Safety, tolerability, and antibody responses in humans after sequential immunization with a PfCSP DNA vaccine followed by the recombinant protein vaccine RTS,S/AS02A.
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.
Epstein
Judith E
JE
Malaria Program, Naval Medical Research Center, 503 Robert Grant Ave, Silver Spring, MD 20910, USA.
Charoenvit
Yupin
Y
Kester
Kent E
KE
Wang
Ruobing
R
Newcomer
Rhonda
R
Fitzpatrick
Steve
S
Richie
Thomas L
TL
Tornieporth
Nadia
N
Heppner
D Gray
DG
Ockenhouse
Chris
C
Majam
Victoria
V
Holland
Carolyn
C
Abot
Esteban
E
Ganeshan
Harini
H
Berzins
Mara
M
Jones
Trevor
T
Freydberg
C Nicole
CN
Ng
Jennifer
J
Norman
Jon
J
Carucci
Daniel J
DJ
Cohen
Joe
J
Hoffman
Stephen L
SL
D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000032:analysis / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology*; D033761:Spores, Protozoan / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000009:adverse effects / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology
D000913:Antibodies, Protozoan; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017780:Malaria Vaccines; C487838:PfCSP DNA vaccine; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic