Fractional Third and Fourth Dose of RTS,S/AS01 Malaria Candidate Vaccine: A Phase 2a Controlled Human Malaria Parasite Infection and Immunogenicity Study JOURNAL OF INFECTIOUS DISEASES Regules, J. A., Cicatelli, S. B., Bennett, J. W., Paolino, K. M., Twomey, P. S., Moon, J. E., Kathcart, A. K., Hauns, K. D., Komisar, J. L., Qabar, A. N., Davidson, S. A., Dutta, S., Griffith, M. E., Magee, C. D., Wojnarski, M., Livezey, J. R., Kress, A. T., Waterman, P. E., Jongert, E., Wille-Reece, U., Volkmuth, W., Emerling, D., Robinson, W. H., Lievens, M., Morelle, D., Lee, C. K., Yassin-Rajkumar, B., Weltzin, R., Cohen, J., Paris, R. M., Waters, N. C., Birkett, A. J., Kaslow, D. C., Ballou, W. R., Ockenhouse, C. F., Vekemans, J. 2016; 214 (5): 762-771


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.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.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.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.NCT01857869.

View details for DOI 10.1093/infdis/jiw237

View details for Web of Science ID 000385346400015

View details for PubMedID 27296848