Protection Induced by a Novel Circumsporozoite Protein Malaria Vaccine is Associated with the Quality of Antibody Responses
Paul M Robben, Jack N Hutter, Lei Zhu, Heather Galli, Michael A Koren, James E Moon, Dallas R Brown, Tanisha M Robinson, Elizabeth H Duncan, Arnel D Belmonte, Martha Sedegah, Ines Lakhal-Naouar, Sheila Peel, Jessica S Bolton, Wathsala Wijayalath, Lorraine Soisson, Mangala Rao, Gary R Matyas, Evelina Angov, Elke S Bergmann-Leitner, Jason A Regules, Sheetij DuttaAbstract
Background
Malaria remains an intractable global health problem. We report results of a single-center, open-label Phase 1 trial of a nearly full-length soluble recombinant Plasmodium falciparum CSP (FMP013) formulated in the Army Liposome Formulation containing QS21 (ALFQ).
Methods
Healthy malaria-naïve adults (n=29) were enrolled into three groups. Standard (STD) group volunteers received FMP013/AFLQ (20 µg/0.5 mL) on a 0-1-2-month schedule (n=10). Delayed group (DEL) received the same dose on a 0-1-6-month schedule (n=10). Delayed Fractional Dose (DFD) volunteers (n=9), vaccinated at 0-1-6-months, received a fractional third dose (4 µg/0.1 mL). Immunized and unvaccinated control participants underwent P. falciparum-infected mosquito bite challenge three weeks after the third immunization and safety, tolerability, efficacy, and immunogenicity were analyzed.
Results
All regimens were well tolerated. 5 of 9 DEL (vaccine efficacy [VE], 55.6%, 95% confidence interval [CI], 21.2-86.3%; P< 0.001), 1 of 7 DFD (VE 14.3%, CI 0.0-57.9%), and 1 of 9 STD (VE 11.1%, CI 0.0-48.3%) subjects had sterile protection. Delayed blood-stage infection was observed in 3 DEL, 2 DFD and 1 STD subjects. The FMP013/ALFQ vaccine elicited C-terminal biased responses and protection in the DEL regimen was associated with higher C-terminal avidity, and junction, minor repeat epitope-specific responses.
Conclusions
A soluble protein CSP vaccine, akin to particle vaccines, can elicit a protective response when delivered using a potent adjuvant and an extended vaccination schedule. These data encourage further evaluation of FMP013/ALFQ efficacy and durability in the field.