Immunogenicity Study of Glycoprotein-Deficient Rabies Virus Expressing Simian/Human Immunodeficiency Virus SHIV 89.6P Envelope in a Rhesus Macaque

Author:

McKenna Philip M.1,Aye Pyone Pyone2,Dietzschold Bernhard1,Montefiori David C.3,Martin Louis N.2,Marx Preston A.2,Pomerantz Roger J.45,Lackner Andrew2,Schnell Matthias J.4

Affiliation:

1. Departments of Microbiology

2. Tulane National Primate Research Center, Covington, Louisiana

3. Department of Surgery, Duke University, Durham, North Carolina

4. Biochemistry and Molecular Pharmacology

5. Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania

Abstract

ABSTRACT Rabies virus (RV) has recently been developed as a novel vaccine candidate for human immunodeficiency virus type 1 (HIV-1). The RV glycoprotein (G) can be functionally replaced by HIV-1 envelope glycoprotein (Env) if the gp160 cytoplasmic domain (CD) of HIV-1 Env is replaced by that of RV G. Here, we describe a pilot study of the in vivo replication and immunogenicity of an RV with a deletion of G (ΔG) expressing a simian/human immunodeficiency virus SHIV 89.6P Env ectodomain and transmembrane domain fused to the RV G CD (ΔG-89.6P-RVG) in a rhesus macaque. An animal vaccinated with ΔG-89.6P-RVG developed SHIV 89.6P virus-neutralizing antibodies and SHIV 89.6P -specific cellular immune responses after challenge with SHIV 89.6P . There was no evidence of CD4 + T-cell loss, and plasma viremia was controlled to undetectable levels by 6 weeks postchallenge and has remained suppressed out to 22 weeks postchallenge.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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