Protective Efficacy of a Single Immunization of a Chimeric Adenovirus Vector-Based Vaccine against Simian Immunodeficiency Virus Challenge in Rhesus Monkeys

Author:

Barouch Dan H.12,Liu Jinyan1,Lynch Diana M.1,O'Brien Kara L.1,La Porte Annalena1,Simmons Nathaniel L.1,Riggs Ambryice M.1,Clark Sarah1,Abbink Peter1,Montefiori David C.3,Landucci Gary4,Forthal Donald N.4,Self Steven G.5,Carville Angela6,Mansfield Keith6,Goudsmit Jaap7

Affiliation:

1. Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215

2. Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts 02214

3. Duke University Medical Center, Durham, North Carolina 27710

4. University of California, Irvine School of Medicine, Irvine, California 92697

5. Department of Biostatistics, University of Washington, Seattle, Washington 98109

6. New England Primate Research Center, Southborough, MA 01772

7. Crucell Holland BV, 2301 CA, Leiden, The Netherlands

Abstract

ABSTRACT Rare serotype and chimeric recombinant adenovirus (rAd) vectors that evade anti-Ad5 immunity are currently being evaluated as potential vaccine vectors for human immunodeficiency virus type 1 and other pathogens. We have recently reported that a heterologous rAd prime-boost regimen expressing simian immunodeficiency virus (SIV) Gag afforded durable partial immune control of an SIV challenge in rhesus monkeys. However, single-shot immunization may ultimately be preferable for global vaccine delivery. We therefore evaluated the immunogenicity and protective efficacy of a single immunization of chimeric rAd5 hexon hypervariable region 48 (rAd5HVR48) vectors expressing SIV Gag, Pol, Nef, and Env against a homologous SIV challenge in rhesus monkeys. Inclusion of Env resulted in improved control of peak and set point SIV RNA levels following challenge. In contrast, DNA vaccine priming did not further improve the protective efficacy of rAd5HVR48 vectors in this system.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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