title: High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure:  prevention of viremia.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rasmussen
authors.forename: Nagadenahalli B
authors.initials: NB
authors.lastname: Siddappa
authors.forename: Samir K
authors.initials: SK
authors.lastname: Lakhashe
authors.forename: Jennifer
authors.initials: J
authors.lastname: Watkins
authors.forename: François
authors.initials: F
authors.lastname: Villinger
authors.forename: Chris
authors.initials: C
authors.lastname: Ibegbu
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Florese
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Donald N
authors.initials: DN
authors.lastname: Forthal
authors.forename: David
authors.initials: D
authors.lastname: O'Connor
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D015967:Gene Expression Regulation, Viral / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004279:DNA, Viral