Vaccine-elicited memory cytotoxic T lymphocytes contribute to Mamu-A*01-associated control of simian/human immunodeficiency virus 89.6P replication in rhesus monkeys

Michael S. Seaman, Sampa Santra, Michael H. Newberg, Valerie Philippon, Kelledy Manson, Ling Xu, Rebecca S. Gelman, Dennis Panicali, John R. Mascola, Gary J. Nabel, Norman L. Letvin

Research output: Contribution to journalArticle

Abstract

The expression of particular major histocompatibility complex (MHC) class I alleles can influence the rate of disease progression following lentiviral infections. This effect is a presumed consequence of potent cytotoxic T-lymphocyte (CTL) responses that are restricted by these MHC class I molecules. The present studies have examined the impact of the MHC class I allele Mamu-A*01 on simian/human immunodeficiency virus 89.6P (SHIV-89.6P) infection in unvaccinated and vaccinated rhesus monkeys by exploring the contribution of dominant-epitope specific CTL in this setting. Expression of Mamu-A*01 in immunologically naive monkeys was not associated with improved control of viral replication, CD4+ T-lymphocyte loss, or survival. In contrast, Mamu-A*01+ monkeys that had received heterologous prime/boost immunizations prior to challenge maintained higher CD4+ T-lymphocyte levels and better control of SHIV-89.6P replication than Mamu-A*01- monkeys. This protection was associated with the evolution of high-frequency anamnestic CTL responses specific for a dominant Mamu-A*01-restricted Gag epitope following infection. These data indicate that specific MHC class I alleles can confer protection in the setting of a pathogenic SHIV infection by their ability to elicit memory CTL following vaccination.

Original languageEnglish (US)
Pages (from-to)4580-4588
Number of pages9
JournalJournal of Virology
Volume79
Issue number8
DOIs
StatePublished - Apr 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Seaman, M. S., Santra, S., Newberg, M. H., Philippon, V., Manson, K., Xu, L., Gelman, R. S., Panicali, D., Mascola, J. R., Nabel, G. J., & Letvin, N. L. (2005). Vaccine-elicited memory cytotoxic T lymphocytes contribute to Mamu-A*01-associated control of simian/human immunodeficiency virus 89.6P replication in rhesus monkeys. Journal of Virology, 79(8), 4580-4588. https://doi.org/10.1128/JVI.79.8.4580-4588.2005