Vaccination against Zika virus infection using mosquito NeSt1 protein

Arthropod-borne viruses (arboviruses) present a substantial threat to human and animal health
worldwide. They are transmitted by hematophagous arthropods, in which mosquitoes are one of
the main transmitters. The mosquito specie, Aedes aegypti, is the primary mosquito vector of
several widely spread arboviruses as zika, dengue or West Nile viruses. Mosquitoes transmit
these pathogens by inoculating virus-infected saliva into host skin during probing and
feeding. This saliva contains over one hundred unique proteins and these proteins have diverse
functions, including facilitating blood feed. Some of these proteins are known to enhance
infectivity and pathogenesis in Zika and other arboviruses by modulating immune responses, and
the development of blocking therapies against them could be a good approach to reduce
infectivity and pathogenesis in the host. In addition, focusing on mosquito proteins as vaccine
targets can overcome the problems associated with the use of viral antigens as a vaccine targets,
due to their high variability.
In this proposal, we will develop a novel transmission-blocking vaccine against Zika virus (ZIKV)
by targeting A. aegypti bacteria responsive protein 1 (AgBR1) and A. aegypti neutrophil
stimulating factor 1 (NeSt1) salivary gland protein. Using a yeast surface display screen, we
identified a set of A. aegypti salivary proteins that react with sera from mice repeatedly bitten by
A. aegypti mosquitoes. Passive immunization with antiserum against two of these proteins,
AgBR1 and NeSt1, resulted in significantly more survival in mice infected with ZIKV by mosquito
bite. Simultaneous passive immunization with both antisera demonstrated a synergy resulting in
higher survival than expected from the individual treatments.
Based on these results, in this proposal we intend to carefully examine the protective effects of
blocking the mosquito AgBR1 and NeSt1 proteins in preventing severe mosquito-borne ZIKV
infection in mice. We will develop a strategy for actively immunizing mice against both proteins
towards the development of a vaccine for use in humans. The success of this approach also offers
a functional paradigm for developing vaccines against other flaviviruses and other arthropod-
borne pathogens of medical importance.Mosquito-borne viruses present a substantial threat to human and animal health worldwide. Some
mosquito saliva proteins are known to enhance infectivity and pathogenesis of Zika and other
arboviruses by modulating immune responses. Here, we propose to develop a vaccine candidate
against the mosquito salivary proteins NeSt1 and AgBR1 to prevent Zika virus transmission in a
mouse model.