Vaccine tested for malaria and other mosquito-borne diseases

A research group that includes scientists from the Frederick National Laboratory for Cancer Research has shown that an experimental vaccine designed to simultaneously protect against malaria, Zika, and a host of other mosquito-borne diseases safely provokes a strong immune response when tested in human volunteers. The next step will be to see if the vaccine blocks infection in regions where mosquito-borne diseases are common. 

The Phase 1 clinical trial tested a vaccine that targets mosquito salivary proteins at the bite site. The aim is to stop any mosquito-borne viruses from entering the human bloodstream.  

“Given the high rates of morbidity and mortality of mosquito-borne disease worldwide and the lack of effective prophylactic treatment for most arboviral infections, these first results of human testing hold promise for clinical efficacy, potentially saving many lives,” the research group reported in November in eBioMedicine.  

Matthew Laurens of the University of Maryland School of Medicine and Matthew Memoli of the National Institute of Allergy and Infectious Diseases led the group, which included Allyson Mateja of Frederick National Laboratory’s Clinical Monitoring Research Program. 

The randomized, double-blind, placebo trial enrolled 51 volunteers from Baltimore, Md., between August 2019 and February 2020. Of those volunteers, 15 were unable to attend in-person visits after the 22nd day of the trial because COVID-19 restrictions made it difficult for volunteers to attend all of the on-site study visits. Some safety assessments were done virtually.  

Although the pandemic interfered with the study, “We did document statistically significant immunological differences between vaccine recipients and placebo,” the scientists reported. 

The volunteers were divided into random groups and given various dosing and formulation regimens of a mosquito salivary peptide vaccine, AGS-v PLUS, or a placebo. They were tested for antibody and cytokine levels at days 1, 43, and 50 and exposed to biting mosquitos on day 43. The only reaction to the vaccine that was more common in the vaccine groups compared to placebo was discomfort at the injection site. Compared to the placebo group, all other groups generated robust immune responses to the vaccine, regardless of dosing and formulation. 

Each year, mosquito-borne diseases infect more than 360 million people and claim more than 600,000 lives worldwide. Malaria is the most common and deadly. A recent vaccine for malaria (RTS,S) is effective, but it can difficult to give to people in remote parts of the world where health care access may be limited. The vaccine requires three shots given monthly, followed by a booster after another 18 months.  

Other mosquito-borne diseases, such as the Zika virus which caused an epidemic from 2015-2016, can also pose potentially serious health threats. Zika symptoms are usually mild. But infection during pregnancy can cause serious birth defects. In rare cases, it can lead to other conditions, such as Guillain-Barré syndrome, which often requires hospitalization for treatment. 

The standard public health strategies to prevent mosquito-borne illnesses are insect population control and treating disease symptoms, where possible. But they cannot stop the spread of disease entirely, and healthcare providers need better tools to help those who suffer the most from these maladies. The number of cases and deaths from malaria, for instance, have changed little in recent years. So, a vaccine such as AGS-v PLUS could have a substantial public health benefit, the scientists concluded.