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

Adult Male 0301 basic medicine B-Lymphocytes Vaccines, Synthetic 0303 health sciences Hepatitis B Surface Antigens Adolescent T-Lymphocytes Plasmodium falciparum Spores, Protozoan Antibodies, Protozoan 3. Good health 03 medical and health sciences Malaria Vaccines Vaccines, DNA Animals Humans Female Hepatitis B Antibodies Immunization Schedule
DOI: 10.1016/j.vaccine.2004.01.031 Publication Date: 2004-02-13T10:06:52Z
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 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 naïve 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.
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