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Author Notes:

Ruth M. Ruprecht, MD, PhD, Dana-Farber Cancer Institute, 450 Brookline Avenue, JFB-809, Boston MA 02215 USA. Tel.: +1 617 632 3719; fax: +1 617 632 3112; ruth_ruprecht@dfci.harvard.edu.

We thank Dr. Welkin Johnson and the Genetics Core of the New England Primate Research Center ((NEPRC) Southborough, Massachusetts) for TRIM5α genotyping; Drs. Reddy Gali, Center for Biomedical Informatics, Harvard Medical School, for help in microarray analyses; Susan Stephenson and Aftab Ansari for the determination of the KIR3DL alleles; and Mark Wilson for supplying REm-6 samples; and Gary Landucci and Candi Trac (UC Irvine) for technical assistance.

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Research Funding:

Support is acknowledged by NIH grants PO1 AI048240 to R.A.R., S.L.H, J.G.E. and R.M.R.; RR-00165 to the YNPRC; RR00168 to the NEPRC; and by Center for AIDS Research Immunology Core grants, P30 AI060354 and P30 AI050409.

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

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

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Journal Title:

AIDS

Volume:

Volume 26, Number 2

Publisher:

, Pages 149-155

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2012 Lippincott Williams & Wilkins, Inc.

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