High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure: Prevention of viremia

Robert A. Rasmussen, Nagadenahalli B. Siddappa, Samir K. Lakhashe, Jennifer Watkins, François Villinger, Chris Ibegbu, Ruth H. Florese, Marjorie Robert-Guroff, David C. Montefiori, Donald N. Forthal, David O'Connor, Ruth M. Ruprecht

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

OBJECTIVE:: To characterize the correlates of protection from systemic infection in a vaccinated rhesus macaque, RAt-9, which had been challenged sequentially with two related clade C simian/human immunodeficiency viruses (SHIV-Cs) yet remained aviremic for more than 5 years despite indirect evidence of cryptic infection. DESIGN:: To measure long-term anti-SHIV-C immunity, host genetics and gene-expression patterns for protective correlates. METHODS:: Long-term immune reactivity was evaluated and identification of virus in RAt-9 was attempted by RT-PCR analysis of concentrated plasma and blood transfer to CD8 cell-depleted infant macaques. Full MHC genotyping of RAt-9, TRIM5α and KIR3DL allelic expression analysis of PBMC, and microarray gene expression analysis were performed. RESULTS:: All attempts to detect/isolate virus, including blood transfer to CD8 cell-depleted infant rhesus macaques, were negative, and the animal maintained normal levels of memory CD4 T cells in both peripheral blood and gut tissues. However, RAt-9 maintained high levels of anti-SHIV-C humoral and cellular immunity, including reactivity to nonvaccine neoantigens (Nef and Rev), up to 63 months postinitial challenge, suggesting chronic sub-threshold infection. RAt-9 expressed the Mamu A*001 allele negative for B*008 and B*017, had a B13 serotype, and had increased expression of killer-cell immunoglobulin-like receptors (KIRs) previously linked to favorable outcomes of lentiviral infection. Elements of the gene expression profiling coincided with genotyping results. RAt-9 also displayed CD8 cell noncytotoxic antiviral response (CNAR) activity. CONCLUSION:: Monkey RAt-9 is the first example of a virus-exposed, persistently aviremic animal that has maintained long-term, high-level cellular and humoral antiviral immunity in the absence of an identifiable cryptic reservoir.

Original languageEnglish (US)
Pages (from-to)149-155
Number of pages7
JournalAIDS
Volume26
Issue number2
DOIs
Publication statusPublished - Jan 14 2012

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Keywords

  • AIDS
  • clade C
  • long-term immunity
  • prevention of viremia
  • simian/human immunodeficiency virus
  • vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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