Journal
VACCINE
Volume 22, Issue 13-14, Pages 1592-1603Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2004.01.031
Keywords
DNA vaccine; RTS,S; malaria; clinical trial; sequential immunization; prime-boost; circumsporozoite protein; Plasmodium falciparum; prime boost immunization; heterologous prime boost immunization
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Optimal protection against malaria may require induction of high levels of protective antibody and CD8+ and CD4+ T cell responses. In humans, malaria DNA vaccines elicit CD8+ cytotoxic T cells (CTL) and IFNgamma responses as measured by short-term (ex vivo) ELISPOT assays, and recombinant proteins elicit antibodies and excellent T cell responses, but no CD8+ CTL or CD8+ IFNgamma-producing cells as measured by ex vivo ELISPOT. Priming with DNA and boosting with recombinant pox virus elicits much better T cell responses than DNA alone, but not antibody responses. In an attempt to elicit antibodies and enhanced T cell responses, we administered RTS,S/AS02A, a partially protective Plasmodium falciparum recombinant circumsporozoite protein (CSP) vaccine in adjuvant, to volunteers previously immunized with a R falciparum CSP DNA vaccine (VCL-2510) and to naive volunteers. This vaccine regimen was well tolerated and safe. The volunteers who received RTS,S/AS02A alone had, as expected, antibody and CD4+ T cell responses, but no CD8+ T cell responses. Volunteers who received PfCSP DNA followed by RTS,S/AS02A had antibody and CD8+ and CD4+ T cell responses (Wang et al., submitted). Sequential immunization with DNA and recombinant protein, also called heterologous prime-boost, led to enhanced immune responses as compared to DNA or recombinant protein alone, suggesting that it might provide enhanced protective immunity. (C) 2004 Elsevier Ltd. All rights reserved.
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