When mosquitoes bite they inject a tiny amount of their saliva, which is a mixture of molecules with various biological activities. Some of these molecules are immunogenic, meaning that they determine a response by the immune system. Previous studies showed that vaccinating animals with mosquito salivary molecules can reduce the risk of infection and the pathology caused by vector-borne pathogens. A paper (1) published last month in The Lancet showed that injecting people with mosquito saliva molecules is safe and may provide a platform for vaccine development.
What is the rationale behind a mosquito saliva vaccine?
In general terms, vaccination is basically a way of artificially “preparing” the immune system to fight infection using dead pathogens or directly their molecules. However, the immune system also reacts to peptides contained in insect saliva. Interestingly, some of these molecules also facilitate invasion and survival of vector-borne pathogens. This has been observed in mosquito arboviruses and parasites transmitted by tsetse and sand flies. So it is reasonable to think that if we can prepare the immune system against these salivary compounds, we can also affect the pathogens at the site of the bite. Indeed, a few animal studies in the past showed that injecting peptides from vector saliva reduces both pathogen numbers and disease severity when animals are challenged with the parasites themselves.
What does the study published in The Lancet show exactly?
In the study, a vaccine cocktail containing four synthetic salivary peptides from the mosquito Anopheles gambiae (the major african malaria vector) was administered to healthy volunteers. Researchers then looked at two outcomes: the occurrence of adverse reactions and the characteristics of the induced immune response. The results showed that the cocktail is indeed immunogenic (sparking the development of IgG antibodies and interferon gamma), while the occurrence of adverse reactions was minimal and limited to the site of the injection.
A promising yet long way ahead
As pointed out in a commentary to the paper (2), the results are promising in the sense that they suggest that using mosquito saliva peptides is fundamentally safe. We don’t have effective vaccines against most vector-borne pathogens, with the exception of yellow fever and japanese encephalitis viruses, and those available only protect against their specific target. Hence, vector saliva could potentially act as a broad-spectrum vaccine against several pathogens transmitted by the same insect. However, the fundamental question that still needs to be answered is: do these salivary molecules really protect against infection? Animal studies suggest they should, but their action must be proven in humans as well.
In conclusion, mosquito saliva could provide in the future an alternative to the development of more traditional vaccines targeting the pathogens themselves.
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- Manning JE, Oliveira F, Coutinho-Abreu IV, et al. Safety and immunogenicity of a mosquito saliva peptide-based vaccine: a randomised, placebo-controlled, double-blind, phase 1 trial. Lancet. 2020;395(10242):1998-2007. doi:10.1016/S0140-6736(20)31048-5
- Nuttall P. Vaccinating against mosquitoes: anticipating the unexpected. Lancet. 2020;395(10242):1953-1954. doi:10.1016/S0140-6736(20)31319-2
A very interesting approach for vaccine development. Maybe, in the future it could be also applied for African and American trypanosomiasis. At least, promising results were found after rhesus macaque immunisation using this approach against cutaneous leishmaniasis.
Indeed! We have to wait and see, hoping human studies will confirm it