Immunoglobulins Delivered by AAV Vector for the Prevention of SIV Infection

Project: Research project

Description

DESCRIPTION (provided by applicant): AAV vector has recently been used to deliver single chain Fv immunoadhesin (scFVI) versions of rhesus monkey antibodies with neutralizing activity against SIV. High, persisting levels of scFVI were achieved in 6 of 9 rhesus monkeys and these six exhibited a sterilizing barrier against SIV challenge. Three of the nine monkeys developed antibody responses to the scFVI that they received and these three were not protected against SIV challenge. Two different approaches will be compared for AAV vector delivery of the authentic IgG version of these scFVIs. We will determine whether delivery of authentic IgG decreases the frequency with which anti-anti responses are observed. We will determine whether AAV vector can be used to deliver dimeric secretory IgA and whether secretory IgA provides a more effective barrier to SIV infection by the mucosal route. Finally, we will determine whether antibody-dependent cellular cytotoxicity is important for the protective effects of the IgG versions of 4L6 and 5L7. Results from these experiments in rhesus monkeys will inform and guide development of analogous vectors for the prevention of HIV-1 infection in humans. PUBLIC HEALTH RELEVANCE: Successful strategies have not been devised for the elicitation of antibodies with potent broadly-neutralizing activity against field strains of HIV-1. Use of AAV vector to deliver predefined antibodies with potent, broadly-neutralizing activity is a novel promising strategy for creating a sterilizing barrier to HIV-1 infection. Results from the proposed experiments in rhesus monkeys will inform and guide development of such vectors for the prevention of HIV-1 infection in humans.
StatusActive
Effective start/end date7/18/1211/30/21

Funding

  • National Institutes of Health: $731,021.00
  • National Institutes of Health: $731,021.00
  • National Institutes of Health: $810,091.00
  • National Institutes of Health: $710,565.00
  • National Institutes of Health: $731,021.00
  • National Institutes of Health: $710,565.00
  • National Institutes of Health: $667,931.00

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Immunoglobulins
Macaca mulatta
Single-Chain Antibodies
Dependovirus
Infection
HIV-1
Secretory Immunoglobulin A
Immunoglobulin G
Neutralizing Antibodies
Antibodies
Antibody Formation
Haplorhini
Transgenes
HIV Infections
HIV Antibodies
Viral Proteins
Virus Diseases
Immunity
Immunization
Vaccines

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)