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

Prevention of viremia

Robert A. Rasmussen, Siddappa Nagadenahalli Byrareddy, Samir K. Lakhashe, Jennifer Watkins, François Villinger, Chris Ibegbu, Ruth H. Florese, Marjorie Robert-Guroff, David C. Montefiori, Donald N. Forthal, David O'Connor, Ruth M. Ruprecht

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)149-155
Number of pages7
JournalAIDS
Volume26
Issue number2
DOIs
StatePublished - Jan 14 2012

Fingerprint

AIDS Vaccines
Viremia
Antiviral Agents
Immunity
Viruses
Humoral Immunity
Infection
Macaca mulatta
KIR Receptors
Gene Expression
Simian Immunodeficiency Virus
Macaca
Gene Expression Profiling
Microarray Analysis
Cellular Immunity
Haplorhini
Alleles
HIV
T-Lymphocytes
Polymerase Chain Reaction

Keywords

  • AIDS
  • clade C
  • long-term immunity
  • prevention of viremia
  • simian/human immunodeficiency virus
  • vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure : Prevention of viremia. / Rasmussen, Robert A.; Byrareddy, Siddappa Nagadenahalli; Lakhashe, Samir K.; Watkins, Jennifer; Villinger, François; Ibegbu, Chris; Florese, Ruth H.; Robert-Guroff, Marjorie; Montefiori, David C.; Forthal, Donald N.; O'Connor, David; Ruprecht, Ruth M.

In: AIDS, Vol. 26, No. 2, 14.01.2012, p. 149-155.

Research output: Contribution to journalArticle

Rasmussen, RA, Byrareddy, SN, Lakhashe, SK, Watkins, J, Villinger, F, Ibegbu, C, Florese, RH, Robert-Guroff, M, Montefiori, DC, Forthal, DN, O'Connor, D & Ruprecht, RM 2012, '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, pp. 149-155. https://doi.org/10.1097/QAD.0b013e32834d3c4f
Rasmussen, Robert A. ; Byrareddy, Siddappa Nagadenahalli ; Lakhashe, Samir K. ; Watkins, Jennifer ; Villinger, François ; Ibegbu, Chris ; Florese, Ruth H. ; Robert-Guroff, Marjorie ; Montefiori, David C. ; Forthal, Donald N. ; O'Connor, David ; Ruprecht, Ruth M. / High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure : Prevention of viremia. In: AIDS. 2012 ; Vol. 26, No. 2. pp. 149-155.
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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.",
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AU - Rasmussen, Robert A.

AU - Byrareddy, Siddappa Nagadenahalli

AU - Lakhashe, Samir K.

AU - Watkins, Jennifer

AU - Villinger, François

AU - Ibegbu, Chris

AU - Florese, Ruth H.

AU - Robert-Guroff, Marjorie

AU - Montefiori, David C.

AU - Forthal, Donald N.

AU - O'Connor, David

AU - Ruprecht, Ruth M.

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N2 - 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.

AB - 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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