Live Attenuated Rev-Independent Nef-SIV Enhances Acquisition of Heterologous SIVsmE660 in Acutely Vaccinated Rhesus Macaques

Siddappa N. Byrareddy, Mila Ayash-Rashkovsky, Victor G. Kramer, Sandra J. Lee, Mick Correll, Francis J. Novembre, Francois Villinger, Welkin E. Johnson, Agneta von Gegerfelt, Barbara K. Felber, Ruth M. Ruprecht

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Abstract

Background:Rhesus macaques (RMs) inoculated with live-attenuated Rev-Independent Nef- simian immunodeficiency virus (Rev-Ind Nef-SIV) as adults or neonates controlled viremia to undetectable levels and showed no signs of immunodeficiency over 6-8 years of follow-up. We tested the capacity of this live-attenuated virus to protect RMs against pathogenic, heterologous SIVsmE660 challenges.Methodology/Principal Findings:Three groups of four RM were inoculated with Rev-Ind Nef-SIV and compared. Group 1 was inoculated 8 years prior and again 15 months before low dose intrarectal challenges with SIVsmE660. Group 2 animals were inoculated with Rev-Ind Nef-SIV at 15 months and Group 3 at 2 weeks prior to the SIVsmE660 challenges, respectively. Group 4 served as unvaccinated controls. All RMs underwent repeated weekly low-dose intrarectal challenges with SIVsmE660. Surprisingly, all RMs with acute live-attenuated virus infection (Group 3) became superinfected with the challenge virus, in contrast to the two other vaccine groups (Groups 1 and 2) (P=0.006 for each) and controls (Group 4) (P=0.022). Gene expression analysis showed significant upregulation of innate immune response-related chemokines and their receptors, most notably CCR5 in Group 3 animals during acute infection with Rev-Ind Nef-SIV.Conclusions/Significance:We conclude that although Rev-Ind Nef-SIV remained apathogenic, acute replication of the vaccine strain was not protective but associated with increased acquisition of heterologous mucosal SIVsmE660 challenges.

Original languageEnglish (US)
Article numbere75556
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 30 2013

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Macaca mulatta
Viruses
Animals
Vaccines
viruses
X-Linked Combined Immunodeficiency Diseases
Chemokine Receptors
vaccines
Simian immunodeficiency virus
Simian Immunodeficiency Virus
Gene expression
Viremia
viremia
immunosuppression
Virus Diseases
chemokines
dosage
Innate Immunity
infection
animals

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Byrareddy, S. N., Ayash-Rashkovsky, M., Kramer, V. G., Lee, S. J., Correll, M., Novembre, F. J., ... Ruprecht, R. M. (2013). Live Attenuated Rev-Independent Nef-SIV Enhances Acquisition of Heterologous SIVsmE660 in Acutely Vaccinated Rhesus Macaques. PloS one, 8(9), [e75556]. https://doi.org/10.1371/journal.pone.0075556

Live Attenuated Rev-Independent Nef-SIV Enhances Acquisition of Heterologous SIVsmE660 in Acutely Vaccinated Rhesus Macaques. / Byrareddy, Siddappa N.; Ayash-Rashkovsky, Mila; Kramer, Victor G.; Lee, Sandra J.; Correll, Mick; Novembre, Francis J.; Villinger, Francois; Johnson, Welkin E.; von Gegerfelt, Agneta; Felber, Barbara K.; Ruprecht, Ruth M.

In: PloS one, Vol. 8, No. 9, e75556, 30.09.2013.

Research output: Contribution to journalArticle

Byrareddy, SN, Ayash-Rashkovsky, M, Kramer, VG, Lee, SJ, Correll, M, Novembre, FJ, Villinger, F, Johnson, WE, von Gegerfelt, A, Felber, BK & Ruprecht, RM 2013, 'Live Attenuated Rev-Independent Nef-SIV Enhances Acquisition of Heterologous SIVsmE660 in Acutely Vaccinated Rhesus Macaques', PloS one, vol. 8, no. 9, e75556. https://doi.org/10.1371/journal.pone.0075556
Byrareddy, Siddappa N. ; Ayash-Rashkovsky, Mila ; Kramer, Victor G. ; Lee, Sandra J. ; Correll, Mick ; Novembre, Francis J. ; Villinger, Francois ; Johnson, Welkin E. ; von Gegerfelt, Agneta ; Felber, Barbara K. ; Ruprecht, Ruth M. / Live Attenuated Rev-Independent Nef-SIV Enhances Acquisition of Heterologous SIVsmE660 in Acutely Vaccinated Rhesus Macaques. In: PloS one. 2013 ; Vol. 8, No. 9.
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abstract = "Background:Rhesus macaques (RMs) inoculated with live-attenuated Rev-Independent Nef- simian immunodeficiency virus (Rev-Ind Nef-SIV) as adults or neonates controlled viremia to undetectable levels and showed no signs of immunodeficiency over 6-8 years of follow-up. We tested the capacity of this live-attenuated virus to protect RMs against pathogenic, heterologous SIVsmE660 challenges.Methodology/Principal Findings:Three groups of four RM were inoculated with Rev-Ind Nef-SIV and compared. Group 1 was inoculated 8 years prior and again 15 months before low dose intrarectal challenges with SIVsmE660. Group 2 animals were inoculated with Rev-Ind Nef-SIV at 15 months and Group 3 at 2 weeks prior to the SIVsmE660 challenges, respectively. Group 4 served as unvaccinated controls. All RMs underwent repeated weekly low-dose intrarectal challenges with SIVsmE660. Surprisingly, all RMs with acute live-attenuated virus infection (Group 3) became superinfected with the challenge virus, in contrast to the two other vaccine groups (Groups 1 and 2) (P=0.006 for each) and controls (Group 4) (P=0.022). Gene expression analysis showed significant upregulation of innate immune response-related chemokines and their receptors, most notably CCR5 in Group 3 animals during acute infection with Rev-Ind Nef-SIV.Conclusions/Significance:We conclude that although Rev-Ind Nef-SIV remained apathogenic, acute replication of the vaccine strain was not protective but associated with increased acquisition of heterologous mucosal SIVsmE660 challenges.",
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AU - Kramer, Victor G.

AU - Lee, Sandra J.

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AU - Johnson, Welkin E.

AU - von Gegerfelt, Agneta

AU - Felber, Barbara K.

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N2 - Background:Rhesus macaques (RMs) inoculated with live-attenuated Rev-Independent Nef- simian immunodeficiency virus (Rev-Ind Nef-SIV) as adults or neonates controlled viremia to undetectable levels and showed no signs of immunodeficiency over 6-8 years of follow-up. We tested the capacity of this live-attenuated virus to protect RMs against pathogenic, heterologous SIVsmE660 challenges.Methodology/Principal Findings:Three groups of four RM were inoculated with Rev-Ind Nef-SIV and compared. Group 1 was inoculated 8 years prior and again 15 months before low dose intrarectal challenges with SIVsmE660. Group 2 animals were inoculated with Rev-Ind Nef-SIV at 15 months and Group 3 at 2 weeks prior to the SIVsmE660 challenges, respectively. Group 4 served as unvaccinated controls. All RMs underwent repeated weekly low-dose intrarectal challenges with SIVsmE660. Surprisingly, all RMs with acute live-attenuated virus infection (Group 3) became superinfected with the challenge virus, in contrast to the two other vaccine groups (Groups 1 and 2) (P=0.006 for each) and controls (Group 4) (P=0.022). Gene expression analysis showed significant upregulation of innate immune response-related chemokines and their receptors, most notably CCR5 in Group 3 animals during acute infection with Rev-Ind Nef-SIV.Conclusions/Significance:We conclude that although Rev-Ind Nef-SIV remained apathogenic, acute replication of the vaccine strain was not protective but associated with increased acquisition of heterologous mucosal SIVsmE660 challenges.

AB - Background:Rhesus macaques (RMs) inoculated with live-attenuated Rev-Independent Nef- simian immunodeficiency virus (Rev-Ind Nef-SIV) as adults or neonates controlled viremia to undetectable levels and showed no signs of immunodeficiency over 6-8 years of follow-up. We tested the capacity of this live-attenuated virus to protect RMs against pathogenic, heterologous SIVsmE660 challenges.Methodology/Principal Findings:Three groups of four RM were inoculated with Rev-Ind Nef-SIV and compared. Group 1 was inoculated 8 years prior and again 15 months before low dose intrarectal challenges with SIVsmE660. Group 2 animals were inoculated with Rev-Ind Nef-SIV at 15 months and Group 3 at 2 weeks prior to the SIVsmE660 challenges, respectively. Group 4 served as unvaccinated controls. All RMs underwent repeated weekly low-dose intrarectal challenges with SIVsmE660. Surprisingly, all RMs with acute live-attenuated virus infection (Group 3) became superinfected with the challenge virus, in contrast to the two other vaccine groups (Groups 1 and 2) (P=0.006 for each) and controls (Group 4) (P=0.022). Gene expression analysis showed significant upregulation of innate immune response-related chemokines and their receptors, most notably CCR5 in Group 3 animals during acute infection with Rev-Ind Nef-SIV.Conclusions/Significance:We conclude that although Rev-Ind Nef-SIV remained apathogenic, acute replication of the vaccine strain was not protective but associated with increased acquisition of heterologous mucosal SIVsmE660 challenges.

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