sagara, I. et al. (2009) A randomized controlled phase 2 trial of the blood stage AMA1-C1/Alhydrogel malaria vaccine in children in Mali. Vaccine 27, 3090-3098CrossRefGoogle ScholarPubMed
143Hu, J. et al. (2008) Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 chimeric protein formulated in montanide ISA 720 in healthy adults. PLoS One 3, e1952CrossRefGoogle ScholarPubMed
144Miller, L.H. et al. (1976) The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. New England Journal of Medicine 295, 302-304CrossRefGoogle ScholarPubMed
145Fang, X.D. et al. (1991) Cloning of the Plasmodium vivax Duffy receptor. Molecular and Biochemical Parasitology 44, 125-132CrossRefGoogle ScholarPubMed
146Chitnis, C.E. and Miller, L.H. (1994) Identification of the erythrocyte binding domains of Plasmodium vivax and Plasmodium knowlesi proteins involved in erythrocyte invasion. Journal of Experimental Medicine 180, 497-506CrossRefGoogle ScholarPubMed
147Sim, B.K. et al. (1994) Receptor and ligand domains for invasion of erythrocytes by Plasmodium falciparum. Science 264, 1941-1944CrossRefGoogle ScholarPubMed
148Cowman, A.F. and Crabb, B.S. (2006) Invasion of red blood cells by malaria parasites. Cell 124, 755-766CrossRefGoogle ScholarPubMed
149Adams, J.H. et al. (1990) The Duffy receptor family of Plasmodium knowlesi is located within the micronemes of invasive malaria merozoites. Cell 63, 141-153CrossRefGoogle ScholarPubMed
150Singh, S.K. et al. (2006) Structural basis for Duffy recognition by the malaria parasite Duffy-binding-like domain. Nature 439, 741-744CrossRefGoogle ScholarPubMed
151Chitnis, C.E. and Sharma, A. (2008) Targeting the Plasmodium vivax Duffy-binding protein. Trends in Parasitology 24, 29-34CrossRefGoogle ScholarPubMed
152Tsuboi, T. et al. (1994) Natural variation within the principal adhesion domain of the Plasmodium vivax duffy binding protein. Infection and Immunity 62, 5581-5586CrossRefGoogle ScholarPubMed
153Xainli, J., Adams, J.H. and King, C.L. (2000) The erythrocyte binding motif of Plasmodium vivax duffy binding protein is highly polymorphic and functionally conserved in isolates from Papua New Guinea. Molecular and Biochemical Parasitology 111, 253-260CrossRefGoogle ScholarPubMed
154VanBuskirk, K.M. et al. (2004) Antigenic drift in the ligand domain of Plasmodium vivax duffy binding protein confers resistance to inhibitory antibodies. Journal of Infectious Diseases 190, 1556-1562CrossRefGoogle ScholarPubMed
155King, C.L. et al. (2008) Naturally acquired Duffy-binding protein-specific binding inhibitory antibodies confer protection from blood-stage Plasmodium vivax infection. Proceedings of the National Academy of Sciences of the United States of America 105, 8363-8368CrossRefGoogle ScholarPubMed
156Singh, S. et al. (2001) Biochemical, biophysical, and functional characterization of bacterially expressed and refolded receptor binding domain of Plasmodium vivax duffy-binding protein. Journal of Biological Chemistry 276, 17111-17116CrossRefGoogle ScholarPubMed
157Devi, Y.S. et al. (2007) Immunogenicity of Plasmodium vivax combination subunit vaccine formulated with human compatible adjuvants in mice. Vaccine 25, 5166-5174CrossRefGoogle ScholarPubMed
158Michon, P., Fraser, T. and Adams, J.H. (2000) Naturally acquired and vaccine-elicited antibodies block erythrocyte cytoadherence of the Plasmodium vivax Duffy binding protein. Infection and Immunity 68, 3164-3171CrossRefGoogle ScholarPubMed
159Yazdani, S.S. et al. (2004) Evaluation of immune responses elicited in mice against a recombinant malaria vaccine based on Plasmodium vivax Duffy binding protein. Vaccine 22, 3727-3737CrossRefGoogle ScholarPubMed
160Grimberg, B.T. et al. (2007) Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. PLoS Medicine 4, e337CrossRefGoogle ScholarPubMed
161Arevalo-Herrera, M. et al. (2005) Immunogenicity and protective efficacy of recombinant vaccine based on the receptor-binding domain of the Plasmodium vivax Duffy Binding protein in Aotus monkeys. American Journal of Tropical Medicine and Hygiene 73, 25-31CrossRefGoogle ScholarPubMed
162Kyes, S., Horrocks, P. and Newbold, C. (2001) Antigenic variation at the infected red cell surface in malaria. Annual Review of Microbiology 55, 673-707CrossRefGoogle ScholarPubMed
163Kraemer, S.M. and Smith, J.D. (2006) A family affair: var genes, PfEMP1 binding, and malaria disease. Current Opinion in Microbiology 9, 374-380CrossRefGoogle ScholarPubMed
164Udomsangpetch, R. et al. (2002) Febrile temperatures induce cytoadherence of ring-stage Plasmodium falciparum-infected erythrocytes. Proceedings of the National Academy of Sciences of the United States of America 99, 11825-11829CrossRefGoogle ScholarPubMed
165Baruch, D.I. (1999) Adhesive receptors on malaria-parasitized red cells. Baillieres Best Pract Res Clinics in Haematology 12, 747-761CrossRefGoogle ScholarPubMed
166Su, X.Z. et al. (1995) The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82, 89-100CrossRefGoogle ScholarPubMed
167Gardner, M.J. et al. (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419, 498-511CrossRefGoogle ScholarPubMed
168Smith, J.D. et al. (1995) Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82, 101-110CrossRefGoogle ScholarPubMed
169Brabin, B.J. et al. (2004) The sick placenta - the role of malaria. Placenta 25, 359-378CrossRefGoogle ScholarPubMed
170Steketee, R.W. et al. (2001) The burden of malaria in pregnancy in malaria-endemic areas. American Journal of Tropical Medicine and Hygiene 64, 28-35CrossRefGoogle ScholarPubMed
171Duffy, M.F. et al. (2006) Transcribed var genes associated with placental malaria in Malawian women. Infection and Immunity 74, 4875-4883CrossRefGoogle ScholarPubMed
172Magistrado, P. et al. (2008) VAR2CSA expression on the surface of placenta-derived Plasmodium falciparum-infected erythrocytes. Journal of Infectious Diseases 198, 1071-1074CrossRefGoogle ScholarPubMed
173Salanti, A. et al. (2003) Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria. Molecular Microbiology 49, 179-191CrossRefGoogle ScholarPubMed
174Tuikue Ndam, N.G. et al. (2005) High level of var2csa transcription by Plasmodium falciparum isolated from the placenta. Journal of Infectious Diseases 192, 331-335CrossRefGoogle ScholarPubMed
175Trimnell, A.R. et al. (2006) Global genetic diversity and evolution of var genes associated with placental and severe childhood malaria. Molecular and Biochemical Parasitology 148, 169-180CrossRefGoogle ScholarPubMed
176Avril, M. et al. (2008) Evidence for globally shared, cross-reacting polymorphic epitopes in the pregnancy-associated malaria vaccine candidate VAR2CSA. Infection and Immunity 76, 1791-1800CrossRefGoogle ScholarPubMed
177Barfod, L. et al. (2006) Baculovirus-expressed constructs induce immunoglobulin G that recognizes VAR2CSA on Plasmodium falciparum-infected erythrocytes. Infection and Immunity 74, 4357-4360CrossRefGoogle ScholarPubMed
178Fernandez, P. et al. (2008) Var2CSA DBL6-epsilon domain expressed in HEK293 induces limited cross-reactive and blocking antibodies to CSA binding parasites. Malaria Journal 7, 170CrossRefGoogle ScholarPubMed
179Nielsen, M.A. et al. (2009) Induction of adhesion-inhibitory antibodies against placental Plasmodium falciparum parasites by using single domains of VAR2CSA. Infection and Immunity 77, 2482-2487CrossRefGoogle ScholarPubMed
180Oleinikov, A.V. et al. (2008) VAR2CSA domains expressed in Escherichia coli induce cross-reactive antibodies to native protein. Journal of Infectious Diseases 197, 1119-1123CrossRefGoogle ScholarPubMed
181Beeson, J.G. et al. (2006) Antigenic differences and conservation among placental Plasmodium falciparum-infected erythrocytes and acquisition of variant-specific and cross-reactive antibodies. Journal of Infectious Diseases 193, 721-730CrossRefGoogle ScholarPubMed
182Bockhorst, J. et al. (2007) Structural polymorphism and diversifying selection on the pregnancy malaria vaccine candidate VAR2CSA. Molecular and Biochemical Parasitology 155, 103-112CrossRefGoogle ScholarPubMed
183Fried, M. et al. (1998) Maternal antibodies block malaria. Nature 395, 851-852CrossRefGoogle ScholarPubMed
184Barfod, L. et al. (2007) Human pregnancy-associated malaria-specific B cells target polymorphic, conformational epitopes in VAR2CSA. Molecular Microbiology 63, 335-347CrossRefGoogle ScholarPubMed
185Andersen, P. et al. (2008) Structural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA. PLoS Pathogens 4, e42CrossRefGoogle ScholarPubMed
186Duffy, P.E. and Fried, M. (2003) Antibodies that inhibit Plasmodium falciparum adhesion to chondroitin sulfate A are associated with increased birth weight and the gestational age of newborns. Infection and Immunity 71, 6620-6623CrossRefGoogle ScholarPubMed
187O'Neil-Dunne, I. et al. (2001) Gravidity-dependent production of antibodies that inhibit binding of Plasmodium falciparum-infected erythrocytes to placental chondroitin sulfate proteoglycan during pregnancy. Infection and Immunity 69, 7487-7492CrossRefGoogle ScholarPubMed
188Ricke, C.H. et al. (2000) Plasma antibodies from malaria-exposed pregnant women recognize variant surface antigens on Plasmodium falciparum-infected erythrocytes in a parity-dependent manner and block parasite adhesion to chondroitin sulfate A. Journal of Immunology 165, 3309-3316CrossRefGoogle Scholar
189Jaworowski, A. et al. (2009) Relationship between human immunodeficiency virus type 1 coinfection, anemia, and levels and function of antibodies to variant surface antigens in pregnancy-associated malaria. Clinical and Vaccine Immunology 16, 312-319CrossRefGoogle ScholarPubMed
190Keen, J. et al. (2007) HIV impairs opsonic phagocytic clearance of pregnancy-associated malaria parasites. PLoS Medicine 4, e181CrossRefGoogle ScholarPubMed
191Mount, A.M. et al. (2004) Impairment of humoral immunity to Plasmodium falciparum malaria in pregnancy by HIV infection. Lancet 363, 1860-1867CrossRefGoogle ScholarPubMed
192Staalsoe, T. et al. (2004) Variant surface antigen-specific IgG and protection against clinical consequences of pregnancy-associated Plasmodium falciparum malaria. Lancet 363, 283-289CrossRefGoogle ScholarPubMed
193Krishnegowda, G. et al. (2005) Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: cell signaling receptors, glycosylphosphatidylinositol (GPI) structural requirement, and regulation of GPI activity. Journal of Biological Chemistry 280, 8606-8616CrossRefGoogle ScholarPubMed
194Schofield, L. and Hackett, F. (1993) Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites. Journal of Experimental Medicine 177, 145-153CrossRefGoogle ScholarPubMed
195Parroche, P. et al. (2007) Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9. Proceedings of the National Academy of Sciences of the United States of America 104, 1919-1924CrossRefGoogle ScholarPubMed
196Grau, G.E. et al. (1989) Tumor necrosis factor and disease severity in children with falciparum malaria. New England Journal of Medicine 320, 1586-1591CrossRefGoogle ScholarPubMed
197Kwiatkowski, D. et al. (1990) TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 336, 1201-1204CrossRefGoogle ScholarPubMed
198Schofield, L. et al. (1996) Glycosylphosphatidylinositol toxin of Plasmodium up-regulates intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression in vascular endothelial cells and increases leukocyte and parasite cytoadherence via tyrosine kinase-dependent signal transduction. Journal of Immunology 156, 1886-1896CrossRefGoogle ScholarPubMed
199Schofield, L. et al. (2002) Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. Nature 418, 785-789CrossRefGoogle Scholar
200Tarun, A.S. et al. (2006) Quantitative isolation and in vivo imaging of malaria parasite liver stages. International Journal for Parasitology 36, 1283-1293CrossRefGoogle ScholarPubMed
201Tarun, A.S. et al. (2008) A combined transcriptome and proteome survey of malaria parasite liver stages. Proceedings of the National Academy of Sciences of the United States of America 105, 305-310CrossRefGoogle ScholarPubMed
202Corradin, G. (2007) Peptide based malaria vaccine development: personal considerations. Microbes and Infection 9, 767-771CrossRefGoogle ScholarPubMed
203Haddad, D. et al. (2004) Novel antigen identification method for discovery of protective malaria antigens by rapid testing of DNA vaccines encoding exons from the parasite genome. Infection and Immunity 72, 1594-1602CrossRefGoogle ScholarPubMed
204Wang, R. et al. (2005) Immune responses to Plasmodium vivax pre-erythrocytic stage antigens in naturally exposed Duffy-negative humans: a potential model for identification of liver-stage antigens. European Journal of Immunology 35, 1859-1868CrossRefGoogle ScholarPubMed
205Greenwood, B., Marsh, K. and Snow, R. (1991) Why do some African children develop severe malaria? Parasitology Today 7, 277-281CrossRefGoogle ScholarPubMed
206Koutsky, L.A. et al. (2002) A controlled trial of a human papillomavirus type 16 vaccine. New England Journal of Medicine 347, 1645-1651CrossRefGoogle ScholarPubMed
207Di Giulio, G. et al. (2009) Live immunization against East Coast fever-current status. Trends in Parasitology 25, 85-92CrossRefGoogle ScholarPubMed

Further reading, resources and contacts:

NIAID malaria research website:

Irwin Sherman (2009). The elusive malaria vaccine: miracle or mirage. ASM Press.Google Scholar
Vanderberg, J.P. (2009) Reflections on early malaria vaccine studies, the first successful human malaria vaccination, and beyond. Vaccine 27, 2-9CrossRefGoogle ScholarPubMed
Dinglasan, R.R. and Jacobs-Lorena, M. (2008) Flipping the paradigm on malaria transmission-blocking vaccines. Trends in Parasitology 24, 364-370CrossRefGoogle ScholarPubMed
Lavazec, C. and Bourgouin, C. (2008) Mosquito-based transmission blocking vaccines for interrupting Plasmodium development. Microbes and Infection 10, 845-849CrossRefGoogle ScholarPubMed
Irwin Sherman (2009). The elusive malaria vaccine: miracle or mirage. ASM Press.Google Scholar
Vanderberg, J.P. (2009) Reflections on early malaria vaccine studies, the first successful human malaria vaccination, and beyond. Vaccine 27, 2-9CrossRefGoogle ScholarPubMed
Dinglasan, R.R. and Jacobs-Lorena, M. (2008) Flipping the paradigm on malaria transmission-blocking vaccines. Trends in Parasitology 24, 364-370CrossRefGoogle ScholarPubMed
Lavazec, C. and Bourgouin, C. (2008) Mosquito-based transmission blocking vaccines for interrupting Plasmodium development. Microbes and Infection 10, 845-849CrossRefGoogle ScholarPubMed