Epstein, J. E., Charoenvit, Y., Kester, K. E., Wang, R., Newcomer, R., Fitzpatrick, S., Richie, T. L., Tornieporth, N., Heppner, D. G., Ockenhouse, C., Majam, V., Holland, C., Abot, E., Ganeshan, H., Berzins, M., Jones, T., Freydberg, C. N., Ng, J., Norman, J., Carucci, D. J., Cohen, J., Hoffman, S. L.
Safety, Tolerability, and Antibody Responses In Humans After Sequential Immunization With a PfCSP DNA Vaccine Followed by the Recombinant Protein Vaccine RTS,S/AS02A
Vaccine. 2004 Apr 16; 22(13): 1592-603.
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 P. 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.