Immunologists Identify How Dosing Strategy Improves Effectiveness of Malaria Vaccine

A team of immunology researchers at the University of Miami Miller School of Medicine has uncovered a mechanism of immune protection for the RTS,S/AS01 malaria vaccine that could lead to an effective malaria vaccination program for children.

“Malaria is one of the world’s deadly infectious diseases, claiming the lives of more than 400,000 children under age 5 worldwide,” said Savita Pahwa, M.D., professor of microbiology and immunology, and director of the Miami Center for AIDS Research (CFAR).  “However, it has been very difficult to develop a vaccine because of the inadequate immune response to the mosquito-borne malaria parasite.”

Several years ago, Phase III clinical testing for RTS,S AS01– a leading malaria vaccine candidate in African infants ­– revealed only 30.1 percent of young participants were protected. A new controlled human malaria infection trial in healthy adults found that changing the dosing strategy, from three equal vaccine doses each given a month apart, to one in which the third dose is reduced to 1/5 and delayed by six months, resulted in significantly higher protection.

A collaborative laboratory study, published April 28 in the journal eLife, found that in both regimens the first two doses increased the ability of the immune system’s B cells to generate antibodies for the disease. However, a third dose at the same amount, given one month after the second dose, could cause the immune system to crash, whereas delaying and reducing the third dose of the RTS,S AS01 vaccine protected the response of the B cells and T peripheral follicular helper (pTfh) cells. “We found this approach was more effective than the standard three-dose regimen,” said Dr. Pahwa. “We hope it will provide long-term, persistent protection against this deadly disease.”

Dr. Pahwa, Suresh Pallikkuth, Ph.D., assistant professor of research, and Li Pan, bioinformatics specialist, were co-authors of the study, “A Delayed Fractionated Dose RTS,S AS01 Vaccine Regimen Mediates Protection Via Improved T Follicular Helper and B Cell Responses.” The work was performed in collaboration with GlaxoSmithKline (GSK) and PATH Malaria Vaccine Initiative, which is supported by the Gates Foundation.  Other study co-authors were from the Biotechnology HPC Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command; the Henry M. Jackson Foundation for the Advancement of Military Medicine; GSK Vaccine, Rixensart, Belgium; and PATH’s Malaria Vaccine Initiative, Washington, D.C.

Dr. Pallikkuth, who was first author of the study, said the Miller School team was asked to conduct immunologic investigations to study the effectiveness of the different vaccine dosing protocols. “We have learned that the delayed third dose regimen appears to be more effective in sustaining the vaccine-induced immune system response,” he said. “We can also use the levels of B and pTfh cells as biomarkers in evaluating individuals’ immune systems.” He added that a field trial is now under way in Africa to test this vaccination strategy.

Dr. Pahwa said the Miller School’s infectious disease program in the Department of Microbiology and Immunology was selected to participate in this anti-malaria initiative based on the team’s leading-edge research on HIV/AIDS and other microbial diseases.

Tags: Dr. Savita Pahwa, Dr. Suresh Pallikkuth, eLIFE, malaria