Two National Institutes of Health (NIH)-supported studies of an experimental malaria vaccine in healthy Malian adults found that all three regimens tested were safe. One of the studies involved 300 healthy women between the ages of 18 and 38 who expected to become pregnant shortly after immunization. That trial began with a drug treatment to remove malaria parasites, followed by three injections over a month of a saline placebo or the study vaccine at one of two doses. Both doses of the vaccine candidate provided a significant level of protection against parasitic infections and clinical malaria, lasting for a period of two years without the need for a booster dose – a first for any malaria vaccine. An exploratory analysis of women who became pregnant during the study found that the vaccine significantly protected them against malaria during pregnancy. If confirmed by additional clinical trials, the approach modeled in this study could open up improved ways to prevent malaria in pregnancy.
Spread by Anopheles mosquitoes, malaria parasites, including those of the species Plasmodium falciparum (Pf), can cause illness in people of any age. However, pregnant women, infants and very young children are particularly vulnerable to life-threatening diseases. Malaria parasitemia during pregnancy is estimated to cause up to 50,000 maternal deaths and 200,000 stillbirths in Africa annually.
The studies were co-led by researchers from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and the University of Sciences, Techniques and Technologies, Bamako (USTTB), Mali. The investigational vaccine used in both studies was the PfSPZ vaccine, a radiation-attenuated vaccine based on Pf sporozoites (a stage in the parasite’s life cycle), manufactured by Sanaria Inc., Rockville, Maryland. Several previous clinical trials of the PfSPZ vaccine have shown it to be safe, including in malaria-endemic countries such as Mali. For example, in results published in 2022, an NIAID-sponsored, placebo-controlled trial of a three-dose PfSPZ vaccine regimen in Burkina Faso showed that the vaccine had up to 46% efficacy and lasted at least 18 months.
In the first year of the current trial, 55 women became pregnant within 24 weeks of the third vaccine dose. Among these women, vaccine efficacy against parasitemia (before or during pregnancy) was 65% in those who received the lower dose vaccine and 86% in those who received the higher dose. Among the 155 women who became pregnant in both study years, vaccine efficacy was 57% for those who received a lower dose of vaccine and 49% for those in the higher dose group.
Women who received the study vaccine at either dose were more likely than those who received placebo, the researchers reported, although this finding did not reach the level of statistical significance. The researchers speculate that the PfSPZ vaccine could prevent malaria-related early pregnancy loss by reducing the risk of parasitemia during the periconception period by 65 to 86%.
“Preconception immunization is a novel strategy to reduce mortality among women with malaria during pregnancy,” the researchers note. They plan to investigate the safety of the PfSPZ vaccine administered during pregnancy and then investigate the efficacy of the PfSPZ vaccine given preconception or during pregnancy in larger clinical trials. “Existing measures do not protect women against malaria during pregnancy,” she added. “A safe and effective vaccine is urgently needed, and our results indicate that the PfSPZ vaccine may be a suitable candidate,” they conclude.
The PfSPZ vaccine study team was led by Alassane Dicko, MD, of the Malaria Research and Training Center (MRTC), USTTB, Mali, Stephen L. Hoffman, MD, of Sanaria Inc., and Patrick E. Duffy, MD, of NIAID Laboratory for Malaria Immunology and Vaccinology. The joint co-first authors were Halimatou Diawara, MD, of MRTC, and Sara A. Healy, MD, NIAID.
