Zika virus, an emerging flavivirus, is associated with severe clinical outcomes, including Guillain-Barr 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 aims

Public Health Relevance

Zika 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
1R41AI142846-01
Application #
9678043
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Woodson, Sara Elaine
Project Start
2019-01-21
Project End
2020-12-31
Budget Start
2019-01-21
Budget End
2019-12-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
L2 Diagnostics, LLC
Department
Type
DUNS #
142406110
City
New Haven
State
CT
Country
United States
Zip Code
06530