Engineering Recombinant Reoviruses To Display gp41 Membrane-Proximal External-Region Epitopes from HIV-1

Author:

Boehme Karl W.12,Ikizler Mine'12,Iskarpatyoti Jason A.12,Wetzel J. Denise12,Willis Jordan34,Crowe James E.145,LaBranche Celia C.678,Montefiori David C.678,Wilson Gregory J.12,Dermody Terence S.125

Affiliation:

1. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA

2. Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA

3. Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA

4. Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA

5. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

6. Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA

7. Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA

8. Laboratory for AIDS Vaccine Research and Development, Duke University Medical Center, Durham, North Carolina, USA

Abstract

Vaccines to protect against HIV-1, the causative agent of AIDS, are not approved for use. Antibodies that neutralize genetically diverse strains of HIV-1 bind to discrete regions of the envelope glycoproteins, including the gp41 MPER. We engineered recombinant reoviruses that displayed MPER epitopes in attachment protein σ1 (REO-MPER vectors). The REO-MPER vectors replicated with wild-type efficiency, were genetically stable, and retained native antigenicity. However, we did not detect HIV-1-specific immune responses following inoculation of the REO-MPER vectors into small animals. This work provides proof of principle for engineering reovirus to express antigenic epitopes and illustrates the difficulty in eliciting MPER-specific immune responses.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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