Safety, tolerability, and antibody responses in humans after sequential immunization with a PfCSP DNA vaccine followed by the recombinant protein vaccine RTS,S/AS02A

Abstract

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 IFNγ 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 + IFNγ-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 P. falciparum CSP DNA vaccine (VCL-2510) and to naı̈ve 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.