Last Updated: 28/12/2025
GMP Production and Clinical Trial of a Self-Assembling Protein Nanoparticle and Toll-Like Receptor Liposomal MPL Adjuvanted Malaria Vaccine
Objectives
The objective of the study is to conduct a human Phase 1/2a clinical trial of a nanoparticle malaria vaccine formulated in a liposome-based adjuvant. Following vaccination, the volunteers will undergo a controlled human malaria infection (CHMI) by being subjected to bites of five mosquitoes infected with a chloroquine-sensitive stain of Plasmodium falciparum.
The specific aim of the study is to provide evidence to support the hypothesis that a Self-Assembling Protein Nanoparticle (SAPN) designed using the tenets inherent in modern structural and molecular biology, when formulated in a synthetic MPLA liposomal adjuvant, will be superior to the current malaria vaccine RTS,S.
Walter Reed Army Institute of Research (WRAIR), United States
One of the Priority Research Areas for the Fiscal Year 2014 Joint Warfighter Medical Research Program is the Military Infectious Disease Research Program focus on vaccines for malaria. This proposal outlines the steps needed to secure both the protein and adjuvant components of the vaccine. These two components will be combined to form the vaccine FMP-014 to be used in a human clinical trial.
The protein component of the vaccine, PfCSP-TSR-SAPN, will be produce, purified, and vialed using Good Manufacturing Practice guidelines at Walter Reed Army Institute of Research (WRAIR). The adjuvant, L(MPLA), will be manufactured by Avanti Polar Lipids and shipped to WRAIR for sterile vialing. After passing identity, sterility, stability, and toxicology studies, the products will undergo animal safety and immunogenicity testing in mice and rhesus monkeys. The PfCSP-TSR-SAPN and L(MPLA) adjuvant will be combined to form vaccine FMP-014 just before immunization by intramuscular injection.
For the clinical trial, three groups of human volunteers will be recruited. Dosage Schedule #1(DS#1), 15 individuals, will receive three doses of vaccine (25, 25, 5 ug) at 0, 4, 12 weeks, respectively; Dosage Schedule #2 (DS#2), 15 individuals, will receive three doses of vaccine (25, 25, 5 ug) at 0, 4, 26 weeks, respectively; and Group #3 (6 individuals) will not receive any vaccine and will serve as infectivity controls. All groups will undergo CHMI on the same day. They will be monitored for 25 days to detect any blood stage parasites, which will indicate failure of the vaccine to induce a protective immune response against the sporozoite stage of the parasite that was injected by the mosquito.
America Service members and diplomats are stationed all over the world including many areas where malaria is endemic. In our malaria-naïve military population, malaria infection can severely degrade performance, result in missed duty, may require prolonged hospitalization, and, in some cases, result in death. Recent events in a number of endemic locations including Liberia in 2003 and 2009-2010, Benin in 2009, and Haiti in 2010, underscore the Department of Defense’s critical need for a malaria vaccine for deployed military personnel. If the FMP-014 Vaccine, can, as planned, be used to eliminate and eradicate malaria this would have a significant impact on the health of U.S. military personnel.
Jul 2015 — Dec 2022
$2.39M
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