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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Rasmussen, RA; Siddappa, NB; Lakhashe, SK; Watkins, J; Villinger, F; Ibegbu, C; Florese, RH; Robert-Guroff, M; Montefiori, DC; Forthal, DN; O'Connor, D; Ruprecht, RM; Clade C Program Project Group,

Published Date

  • January 14, 2012

Published In

Volume / Issue

  • 26 / 2

Start / End Page

  • 149 - 155

PubMed ID

  • 21941166

Pubmed Central ID

  • 21941166

Electronic International Standard Serial Number (EISSN)

  • 1473-5571

Digital Object Identifier (DOI)

  • 10.1097/QAD.0b013e32834d3c4f

Language

  • eng

Conference Location

  • England