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Vaccination against Zika virus infection using mosquito NeSt1 protein

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI152904-01A1
Agency Tracking Number: R41AI152904
Amount: $299,200.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA19-270
Timeline
Solicitation Year: 2019
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-06-16
Award End Date (Contract End Date): 2022-05-31
Small Business Information
300 GEORGE ST STE 309
New Haven, CT 06511-6662
United States
DUNS: 142406110
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 MICHEL LEDIZET
 (203) 503-0383
 mledizet@l2dx.com
Business Contact
 MARTIN MATTESSICH
Phone: (203) 494-5288
Email: mmattessich@l2dx.com
Research Institution
 YALE UNIVERSITY
 
OFFICE OF SPONSORED PROJECTS, PO BOX 208327
NEW HAVEN, CT 06520-8327
United States

 Nonprofit college or university
Abstract

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.

* Information listed above is at the time of submission. *

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