First-in-human assessment of safety and immunogenicity of low and high doses of Plasmodium falciparum malaria protein 013 (FMP013) administered intramuscularly with ALFQ adjuvant in healthy malaria-naïve adults.

The global burden of malaria remains substantial. Circumsporozoite protein (CSP) has been demonstrated to be an effective target antigen, however, improvements that offer more efficacious and more durable protection are still needed. In support of research and development of next-generation malaria vaccines, Walter Reed Army Institute of Research (WRAIR) has developed a CSP-based antigen (FMP013) and a novel adjuvant ALFQ (Army Liposome Formulation containing QS-21). We present a single center, open-label, dose-escalation Phase 1 clinical trial to evaluate the safety and immunogenicity of the FMP013/ALFQ malaria vaccine candidate. In this first-in-human evaluation of both the antigen and adjuvant, we enrolled ten subjects; five received 20 μg FMP013 / 0.5 mL ALFQ (Low dose group), and five received 40 μg FMP013 / 1.0 mL ALFQ (High dose group) on study days 1, 29, and 57. Adverse events and immune responses were assessed during the study period. The clinical safety profile was acceptable and there were no serious adverse events. Both groups exhibited robust humoral and cellular immunological responses, and compared favorably with historical responses reported for RTS,S/AS01. Based on a lower reactogenicity profile, the 20 μg FMP013 / 0.5 mL ALFQ (Low dose) was selected for follow-on efficacy testing by controlled human malaria infection (CHMI) with a separate cohort. Trial Registration:Clinicaltrials.gov Identifier NCT04268420 (Registered February 13, 2020).
Competing Interests: Declaration of Competing Interest The authors JNH, LS, KM, VN, PR, EA, DEL, JEM, NCW, MH, HG, CL, LZ, XQ, DRB, ED, JB, XZ, EB, JR declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.  The authors SD, ZB, and GM  declare the following financial interests which may be considered as potential competing interests: SD holds a patent on the FMP013 antigen; SD, ZB, GM have filed a patent for the FMP013/ALFQ formulation. The material has been reviewed by the Walter Reed Army Institute of Research and the US Agency for International Development.  There is no objection to its presentation and/or publication.  The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army, the Department of Defense, or the US Agency for International Development.
(Published by Elsevier Ltd.)