A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys

Santra, Sampa and Korber, Bette T. and Muldoon, Mark and Barouch, Dan H. and Nabel, Gary J. and Gao, Feng and Hahn, Beatrice H. and Haynes, Barton F. and Letvin, Norman L. (2008) A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys. Proceedings of the National Academy of Sciences of the USA, 105 (30). pp. 10489-10494. ISSN 0027-8424

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Abstract

One of the major challenges that must be met in developing an HIV-1 vaccine is devising a strategy to generate cellular immunity with sufficient breadth to deal with the extraordinary genetic diversity of the virus. Amino acids in the envelopes of viruses from the same clade can differ by >15%, and those from different clades can differ by >30%. It has been proposed that creating immunogens using centralized HIV-1 gene sequences might provide a practical solution to this problem. Such centralized genes can be generated by employing a number of different strategies: consensus, ancestral, or center of tree sequences. These computer-generated sequences are a shorter genetic distance from any two contemporary virus sequences than those contemporary sequences are from each other. The present study was initiated to evaluate the breadth of cellular immunity generated through immunization of rhesus monkeys with vaccine constructs expressing either an HIV-1 global consensus envelope sequence (CON-S) or a single patient isolate clade B envelope sequence (clade B). We show that vaccine immunogens expressing the single centralized gene CON-S generated cellular immune responses with significantly increased breadth compared with immunogens expressing a wild-type virus gene. In fact, CON-S immunogens elicited cellular immune responses to 3- to 4-fold more discrete epitopes of the envelope proteins from clades A, C, and G than did clade B immunogens. These findings suggest that immunization with centralized genes is a promising vaccine strategy for developing a global vaccine for HIV-1 as well as vaccines for other genetically diverse viruses.

Item Type:	Article
Additional Information:	This is an Open Access article: use the DOI link above to download a copy from the journal's web site.
Uncontrolled Keywords:	HIV, consensus gene, 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:	20 Aug 2008
Last Modified:	20 Oct 2017 14:12
URI:	https://eprints.maths.manchester.ac.uk/id/eprint/1138

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