Secreted HSP Vaccine for Malaria Prophylaxis

U.S. military forces are at great risk of developing malaria while deployed in endemic areas. In fact, more person-days were lost among U.S. military personnel due to malaria than to bullets during every military campaign fought in malaria-endemic regions during the 20th century. Malaria also is a major threat to non-military travelers, who face this infection as likely the single greatest health risk associated with travel. Increasing drug and insecticide resistance highlight the importance of developing an effective malaria vaccine. Vaccine efforts to control Plasmodium causing malaria have only been partly successful with 50.4% protection by the RTS,S/AS01E vaccine targeting the circumsporozoite protein (CSP). A major shortcoming of this vaccine approach is a failure to induce high frequencies of cytotoxic T cells that can eliminate malaria at the liver stage of infection.

We have previously shown that cell-based vaccines secreting heat shock protein gp96 are safe for use in humans and represent the most efficient vaccine approach studied to date for stimulating cytotoxic T cells. In the proposed studies, we will adapt this vaccine approach to stimulate cytotoxic T cells against malaria antigens and investigate the optimal vaccination route to target these T cells to the liver.

To accomplish these studies, we will collaborate with experts in the malaria vaccine field, Capt. Thomas L. Richie, M.D., Ph.D., director of the Navy’s malaria research program at the Naval Medical Research Center and coordinator of the U.S. Military Malaria Vaccine Program. Capt. Richie has extensive research experience in human and non-human primate malaria prophylaxis studies, most recently in testing efficacy of adenovirus 5 (Ad5)-vectored Plasmodium falciparum malaria vaccines. Due to this experience, the appropriate personnel, equipment, facilities, and protocols to conduct immunogenicity studies of gp96-Ig-based malaria vaccines are already in place.

The project will be organized such that the expertise of Dr. Podack in generating new cell-based gp96-Ig vaccines is utilized during the first two aims of the grant to generate a candidate malaria vaccine and determine its immunogenicity in mouse models. In aim 3, the vaccines generated by Dr. Podack will be transferred to Capt. Richie for coordination of the non-human primate immunogenicity studies. This collaboration strategy optimizes the individual expertise of both PIs on the grant. Importantly, the NHP immunogenicity studies will be conducted at the facilities and using protocols previously used for testing of recent clinical candidates for malaria prophylaxis.

By conducting head-to-head studies to another promising malaria vaccine, these studies will help to set clinical priorities based on the most effective pre-clinical data in animal models.

Immunology
Vaccines

Sep 2013 — Sep 2016

$986,000