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

Publication ,  Journal Article
Rasmussen, RA; Siddappa, NB; Lakhashe, SK; Watkins, J; Villinger, F; Ibegbu, C; Florese, RH; Robert-Guroff, M; Montefiori, DC; Forthal, DN ...
Published in: AIDS
January 14, 2012

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.

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Published In

AIDS

DOI

EISSN

1473-5571

Publication Date

January 14, 2012

Volume

26

Issue

2

Start / End Page

149 / 155

Location

England

Related Subject Headings

  • Virology
  • Viremia
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Reverse Transcriptase Polymerase Chain Reaction
  • Macaca mulatta
  • HIV-1
  • Gene Expression Regulation, Viral
  • DNA, Viral
 

Citation

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Chicago
ICMJE
MLA
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Rasmussen, R. A., Siddappa, N. B., Lakhashe, S. K., Watkins, J., Villinger, F., Ibegbu, C., … Clade C Program Project Group, . (2012). High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure: prevention of viremia. AIDS, 26(2), 149–155. https://doi.org/10.1097/QAD.0b013e32834d3c4f
Rasmussen, Robert A., Nagadenahalli B. Siddappa, Samir K. Lakhashe, Jennifer Watkins, François Villinger, Chris Ibegbu, Ruth H. Florese, et al. “High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure: prevention of viremia.AIDS 26, no. 2 (January 14, 2012): 149–55. https://doi.org/10.1097/QAD.0b013e32834d3c4f.
Rasmussen RA, Siddappa NB, Lakhashe SK, Watkins J, Villinger F, Ibegbu C, et al. High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure: prevention of viremia. AIDS. 2012 Jan 14;26(2):149–55.
Rasmussen, Robert A., et al. “High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure: prevention of viremia.AIDS, vol. 26, no. 2, Jan. 2012, pp. 149–55. Pubmed, doi:10.1097/QAD.0b013e32834d3c4f.
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. High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure: prevention of viremia. AIDS. 2012 Jan 14;26(2):149–155.

Published In

AIDS

DOI

EISSN

1473-5571

Publication Date

January 14, 2012

Volume

26

Issue

2

Start / End Page

149 / 155

Location

England

Related Subject Headings

  • Virology
  • Viremia
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Reverse Transcriptase Polymerase Chain Reaction
  • Macaca mulatta
  • HIV-1
  • Gene Expression Regulation, Viral
  • DNA, Viral