U.S. Department of Defense

 

Authors

Kent E. Kester, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
James F. Cummings, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
Christian F. Ockenhouse, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
Robin Nielsen, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
B. Ted Hall, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
Daniel M. Gordon, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
Robert J. Schwenk, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
Urszula Krzych, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
Carolyn A. Holland, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
Gregory Richmond, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
Megan G. Dowler, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
Jackie Williams, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
Robert A. Wirtz, Centers for Disease Control & Prevention, Atlanta, GA, USA
Nadia Tornieporth, GlaxoSmithKline Biologicals, Rixensart, Belgium
Laurence Vigneron, GlaxoSmithKline Biologicals, Rixensart, Belgium
Martine Delchambre, GlaxoSmithKline Biologicals, Rixensart, Belgium
Marie-Ange Demoitie, GlaxoSmithKline Biologicals, Rixensart, Belgium
W. Ripley Ballou, GlaxoSmithKline Biologicals, Rixensart, Belgium
Joe Cohen, GlaxoSmithKline Biologicals, Rixensart, Belgium
D. Gray Heppner Jr., Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA

Date of this Version

2008

Comments

Published in Vaccine (2008) 26, 2191—2202.

Abstract

Background: Immunization with RTS,S/AS02 consistently protects some vaccinees against malaria infection in experimental challenges and in field trials. A brief immunization schedule against falciparum malaria would be compatible with the Expanded Programme on Immunization, or in combination with other prevention measures, interrupt epidemic malaria or protect individuals upon sudden travel to an endemic area.
Methods: We conducted an open label, Phase 2a trial of two different full dose schedules of RTS,S/AS02 in 40 healthy malaria-naıve adults. Cohort 1 (n = 20) was immunized on a 0, 1, and 3 month schedule and Cohort 2 (n = 20) on a 0, 7, and 28 day schedule. Three weeks later, 38 vaccinees and 12 unimmunized infectivity controls underwent malaria challenge.
Results: Both regimens had a good safety and tolerability profile. Peak GMCs of antibody to the circumsporozoite protein (CSP) were similar in Cohort 1 (78 μg/mL; 95% CI: 45—134) and Cohort 2 (65 μg/mL; 95% CI: 40—104). Vaccine efficacy for Cohort 1 was 45% (95% CI: 18—62%) and for Cohort 2, 39% (95% CI: 11—56%). Protected volunteers had a higher GMC of anti-CSP antibody (114 μg/mL) than did volunteers with a 2-day delay (70 μg/mL) or no delay (30 μg/mL) in the time to onset of parasitemia (Kruskal—Wallis, p = 0.019). A trend was seen for higher CSP-specific IFN-γ responses in PBMC from protected volunteers only in Cohort 1, but not in Cohort 2, for ex vivo and for cultured ELISPOT assays.
Conclusion: In malaria-naıve adults, the efficacy of three-dose RTS,S/AS02 regimens on either a 0, 1, and 3 month schedule or an abbreviated 0, 7, and 28 day schedule was not discernibly different from two previously reported trials of two-dose regimens given at 0, 1 month that conferred 47% (95% CI: −19 to 76%) protection and in another trial 42% (95% CI: 5—63%). A strong association of CSP-specific antibody with protection against malaria challenge is observed and confirms similar observations made in other studies. Subsequent trials of adjuvanted RTS,S in African children and infants on a 0, 1, and 2 month schedule have demonstrated a favorable safety and efficacy profile.

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