title: 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 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.
authors.affiliation: Malaria Program, Naval Medical Research Center, 503 Robert Grant Ave, Silver Spring, MD 20910, USA.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Epstein
authors.forename: Yupin
authors.initials: Y
authors.lastname: Charoenvit
authors.forename: Kent E
authors.initials: KE
authors.lastname: Kester
authors.forename: Ruobing
authors.initials: R
authors.lastname: Wang
authors.forename: Rhonda
authors.initials: R
authors.lastname: Newcomer
authors.forename: Steve
authors.initials: S
authors.lastname: Fitzpatrick
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Richie
authors.forename: Nadia
authors.initials: N
authors.lastname: Tornieporth
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
authors.forename: Chris
authors.initials: C
authors.lastname: Ockenhouse
authors.forename: Victoria
authors.initials: V
authors.lastname: Majam
authors.forename: Carolyn
authors.initials: C
authors.lastname: Holland
authors.forename: Esteban
authors.initials: E
authors.lastname: Abot
authors.forename: Harini
authors.initials: H
authors.lastname: Ganeshan
authors.forename: Mara
authors.initials: M
authors.lastname: Berzins
authors.forename: Trevor
authors.initials: T
authors.lastname: Jones
authors.forename: C Nicole
authors.initials: CN
authors.lastname: Freydberg
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ng
authors.forename: Jon
authors.initials: J
authors.lastname: Norman
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Carucci
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: 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
chemical_list: 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