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.
Publication/Presentation Date
10-1-2013
Abstract
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
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.
Volume
9
Issue
10
First Page
2165
Last Page
2177
ISSN
2164-554X
Published In/Presented At
Tamminga, C., Sedegah, M., Maiolatesi, S., Fedders, C., Reyes, S., Reyes, A., Vasquez, C., Alcorta, Y., Chuang, I., Spring, M., Kavanaugh, M., Ganeshan, H., Huang, J., Belmonte, M., Abot, E., Belmonte, A., Banania, J., Farooq, F., Murphy, J., Komisar, J., … Richie, T. L. (2013). 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. Human vaccines & immunotherapeutics, 9(10), 2165–2177. https://doi.org/10.4161/hv.24941
Disciplines
Medicine and Health Sciences
PubMedID
23899517
Department(s)
Department of Medicine
Document Type
Article