Dramatic rise in plasma viremia after CD8+ T cell depletion in simian immunodeficiency virus-infected macaques
Xia Jin,Daniel E. Bauer,Sarah Tuttleton,Sharon R Lewin,Agegnehu Gettie,James Blanchard,Craig E. Irwin,Jeffrey T. Safrit,John E. Mittler,Leor S. Weinberger,Leondios G. Kostrikis,Linqi Zhang,Alan S. Perelson,David D. Ho +13 more
TLDR
It is demonstrated that CD8 cells play a crucial role in suppressing SIV replication in vivo and are examined using an anti-CD8 monoclonal antibody, OKT8F.Abstract:
To determine the role of CD8(+) T cells in controlling simian immunodeficiency virus (SIV) replication in vivo, we examined the effect of depleting this cell population using an anti-CD8 monoclonal antibody, OKT8F. There was on average a 99.9% reduction of CD8 cells in peripheral blood in six infected Macaca mulatta treated with OKT8F. The apparent CD8 depletion started 1 h after antibody administration, and low CD8 levels were maintained until day 8. An increase in plasma viremia of one to three orders of magnitude was observed in five of the six macaques. The injection of a control antibody to an infected macaque did not induce a sustained viral load increase, nor did it significantly reduce the number of CD8(+) T cells. These results demonstrate that CD8 cells play a crucial role in suppressing SIV replication in vivo.read more
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Ultradeep Pyrosequencing Detects Complex Patterns of CD8+ T-Lymphocyte Escape in Simian Immunodeficiency Virus-Infected Macaques
Benjamin N. Bimber,Benjamin J. Burwitz,Shelby L. O’Connor,Ann M. Detmer,Emma Gostick,Simon M. Lank,David Price,Austin L. Hughes,David H. O’Connor +8 more
TL;DR: This work uses ultradeep pyrosequencing to create a comprehensive picture of CD8+ T-lymphocyte (CD8-TL) escape in SIV-infected macaques, revealing a previously undetected complex pattern of viral variants.
Journal ArticleDOI
Cross-Subtype T-Cell Immune Responses Induced by a Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen
Eric A. Weaver,Zhongjing Lu,Zenaido T. Camacho,Fatiha Moukdar,Hua-Xin Liao,Ben Jiang Ma,Mark Muldoon,James Theiler,Gary J. Nabel,Norman L. Letvin,Bette T. Korber,Bette T. Korber,Beatrice H. Hahn,Barton F. Haynes,Feng Gao +14 more
TL;DR: Though the limited major histocompatibility complex repertoire in inbred mice does not necessarily predict responses in nonhuman primates and humans, results suggest that synthetic centralized env immunogens represent a promising approach for HIV-1 vaccine design that merits further characterization.
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A Phase I Double Blind, Placebo-Controlled, Randomized Study of a Multigenic HIV-1 Adenovirus Subtype 35 Vector Vaccine in Healthy Uninfected Adults
Michael C. Keefer,Jill Gilmour,Peter Hayes,Dilbinder K. Gill,Jakub Kopycinski,Hannah Cheeseman,Michelle Cashin-Cox,Marloes A. Naarding,Lorna Clark,Natalia Fernandez,Catherine A. Bunce,Christine M. Hay,Sabrina Welsh,Wendy Komaroff,Lottie Hachaambwa,Tony Tarragona-Fiol,Eddy Sayeed,Devika Zachariah,James Ackland,Kelley Loughran,Burc Barin,Emmanuel Cormier,Josephine H. Cox,Patricia E. Fast,Jean-Louis Excler +24 more
TL;DR: HIV-specific cellular and humoral responses were seen in the majority of volunteers immunized with Ad 35-GRIN/ENV or Ad35- GRIN and increased after the second vaccination, and reactogenicity was dose-related.
Journal ArticleDOI
Heterogeneity and fate choice: T cell exhaustion in cancer and chronic infections.
Mary Philip,Andrea Schietinger +1 more
TL;DR: Recent findings on heterogeneity of tumor-specific T cells and exhausted T cells during chronic infections are reviewed, discussing distinct differentiation state dynamics, fate choices, and functional states.
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Enhanced Potency of Plasmid DNA Microparticle Human Immunodeficiency Virus Vaccines in Rhesus Macaques by Using a Priming-Boosting Regimen with Recombinant Proteins
Gillis R. Otten,Mary Schaefer,Barbara Doe,Hong Liu,Indresh K. Srivastava,Jan zur Megede,Jina Kazzaz,Ying Lian,Manmohan Singh,Mildred Ugozzoli,David C. Montefiori,Mark G. Lewis,David A. Driver,Thomas W. Dubensky,John M. Polo,John J. Donnelly,Derek T. O'Hagan,Susan W. Barnett,Jeffrey B. Ulmer +18 more
TL;DR: PLG microparticles are an effective means of delivering DNA vaccines in nonhuman primates, as demonstrated for two different types of DNA vaccines encoding two different antigens, and are compatible for use with DNA prime-protein boost regimens.
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