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PLoS One. 2014 Mar 20;9(3):e92012. doi: 10.1371/journal.pone.0092012. eCollection 2014.

Vaccination against endogenous retrotransposable element consensus sequences does not protect rhesus macaques from SIVsmE660 infection and replication.

Author information

1
Vaccine Research, Worldwide R&D, Pfizer Inc., San Diego, California, United States of America.
2
Department of Immunology, University of Toronto, Toronto, ON, Canada.
3
Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America.
4
Wisconsin National Primate Center, University of Wisconsin, Madison, Wisconsin, United States of America.
5
Division of Biostatistics, Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, Oregon, United States of America.
6
Division of Experiment Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America.
7
Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America; Department of Medical Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.

Abstract

The enormous sequence diversity of HIV remains a major roadblock to the development of a prophylactic vaccine and new approaches to induce protective immunity are needed. Endogenous retrotransposable elements (ERE) such as endogenous retrovirus K (ERV)-K and long interspersed nuclear element-1 (LINE-1) are activated during HIV-1-infection and could represent stable, surrogate targets to eliminate HIV-1-infected cells. Here, we explored the hypothesis that vaccination against ERE would protect macaques from acquisition and replication of simian immunodeficiency virus (SIV). Following vaccination with antigens derived from LINE-1 and ERV-K consensus sequences, animals mounted immune responses that failed to delay acquisition of SIVsmE660. We observed no differences in acute or set point viral loads between ERE-vaccinated and control animals suggesting that ERE-specific responses were not protective. Indeed, ERE-specific T cells failed to expand anamnestically in vivo following infection with SIVsmE660 and did not recognize SIV-infected targets in vitro, in agreement with no significant induction of targeted ERE mRNA by SIV in macaque CD4+ T cells. Instead, lower infection rates and viral loads correlated significantly to protective TRIM5α alleles. Cumulatively, these data demonstrate that vaccination against the selected ERE consensus sequences in macaques did not lead to immune-mediated recognition and killing of SIV-infected cells, as has been shown for HIV-infected human cells using patient-derived HERV-K-specific T cells. Thus, further research is required to identify the specific nonhuman primate EREs and retroviruses that recapitulate the activity of HIV-1 in human cells. These results also highlight the complexity in translating observations of the interplay between HIV-1 and human EREs to animal models.

PMID:
24651676
PMCID:
PMC3961289
DOI:
10.1371/journal.pone.0092012
[Indexed for MEDLINE]
Free PMC Article
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