SBIR-STTR Award

A Novel Vaccine Against Mosquito-Borne Zika Virus Based on Mosquito Salivary Gland Protein AGBR1
Award last edited on: 11/17/2023

Sponsored Program
STTR
Awarding Agency
NIH : NIAID
Total Award Amount
$2,562,068
Award Phase
2
Solicitation Topic Code
855
Principal Investigator
Erol Fikrig

Company Information

L2 Diagnostics LLC (AKA: L-Two Diagnostics LLC)

300 George Street Unit 309
New Haven, CT 06511
   (203) 494-5288
   l2dx@aol.com
   www.l2dx.com

Research Institution

Yale University

Phase I

Contract Number: 1R41AI142846-01
Start Date: 1/21/2019    Completed: 12/31/2020
Phase I year
2019
Phase I Amount
$299,888
Zika 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 aims

Public Health Relevance Statement:
PROJECT NARRATIVE 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.

Project Terms:
Active Immunization; Adjuvant; Aedes; Affinity; Aluminum Hydroxide; Antibodies; Antibody Response; Antigens; Arthropods; Bacteria; base; Bite; Cells; Chromatography; Clinical; Congenital Abnormality; Culicidae; Dengue; Disease; Dose; Drosophila genus; Flavivirus; Goals; Guillain-Barré Syndrome; Human; Immune response; Immune Sera; Immunization; Immunize; Immunoglobulin G; improved; Infection prevention; Medical; Methods; Modeling; mosquito-borne; mouse model; Mus; Names; nonhuman primate; novel vaccines; Outcome; Passive Immunization; pathogen; Pathogenesis; Phase; phase 2 study; prevent; protective effect; Proteins; Recombinants; Regimen; Saliva; Salivary Proteins; Schedule; Serum; Structure; Subcutaneous Injections; success; Surface; System; Testing; transmission process; vaccine candidate; Vaccine Design; vaccine development; vaccine efficacy; vaccine trial; Vaccines; vector mosquito; viral transmission; Viremia; West Nile virus; Work; Yeasts; Zika Virus; ZIKV infection

Phase II

Contract Number: 5R41AI142846-02
Start Date: 1/21/2019    Completed: 12/31/2021
Phase II year
2020
(last award dollars: 2023)
Phase II Amount
$2,262,180

Zika 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 aims

Public Health Relevance Statement:
PROJECT NARRATIVE 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.

Project Terms:
Active Immunization; Adjuvant; Aedes; Affinity; Aluminum Hydroxide; Antibodies; Antibody Response; Antigens; Arthropods; Bacteria; base; Bite; Cells; Chromatography; Clinical; Congenital Abnormality; Culicidae; Dengue; Disease; Dose; Drosophila genus; Flavivirus; Goals; Guillain-Barré Syndrome; Human; Immune response; Immune Sera; Immunization; Immunize; Immunoglobulin G; improved; Infection prevention; Medical; Methods; Modeling; mosquito-borne; mouse model; Mus; Names; nonhuman primate; novel vaccines; Outcome; Passive Immunization; pathogen; Pathogenesis; Phase; phase 2 study; prevent; protective effect; Proteins; Recombinants; Regimen; Saliva; Salivary Proteins; Schedule; Serum; Structure; Subcutaneous Injections; success; Surface; System; Testing; transmission process; vaccine candidate; Vaccine Design; vaccine development; vaccine efficacy; vaccine trial; Vaccines; vector mosquito; viral transmission; Viremia; West Nile virus; Work; Yeasts; Zika Virus; ZIKV infection