A Walter Reed Army Institute of Research, Clinical Trials Center researcher holds a vial of FMP013 Malaria Vaccine during a clinical trial. Credit: Mike Walters/U.S. Army
The COVID-19 pandemic didn’t raise the global mortality rate due to just SARS-CoV-2. Studies have already shown an increase in the U.S. in some cancers and other long-term illnesses as healthcare visits became less frequent when the world shut down.
The pandemic caused similar disruptions in sub-Saharan Africa, where the World Health Organisation (WHO) reported 14 million more cases of malaria in 2020 compared with 2019, resulting in 69,000 more deaths. Approximately two-thirds of these additional deaths—about 47,000—were linked to disruptions in the provision of malaria prevention, diagnosis and treatment during the pandemic.
In October 2021, RTS,S, known by the brand name Mosquirix, became the first malaria vaccine recommended by WHO for large-scale use in children living in areas with moderate-to-high malaria transmission. In sub-Saharan Africa—which accounts for 95% of all malaria cases—80% of deaths are among children under 5 years of age. While impactful and urgently needed, Mosquirix provides only moderate protection that wanes within months.
Thus, many researchers are still working to improve malaria vaccine strategies, including Sheetij Dutta, chief of the Structural Vaccinology Laboratory at Walter Reed Army Institute of Research (WRAIR). For more than three decades U.S. Army researchers have developed malaria vaccine candidates, testing their safety and ability to elicit protective immune responses against infection.
In a new paper featuring results from a Phase 1 clinical trial, Dutta’s creation—the FMP013 vaccine—appears safe and immunogenic for adults in its first-in-human evaluation. The FMP013 vaccine directs the immune system to develop antibodies to the circumsporozoite protein (CSP) of the malaria parasite Plasmodium falciparum—the same protein that is the basis for the RTS,S vaccine. But, Dutta says his team included portions of the CSP protein in this vaccine that were not present in the RTS,S version.
“The vaccine design broadens the host immune response to epitopes that were not included in the RTS,S vaccine and targeting these additional susceptible epitopes on CSP could be the key to an improved vaccine,” explained Dutta.
Another element that makes FMP013 unique is the inclusion of the adjuvant Army Liposome Formulation with QS-21, or ALFQ, which was developed at WRAIR by the Military HIV Research Program. ALFQ stimulates the immune response, making the vaccine as a whole more effective. So effective, in fact, that it is now being tested with vaccines against a number of other infectious diseases including COVID-19, bacterial diarrhea and HIV.
The Phase 1 clinical trail of the FMP013/ALFQ malaria vaccine candidate enrolled 10 volunteers—five of which received a low dose (20 lg FMP013/0.5 mL ALFQ), and five of which received a high dose (40 lg FMP013/1.0 mL ALFQ).
According to the results, published in Vaccine, both groups exhibited robust humoral and cellular immunological responses and compared favorably with historical responses reported for RTS,S/AS01. Additionally, the clinical safety profile was acceptable and there were no serious adverse events.
Ultimately, the low dose version of the vaccine was selected for follow-on efficacy testing via a WRAIR-designed controlled human malaria infection (CHMI) model. In the model, volunteers receive the malaria vaccines, then are bitten by malaria-infected mosquitoes at the WRAIR Entomology Branch. Volunteers who develop parasitemia are then cured very early in the infection with a commonly used malaria drug. These safety and efficacy results are expected to be published by the end of 2022.