A new malaria vaccine showed encouraging results in a phase 1 study conducted in Bamako, Mali, West Africa, a region where malaria remains a year-round threat to public health.

Published in NEJM Evidence, this study evaluated a vaccine designed to block malaria transmission by targeting the Pfs230D1 protein, a molecule expressed later in the parasite’s life cycle.

Sara A. Healy, MD, MPH, consulting clinical investigator at the Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, led the trial in three villages near Bamako.

She and her colleagues investigated whether the vaccine could prevent Plasmodium falciparum from passing from humans to mosquitoes, which is a critical step in interrupting the epidemic chain.

Study Findings

The trial findings highlight the promise of transmission-blocking vaccines as a complement to existing malaria-control strategies, including mosquito control, artemisinin-based therapy, and insecticide-treated mosquito nets.

Vaccination campaigns have gained increasing importance since 2022, with two malaria vaccines — RTS,S and R21 — being deployed across sub-Saharan Africa.

Both the R21 and RTS,S vaccines target the circumsporozoite protein, a key surface protein on Plasmodium sporozoites, thereby preventing the parasite from entering the liver. These vaccines are only indicated for children.

Unlike existing vaccines, the Pfs230D1 vaccine is designed to halt transmission from infected humans to mosquitoes.

In a phase 1 study, the vaccine was well tolerated, with mostly mild-to-moderate side effects, such as pain at the injection site, fever, and headaches.

Two dosing regimens were tested: a high-dose schedule of four doses (40 µg each at 0, 1, 6, and 18 months) and a split-dose schedule with a reduced third dose. Both induced robust immune responses, predominantly with immunoglobulin G1 antibodies.

Researchers first used a standard membrane-feeding assay, exposing mosquitoes to parasites incubated with serum from vaccinated participants. The serum exhibited inhibitory activity that correlated with antibody levels.

In a second experiment, direct skin-feeding, mosquitoes fed directly on participants, some of whom contracted malaria because of the high prevalence of the disease in the region during the study.

At the primary endpoint, 6 weeks after the third dose, the transmission reduction was not significant.

However, the fourth dose proved transformative, and in the second year, it was associated with a 90.6% reduction in human-to-mosquito transmission of P falciparum.

According to the researchers, modelling studies suggest that mass administration of a combined vaccine targeting both the circumsporozoite protein and transmission-blocking antigens would have a greater impact than either vaccine alone. This combined strategy reduces parasite transmission through herd immunity, enabling disease control in areas with high transmission rates and facilitating its elimination in areas with low transmission rates.

Challenges

After decades of progress, malaria cases are increasing again, driven by emerging resistance to parasites and mosquitoes, climate change, and potential reductions in global funds.

The US Agency for International Development, headquartered in Washington, DC, is the world’s leading financier in the fight against three major pandemics: HIV/AIDS, tuberculosis, and malaria.

These findings highlight a promising new strategy in the ongoing fight against malaria: Pairing transmission-blocking vaccines with existing interventions may provide a powerful tool for reducing the global burden of this persistent disease.

This story was translated from MediQuality.