Vector microbiota manipulation by host antibodies: the forgotten strategy to develop transmission-blocking vaccines

Abstract

Human and animal pathogens that are transmitted by arthropods are a global concern, particularly those vectored by ticks (e.g. Borrelia burgdorferi and tick-borne encephalitis virus) and mosquitoes (e.g. malaria and dengue virus). Breaking the circulation of pathogens in permanent foci by controlling vectors using acaricide-based approaches is threatened by the selection of acaricide resistance in vector populations, poor management practices and relaxing of control measures. Alternative strategies that can reduce vector populations and/or vector-mediated transmission are encouraged worldwide. In recent years, it has become clear that arthropod-associated microbiota are involved in many aspects of host physiology and vector competence, prompting research into vector microbiota manipulation. Here, we review how increased knowledge of microbial ecology and vector-host interactions is driving the emergence of new concepts and tools for vector and pathogen control. We focus on the immune functions of host antibodies taken in the blood meal as they can target pathogens and microbiota bacteria within hematophagous arthropods. Anti-microbiota vaccines are presented as a tool to manipulate the vector microbiota and interfere with the development of pathogens within their vectors. Since the importance of some bacterial taxa for colonization of vector-borne pathogens is well known, the disruption of the vector microbiota by host antibodies opens the possibility to develop novel transmission-blocking vaccines.

Anti-Microbiota Vaccine Reduces Avian Malaria Infection Within Mosquito Vectors

“…Host Abs and/or complement proteins have been detected in the guts of ticks (19)(20)(21)(22)(23)(24), mosquitoes (25,26), sandflies (27,28), and tsetse flies (29). Once ingested, host immune components can remain active from a few hours to months depending on the species of blood-sucking arthropod, raising the possibility that vertebrate Abs could interact with pathogens and microbiota (16). Empirical work shows that host Abs can target vector-borne pathogens within ticks (30) and mosquitoes (31)(32)(33).…”

“…Effective infection by vector-borne pathogens involves competent vectors, infective pathogens, and an infection-compatible microbiome (16). Mismatch of at least one of these components can result in an impaired ability of the vector to support the pathogen life cycle.…”

“…Although targeting specific commensal bacteria could block pathogen transmission, the lack of tools for the precise manipulation of the vector microbiota is currently a major limitation to developing novel transmission-blocking strategies. Specific host antibodies (Abs) are easily induced by vaccination, and once taken with the blood meal, they remain functional within the vector tissues and can bind symbionts ( 14 ) and other bacterial microbiota ( 15 ) within hematophagous arthropods ( 16 ). Surprisingly, host Abs specific to bacterial microbiota had never been used for microbiota manipulation and transmission blocking strategies ( 16 ).…”

Exploring the Ecological Implications of Microbiota Diversity in Birds: Natural Barriers Against Avian Malaria

“…What impact would mosquito microbiota modulation by anti-α-Gal Abs have on mosquito fitness and/or malaria transmission? Host antibodies taken in the blood meal can target pathogens and bacterial microbiota within hematophagous arthropods ( 52 ). Functional host antibodies have been shown to interact with symbionts in Rhodnius prolixus ( 53 ) and Glossina morsitans ( 54 ) as well as with bacterial microbiota in mosquitoes ( 55 ) and ticks ( 56 , 57 ).…”

“…Interestingly, Enterobacteriaceae (i.e., Escherichia - Shigella ) is shared by the microbiota of ticks and mosquitoes, but not of sandflies ( 58 ). Anti-microbiota vaccines are a microbiome manipulation tool for the induction of infection-refractory states in the vector microbiome ( 52 ). The evidence suggests that ingestion of avian anti-α-Gal Abs with the blood meal could target mosquito microbiota expressing α-Gal (e.g., Enterobacteriaceae) with a potential impact on Plasmodium colonization of mosquito tissues.…”