We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Fractional Third and Fourth Dose of RTS,S/AS01 Malaria Candidate Vaccine: A Phase 2a Controlled Human Malaria Parasite Infection and Immunogenicity Study.
- Authors
Regules, Jason A.; Cicatelli, Susan B.; Bennett, Jason W.; Paolino, Kristopher M.; Twomey, Patrick S.; Moon, James E.; Kathcart, April K.; Hauns, Kevin D.; Komisar, Jack L.; Qabar, Aziz N.; Davidson, Silas A.; Dutta, Sheetij; Griffith, Matthew E.; Magee, Charles D.; Wojnarski, Mariusz; Livezey, Jeffrey R.; Kress, Adrian T.; Waterman, Paige E.; Jongert, Erik; Wille-Reece, Ulrike
- Abstract
<bold>Background: </bold>Three full doses of RTS,S/AS01 malaria vaccine provides partial protection against controlled human malaria parasite infection (CHMI) and natural exposure. Immunization regimens, including a delayed fractional third dose, were assessed for potential increased protection against malaria and immunologic responses.<bold>Methods: </bold>In a phase 2a, controlled, open-label, study of healthy malaria-naive adults, 16 subjects vaccinated with a 0-, 1-, and 2-month full-dose regimen (012M) and 30 subjects who received a 0-, 1-, and 7-month regimen, including a fractional third dose (Fx017M), underwent CHMI 3 weeks after the last dose. Plasmablast heavy and light chain immunoglobulin messenger RNA sequencing and antibody avidity were evaluated. Protection against repeat CHMI was evaluated after 8 months.<bold>Results: </bold>A total of 26 of 30 subjects in the Fx017M group (vaccine efficacy [VE], 86.7% [95% confidence interval [CI], 66.8%-94.6%]; P < .0001) and 10 of 16 in the 012M group (VE, 62.5% [95% CI, 29.4%-80.1%]; P = .0009) were protected against infection, and protection differed between schedules (P = .040, by the log rank test). The fractional dose boosting increased antibody somatic hypermutation and avidity and sustained high protection upon rechallenge.<bold>Discussions: </bold>A delayed third fractional vaccine dose improved immunogenicity and protection against infection. Optimization of the RTS,S/AS01 immunization regimen may lead to improved approaches against malaria.<bold>Clinical Trials Registration: </bold>NCT01857869.
- Subjects
MALARIA; IMMUNIZATION; IMMUNE response; IMMUNOGLOBULINS; RNA sequencing; CONFIDENCE intervals; VACCINATION
- Publication
Journal of Infectious Diseases, 2016, Vol 214, Issue 5, p762
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiw237