Vaccine made from mosquito spit could help prevent epidemics
In a new study published this week in The Lancet, NIAID scientists describe the results of a small Phase 1 trial of a vaccine designed to provide broad protection against mosquito-borne diseases. The trial indicated that the vaccine is safe and induces a strong immune response in healthy volunteers.
Unlike other experimental vaccines for mosquito-borne diseases, this experimental vaccine (known as AGS-v) is designed to provoke an immune response against mosquito saliva, rather than any specific parasites, viruses, or bacteria the mosquito might transmit. Ordinarily, when a mosquito bites a person, the natural immune response to the mosquito saliva helps pathogens carried in the saliva to evade the body’s immune response. With this vaccine, the immune system is trained to respond differently to mosquito saliva, and the pathogen is no longer able to hide from activated immune cells. Developed by the London-based pharmaceutical company SEEK via its subsidiary, Imutex Limited, and produced by CordenPharma (based in Liestal, Switzerland and in Caponago, Italy), the vaccine contains four synthetic peptides that can also be found in mosquito salivary gland proteins. The double-blind study, which began in 2017 at the NIH Clinical Center in Bethesda, Maryland,(link is external) was led by NIAID’s Laboratory of Infectious Diseases Clinical Studies unit, in collaboration with the Vector Molecular Biology Section.
The double-blind study was the first trial of this so-called “universal mosquito vaccine” in humans. Forty-nine healthy volunteers enrolled in the study and were randomly assigned to one of three groups. One group received two injections of a placebo (sterile water), one group received two injections of the vaccine, and one group received two injections of a combination of the vaccine and an adjuvant. Addition of the adjuvant generates a water in oil emulsion, which is commonly added to vaccines to enhance immune responses. In all groups, the two subcutaneous injections were given 21 days apart.
On the 42nd day of the study, volunteers underwent a “feeding session” with disease-free mosquitoes, which had been bred in captivity at the NIH. The mosquitoes were placed into a contained feeding device (resembling a cup) and fed briefly from volunteers’ arms through a fine mesh. Volunteers were monitored after each vaccination, after the feeding session, and at regular follow-up visits for twelve months after the first vaccination. The mosquitoes were also monitored after the feeding session, to see whether the vaccine had any impact on their survival and the number of offspring they produced.
None of the volunteers had serious adverse reactions to the vaccine or mosquito feeding, although one volunteer did develop a significant rash after the first dose of the vaccine.
The volunteers’ blood tests showed that the vaccine in combination with the adjuvant produced a significant immune response to mosquito salivary peptides. Further, this immune response was not accompanied by a worse reaction to mosquito bites; volunteers reported only the usual itching and discomfort after their mosquito feeding sessions.
The authors say the study’s results are promising and suggest that further research to test the vaccine’s efficacy against individual pathogens, followed by larger field studies, would be worthwhile. A widely available “universal” vaccine could provide protection against emerging and re-emerging mosquito-borne diseases as they arise, allowing public health officials to quickly respond to new outbreaks and epidemics without waiting for new treatments or vaccines to be developed.
J. Manning, et al. Safety and immunogenicity of a first-in-human mosquito saliva peptide vaccine: a randomized, placebo-controlled, double-blind Phase 1 trial. The Lancet. DOI: 10.1016/S0140-6736(20)31048-5(link is external)pdf (2020)