Immunization with Single-Cycle SIV Significantly Reduces Viral Loads After an Intravenous Challenge with SIVmac239

PLoS Pathogens

Jeffrey D. Lifson¹  Michael Piatak Jr.¹  Wenjun Li²  Barbra A. Richardson³  Eloísa Yuste⁴  Sharon K. Ng⁴  M. Quinn DeGottardi⁴  David T. Evans⁴  Bin Jia⁴  Keith G. Mansfield⁵  Angela Carville⁵ 

[1] AIDS and Cancer Virus Program, SAIC Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland, United States of America;Biostatistics Research Group, Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America;Department of Biostatistics, University of Washington, Seattle, Washington, United States of America;Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts, United States of America;Department of Pathology, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts, United States of America

关键词: T cells;    SIV;    Vesicular stomatitis virus;    Antibodies;    Immune response;    Viral load;    Enzyme-linked immunoassays;    Viral replication;   

DOI  :  10.1371/journal.ppat.1000272

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection were evaluated for the ability to elicit protective immunity against wild-type SIVmac239 infection of rhesus macaques by two different vaccine regimens. Six animals were inoculated at 8-week intervals with 6 identical doses consisting of a mixture of three different envelope variants of single-cycle SIV (scSIV). Six additional animals were primed with a mixture of cytoplasmic domain-truncated envelope variants of scSIV and boosted with two doses of vesicular stomatitis virus glycoprotein (VSV G) trans-complemented scSIV. While both regimens elicited detectable virus-specific T cell responses, SIV-specific T cell frequencies were more than 10-fold higher after boosting with VSV G trans-complemented scSIV (VSV G scSIV). Broad T cell recognition of multiple viral antigens and Gag-specific CD4+ T cell responses were also observed after boosting with VSV G scSIV. With the exception of a single animal in the repeated immunization group, all of the animals became infected following an intravenous challenge with SIVmac239. However, significantly lower viral loads and higher memory CD4+ T cell counts were observed in both immunized groups relative to an unvaccinated control group. Indeed, both scSIV immunization regimens resulted in containment of SIVmac239 replication after challenge that was as good as, if not better than, what has been achieved by other non-persisting vaccine vectors that have been evaluated in this challenge model. Nevertheless, the extent of protection afforded by scSIV was not as good as typically conferred by persistent infection with live, attenuated SIV. These observations have potentially important implications to the design of an effective AIDS vaccine, since they suggest that ongoing stimulation of virus-specific immune responses may be essential to achieving the degree of protection afforded by live, attenuated SIV.

【 授权许可】

CC BY