Live Attenuated Rev-Independent Nef¯SIV Enhances Acquisition of Heterologous SIVsmE660 in Acutely Vaccinated Rhesus Macaques
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Author
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.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1371/journal.pone.0075556Metadata
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Byrareddy, S. N., M. Ayash-Rashkovsky, V. G. Kramer, S. J. Lee, M. Correll, F. J. Novembre, F. Villinger, et al. 2013. “Live Attenuated Rev-Independent Nef¯SIV Enhances Acquisition of Heterologous SIVsmE660 in Acutely Vaccinated Rhesus Macaques.” PLoS ONE 8 (9): e75556. doi:10.1371/journal.pone.0075556. http://dx.doi.org/10.1371/journal.pone.0075556.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787041/pdf/Terms of Use
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