DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity
- Chuang, I.
- Sedegah, M.
- Cicatelli, S.
- Spring, M.
- Polhemus, M.
- Tamminga, C.
- Patterson, N.
- Guerrero, M.
- Bennett, J.W.
- McGrath, S.
- Ganeshan, H.
- Belmonte, M.
- Farooq, F.
- Abot, E.
- Banania, J.G.
- Huang, J.
- Newcomer, R.
- Rein, L.
- Litilit, D.
- Richie, N.O.
- Wood, C.
- Murphy, J.
- Sauerwein, R.W.
- Hermsen, C.C.
- McCoy, A.J.
- Kamau, E.
- Cummings, J.
- Komisar, J.
- Sutamihardja, A.
- Shi, M.
- Epstein, J.E.
- Maiolatesi, S.
- Tosh, D.
- Limbach, K.
- Angov, E.
- Bergmann-Leitner, E.
- Bruder, J.T.
- Doolan, D.L.
- King, C.R.
- Carucci, D.
- Dutta, S.
- Soisson, L.
- Diggs, C.
- Hollingdale, M.R.
- Ockenhouse, C.F.
- Richie, T.L.
DOIAbstract
BACKGROUND: Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection. METHODOLOGY/PRINCIPAL FINDINGS: The vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at...
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