Vaccine-elicited memory cytotoxic T lymphocytes contribute to Mamu-A*01-associated control of simian/human immunodeficiency virus 89.6P replication in rhesus monkeys.
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.
Seaman
Michael S
MS
Beth Israel Deaconess Medical Center, Division of Viral Pathogenesis, 330 Brookline Ave. RE-113, Boston, MA 02215, USA.
Santra
Sampa
S
Newberg
Michael H
MH
Philippon
Valerie
V
Manson
Kelledy
K
Xu
Ling
L
Gelman
Rebecca S
RS
Panicali
Dennis
D
Mascola
John R
JR
Nabel
Gary J
GJ
Letvin
Norman L
NL
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D017931:DNA Primers; D006678:HIV / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008253:Macaca mulatta; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication
D016915:AIDS Vaccines; D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; D012367:RNA, Viral