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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.


ABSTRACT: 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.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-? 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-? 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.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.

SUBMITTER: Tamminga C 

PROVIDER: S-EPMC3906401 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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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.

Tamminga Cindy C   Sedegah Martha M   Maiolatesi Santina S   Fedders Charlotte C   Reyes Sharina S   Reyes Anatalio A   Vasquez Carlos C   Alcorta Yolanda Y   Chuang Ilin I   Spring Michele M   Kavanaugh Michael M   Ganeshan Harini H   Huang Jun J   Belmonte Maria M   Abot Esteban E   Belmonte Arnel A   Banania Joglenna J   Farooq Fouzia F   Murphy Jittawadee J   Komisar Jack J   Richie Nancy O NO   Bennett Jason J   Limbach Keith K   Patterson Noelle B NB   Bruder Joseph T JT   Shi Meng M   Miller Edward E   Dutta Sheetij S   Diggs Carter C   Soisson Lorraine A LA   Hollingdale Michael R MR   Epstein Judith E JE   Richie Thomas L TL  

Human vaccines & immunotherapeutics 20130604 10


<h4>Background</h4>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.<h4>Methodology/principal findings</h4>The regimen was a single intramus  ...[more]

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