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

Hum Vaccin Immunother. 2013 Oct;9(10):2165-77. doi: 10.4161/hv.24941. Epub 2013 Jun 4.


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. Identifier: NCT00392015.

Trial registration: NCT00392015 NCT00870987.

Keywords: T cells; adenovirus; antibody; efficacy; malaria; vaccine.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenoviruses, Human / genetics*
  • Adolescent
  • Adult
  • Antibodies, Protozoan / blood
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Enzyme-Linked Immunospot Assay
  • Female
  • Genetic Vectors*
  • Humans
  • Injections, Intramuscular
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / immunology
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / adverse effects
  • Malaria Vaccines / genetics
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / prevention & control*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Middle Aged
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Young Adult


  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Malaria Vaccines
  • Membrane Proteins
  • Protozoan Proteins
  • Vaccines, Synthetic
  • apical membrane antigen I, Plasmodium
  • circumsporozoite protein, Protozoan
  • Interferon-gamma

Associated data