No evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys

Norman L. Letvin, Srini S. Rao, Vi Dang, Adam P. Buzby, Birgit Korioth-Schmitz, Dilani Dombagoda, Jenny G. Parvani, Ryon H. Clarke, Liat Bar, Kevin R. Carlson, Pamela A. Kozlowski, Vanessa M. Hirsch, John R. Mascola, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

Defining the immune correlates of the protection against human immunodeficiency virus type 1 (HIV-1) acquisition in individuals who are exposed to HIV-1 but do not become infected may provide important direction for the creation of an HIV-1 vaccine. We have employed the simian immunodeficiency virus (SIV)/rhesus monkey model to determine whether monkeys can be repeatedly exposed to a primate lentivirus by a mucosal route and escape infection and whether virus-specific immune correlates of protection from infection can be identified in uninfected monkeys. Five of 18 rhesus monkeys exposed 18 times by intrarectal inoculation to SIVmac251 or SIVsmE660 were resistant to infection, indicating that the exposed/uninfected phenotype can be reproduced in a nonhuman primate AIDS model. However, routine peripheral blood lymphocyte gamma interferon enzyme-linked immunospot (ELISPOT), tetramer, and intracellular cytokine staining assays, as well as cytokine-augmented ELISPOT and peptide-stimulated tetramer assays, failed to define a systemic antigen-specific cellular immune correlate to this protection. Further, local cell-mediated immunity could not be demonstrated by tetramer assays of these protected monkeys, and local humoral immunity was not associated with protection against acquisition of virus in another cohort of mucosally exposed monkeys. Therefore, resistance to mucosal infection in these monkeys may not be mediated by adaptive virus-specific immune mechanisms. Rather, innate immune mechanisms or an intact epithelial barrier may be responsible for protection against mucosal infection in this population of monkeys.

Original languageEnglish (US)
Pages (from-to)12368-12374
Number of pages7
JournalJournal of Virology
Volume81
Issue number22
DOIs
StatePublished - Nov 2007
Externally publishedYes

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Macaca mulatta
Haplorhini
monkeys
Immunity
immunity
Viruses
viruses
Human immunodeficiency virus 1
HIV-1
infection
Infection
Primates
assays
cytokines
Primate Lentiviruses
Cytokines
Lentivirus
Virus Diseases

ASJC Scopus subject areas

  • Immunology

Cite this

Letvin, N. L., Rao, S. S., Dang, V., Buzby, A. P., Korioth-Schmitz, B., Dombagoda, D., ... Nabel, G. J. (2007). No evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys. Journal of Virology, 81(22), 12368-12374. https://doi.org/10.1128/JVI.00822-07

No evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys. / Letvin, Norman L.; Rao, Srini S.; Dang, Vi; Buzby, Adam P.; Korioth-Schmitz, Birgit; Dombagoda, Dilani; Parvani, Jenny G.; Clarke, Ryon H.; Bar, Liat; Carlson, Kevin R.; Kozlowski, Pamela A.; Hirsch, Vanessa M.; Mascola, John R.; Nabel, Gary J.

In: Journal of Virology, Vol. 81, No. 22, 11.2007, p. 12368-12374.

Research output: Contribution to journalArticle

Letvin, NL, Rao, SS, Dang, V, Buzby, AP, Korioth-Schmitz, B, Dombagoda, D, Parvani, JG, Clarke, RH, Bar, L, Carlson, KR, Kozlowski, PA, Hirsch, VM, Mascola, JR & Nabel, GJ 2007, 'No evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys', Journal of Virology, vol. 81, no. 22, pp. 12368-12374. https://doi.org/10.1128/JVI.00822-07
Letvin, Norman L. ; Rao, Srini S. ; Dang, Vi ; Buzby, Adam P. ; Korioth-Schmitz, Birgit ; Dombagoda, Dilani ; Parvani, Jenny G. ; Clarke, Ryon H. ; Bar, Liat ; Carlson, Kevin R. ; Kozlowski, Pamela A. ; Hirsch, Vanessa M. ; Mascola, John R. ; Nabel, Gary J. / No evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys. In: Journal of Virology. 2007 ; Vol. 81, No. 22. pp. 12368-12374.
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