Human adenovirus 5-vectored Plasmodium falciparum NMRC-M3V-Ad-PfCA vaccine encoding CSP and AMA1 is safe, well-tolerated and immunogenic but does not protect against controlled human malaria infection.

Autor:	Tamminga C; Naval Medical Research Center; Silver Spring, MD USA., Sedegah M; Naval Medical Research Center; Silver Spring, MD USA., Maiolatesi S; Naval Medical Research Center; Silver Spring, MD USA., Fedders C; Naval Medical Research Center; Silver Spring, MD USA., Reyes S; Naval Medical Research Center; Silver Spring, MD USA., Reyes A; Naval Medical Research Center; Silver Spring, MD USA., Vasquez C; Naval Medical Research Center; Silver Spring, MD USA., Alcorta Y; Naval Medical Research Center; Silver Spring, MD USA., Chuang I; Naval Medical Research Center; Silver Spring, MD USA., Spring M; Armed Forces Research Institute of Medical Sciences; Bangkok, Thailand., Kavanaugh M; National Naval Medical Center; Bethesda, MD USA., Ganeshan H; Naval Medical Research Center; Silver Spring, MD USA., Huang J; Naval Medical Research Center; Silver Spring, MD USA., Belmonte M; Naval Medical Research Center; Silver Spring, MD USA., Abot E; Naval Medical Research Center; Silver Spring, MD USA., Belmonte A; Naval Medical Research Center; Silver Spring, MD USA., Banania J; Naval Medical Research Center; Silver Spring, MD USA., Farooq F; Naval Medical Research Center; Silver Spring, MD USA., Murphy J; Walter Reed Army Institute of Research; Silver Spring, MD USA., Komisar J; Walter Reed Army Institute of Research; Silver Spring, MD USA., Richie NO; Walter Reed Army Institute of Research; Silver Spring, MD USA., Bennett J; Walter Reed Army Institute of Research; Silver Spring, MD USA., Limbach K; Naval Medical Research Center; Silver Spring, MD USA., Patterson NB; Naval Medical Research Center; Silver Spring, MD USA., Bruder JT; GenVec Inc.; Gaithersburg, MD USA., Shi M; Walter Reed Army Institute of Research; Silver Spring, MD USA., Miller E; National Naval Medical Center; Bethesda, MD USA., Dutta S; Walter Reed Army Institute of Research; Silver Spring, MD USA., Diggs C; USAID; Washington, DC USA., Soisson LA; USAID; Washington, DC USA., Hollingdale MR; Naval Medical Research Center; Silver Spring, MD USA., Epstein JE; Naval Medical Research Center; Silver Spring, MD USA., Richie TL; Naval Medical Research Center; Silver Spring, MD USA.
Jazyk:	angličtina
Zdroj:	Human vaccines & immunotherapeutics [Hum Vaccin Immunother] 2013 Oct; Vol. 9 (10), pp. 2165-77. Date of Electronic Publication: 2013 Jun 04.
DOI:	10.4161/hv.24941
Abstrakt:	Background: In a prior study, a DNA prime / adenovirus boost vaccine (DNA/Ad) expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1) (NMRC-M3V-D/Ad-PfCA Vaccine) induced 27% protection against controlled human malaria infection (CHMI). To investigate the contribution of DNA priming, we tested the efficacy of adenovirus vaccine alone (NMRC-M3V-Ad-PfCA ) in a Phase 1 clinical trial. Methodology/principal Findings: The regimen was a single intramuscular injection with two non-replicating human serotype 5 adenovectors encoding CSP and AMA1, respectively. One x 10 (10) particle units of each construct were combined prior to administration. The regimen was safe and well-tolerated. Four weeks later, 18 study subjects received P. falciparum CHMI administered by mosquito bite. None were fully protected although one showed delayed onset of parasitemia. Antibody responses were low, with geometric mean CSP ELISA titer of 381 (range<50-1626) and AMA1 ELISA of 4.95 µg/mL (range 0.2-38). Summed ex vivo IFN-γ ELISpot responses to overlapping peptides were robust, with geometric mean spot forming cells/million peripheral blood mononuclear cells [sfc/m] for CSP of 273 (range 38-2550) and for AMA1 of 1303 (range 435-4594). CD4+ and CD8+ T cell IFN-γ responses to CSP were positive by flow cytometry in 25% and 56% of the research subjects, respectively, and to AMA1 in 94% and 100%, respectively. Significance: In contrast to DNA/Ad, Ad alone did not protect against CHMI despite inducing broad, cell-mediated immunity, indicating that DNA priming is required for protection by the adenovirus-vectored vaccine. ClinicalTrials.gov Identifier: NCT00392015.
Databáze:	MEDLINE
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