Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys

Santra, Sampa and Liao, Hua-Xin and Zhang, Ruijin and Muldoon, Mark and Watson, Sydeaka and Fischer, Will and Theiler, James and Szinger, James and Balachandran, Harikrishnan and Buzby, Adam and Quinn, David and Parks, Robert J. and Tsao, Chun-Yen and Carville, Angela and Mansfield, Keith G. and Pavlakis, George N. and Felber, Barbara K. and Haynes, Barton F. and Korber, Bette T. and Letvin, Norman L. (2010) Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys. Nature Medicine, 16 (3). pp. 324-328. ISSN 1546-170X

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Abstract

An effective HIV vaccine must elicit immune responses that recognize genetically diverse viruses. It must generate CD8+ T lymphocytes that control HIV replication and CD4+ T lymphocytes that provide help for the generation and maintenance of both cellular and humoral immune responses against the virus. Creating immunogens that can elicit cellular immune responses against the genetically varied circulating isolates of HIV presents a key challenge for creating an HIV vaccine. Polyvalent mosaic immunogens derived by in silico recombination of natural strains of HIV are designed to induce cellular immune responses that recognize genetically diverse circulating virus isolates8. Here we immunized rhesus monkeys by plasmid DNA prime and recombinant vaccinia virus boost with vaccine constructs expressing either consensus or polyvalent mosaic proteins. As compared to consensus immunogens, the mosaic immunogens elicited CD8+ T lymphocyte responses to more epitopes of each viral protein than did the consensus immunogens and to more variant sequences of CD8+ T lymphocyte epitopes. This increased breadth and depth of epitope recognition may contribute both to protection against infection by genetically diverse viruses and to the control of variant viruses that emerge as they mutate away from recognition by cytotoxic T lymphocytes.

Item Type:	Article
Additional Information:	Advance online publication appeared 21 Feb. 2010.
Uncontrolled Keywords:	HIV-1, mosaic vaccine, cytotoxic T lymphocyte
Subjects:	MSC 2010, the AMS's Mathematics Subject Classification > 92 Biology and other natural sciences
Depositing User:	Dr Mark Muldoon
Date Deposited:	23 Feb 2010
Last Modified:	20 Oct 2017 14:12
URI:	https://eprints.maths.manchester.ac.uk/id/eprint/1421

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