Experimental Malaria Vaccine Plus Chloroquine Protects Against Controlled Infection, Study Finds

February 15, 2017

An experimental malaria vaccine strategy known as PfSPZ-CVac, together with antimalarial medication, protected all nine clinical trial volunteers given three high-dose vaccinations, according to study results published today in Nature

The study was supported in part by grants and technical assistance from scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The data add to a growing body of scientific evidence showing that vaccines created using live malaria parasites can be safe, well-tolerated, and potentially effective if used in mass vaccination programs to eradicate malaria from geographically defined areas, according to the authors. 

PfSPZ-CVac, developed by Sanaria Inc., of Rockville, Maryland, is administered intravenously to generate an immune response to protect against malaria infection. The vaccine introduces live Plasmodium falciparum malaria parasites into the bloodstream; these parasites are ordinarily transmitted to humans through the bite of an infected mosquito. Oral antimalarial medication (chloroquine) is given simultaneously to prevent an actual malarial infection.

The new study was conducted at the University of Tubingen, Germany. Sixty-seven healthy adult participants were randomly assigned to receive either: three injections at varying dosage levels of PfSPZ-CVac at 28-day intervals; three injections of the highest dosage levels at shorter intervals (5-day or 14-day intervals), or a placebo injection. All recipients were simultaneously given oral doses of chloroquine. Participants then underwent controlled exposure to infectious malaria parasites 10 weeks after the final vaccination.

All nine participants who received three injections of the highest dose of PfSPZ-CVac (5.12x10 4) at 28-day intervals were protected against P. falciparum malaria 10 weeks after their last vaccine dose. Participants who received lower dosages or the highest dose at shorter intervals exhibited less immunity to malaria infection. For example, the highest dosages of vaccine administered three times at 5-day intervals protected 63 percent of participants (5 of 8); the highest vaccine doses administered three times at 14-day intervals protected 67 percent of participants (6 of 9). The authors suggest that in the field, high doses of the PfSPZ-CVac vaccine will likely be needed to protect against malaria infection.

The researchers showed that PfSPZ-CVac induced a response from vaccine recipients’ T cells—white blood cells that activate the rest of the immune system—which was proportional to the dosage of the vaccine. In addition, they determined that patients whose CD4+ T cells produced multiple kinds of signaling molecules to activate the immune system were more likely to be protected. Antigen Discovery Inc., based in Irvine, California, studied the antibody responses of the nine participants who had complete protection and identified 22 malaria parasite proteins that could be the targets of protective immune responses.

Phase 2 trials are planned to test PfSPZ-CVac in the African countries of Mali, Ghana, and Gabon to evaluate the optimal dose and schedule for protection in malaria-endemic areas.

Through Small Business Innovation Research grants, NIAID supported the preclinical development and, in part, the manufacture of the PfSPZ-CVac Vaccine, as well as the antibody response analysis and the identification of the potential protective malaria protein. NIAID also provided cellular immune analysis.

ARTICLE:
B. Mordmüller et al. Sterile protection against human malaria by chemoattenuated PfSPZ vaccine. Nature DOI 10.1038/nature21060 (2017).

WHO:
NIAID Director Anthony S. Fauci, M.D., and Robert A. Seder, M.D., chief of the Cellular Immunology Section of NIAID’s Vaccine Research Center and study co-author, are available for comment.

Content last reviewed on February 15, 2017