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

• Authors: Robert A. Rasmussen, Dana Farber Cancer Institute; Nagadenahalli B. Siddappa, Dana Farber Cancer Institute; Samir K. Lakhashe, Dana Farber Cancer Institute; Jennifer Watkins, Dana Farber Cancer Institute; Francois Villinger, Emory University; Chris Ibegbu, Emory University; Ruth H. Florese, National Cancer Institute; Marjorie Robert-Guroff, National Cancer Institute; David C. Montefiori, Duke University; Donald N. Forthal, University of California, Irvine; David O'Connor, University of Wisconsin; Ruth M. Ruprecht, Dana Farber Cancer Institute
• Journal Title: AIDS
• Volume: Volume 26, Number 2
• Publisher: Lippincott, Williams & Wilkins | 2012-01-14, Pages 149-155
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1097/QAD.0b013e32834d3c4f
• Subjects: Biology, Virology; Health Sciences, Immunology; Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Infectious Diseases; Virology; AIDS; clade C; long-term immunity; prevention of viremia; simian/human immunodeficiency virus; vaccine; SIMIAN-IMMUNODEFICIENCY-VIRUS; CLADE-C ENV; RHESUS MACAQUES; ANTIRETROVIRAL THERAPY; HIV VACCINES; HLA-B; REPLICATION; ANTIBODIES; INFECTION; LYMPHOCYTES

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.