A novel vaccine against mosquito-borne Zika virus based on mosquito salivary gland protein AgBR1

PROJECT SUMMARYZika virus, an emerging flavivirus, is associated with severe clinical outcomes, including
Guillain-Barré syndrome and birth defects. Transmission of Zika virus is primarily mosquito-
borne. Mosquito salivary proteins are known to enhance infectivity and pathogenesis in Zika,
dengue and West Nile viruses by modulating immune responses. This proposal seeks to
develop a novel vaccine against Zika virus by targeting Aedes aegypti salivary gland proteins
important for Zika virus transmission from the mosquito vector to the mammalian host.Since we know that an antibody response towards certain, undescribed salivary gland
proteins can change flavivirus pathogenesis, we focused on antigenic salivary proteins that elicit
antibody responses in the vertebrate host. Using a yeast surface display screen, we identified 5
Ae. aegypti salivary proteins that react with sera from mice repeatedly bitten by this species of
mosquito. Passive immunization with antiserum against one of these proteins, AAEL001965,
which is also named Ae. aegypti bacteria-responsive protein 1 (AgBR1) resulted in significantly
more survival in mice infected with Zika virus by mosquito bite.In this proposal, we intend to carefully examine the protective effects of blocking the
mosquito AgBR1 protein in preventing severe mosquito-borne Zika virus infection in mice and
develop a strategy for actively immunizing mice against this protein 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 flavivirus and other arthropod-borne pathogens of medical
importance. These studies to define a vaccine to prevent Zika virus will be structured into the
following specific aimsPROJECT NARRATIVEZika is an emerging disease, transmitted by mosquitoes, which can cause severe
disease and birth defects. The goal of this project is to develop a vaccine against Zika virus that
would work by blocking the activity of a protein found in mosquito saliva.