Genetic imprint of vaccination on simian/human immunodeficiency virus type 1 transmitted viral genomes in Rhesus Macaques

Varela, M. et al. (2013) Genetic imprint of vaccination on simian/human immunodeficiency virus type 1 transmitted viral genomes in Rhesus Macaques. PLoS ONE, 8(8), e70814. (doi: 10.1371/journal.pone.0070814) (PMID:23967111) (PMCID:PMC3743870)

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Understanding the genetic, antigenic and structural changes that occur during HIV-1 infection in response to pre-existing immunity will facilitate current efforts to develop an HIV-1 vaccine. Much is known about HIV-1 variation at the population level but little with regard to specific changes occurring in the envelope glycoprotein within a host in response to immune pressure elicited by antibodies. The aim of this study was to track and map specific early genetic changes occurring in the viral envelope gene following vaccination using a highly controlled viral challenge setting in the SHIV macaque model. We generated 449 full-length env sequences from vaccinees, and 63 from the virus inoculum. Analysis revealed a different pattern in the distribution and frequency of mutations in the regions of the envelope gene targeted by the vaccine as well as different patterns of diversification between animals in the naïve control group and vaccinees. Given the high stringency of the model it is remarkable that we were able to identify genetic changes associated with the vaccination. This work provides insight into the characterization of breakthrough viral populations in less than fully efficacious vaccines and illustrates the value of HIV-1 Env SHIV challenge model in macaques to unravel the mechanisms driving HIV-1 envelope genetic diversity in the presence of vaccine induced-responses.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Willett, Professor Brian and Hughes, Dr Joseph and Varela, Dr Mariana
Authors: Varela, M., Verschoor, E., Lai, R.P.J., Hughes, J., Mooj, P., McKinley, T., Fitzmaurice, T.J., Landskron, L., Willett, B.J., Frost, S.D.W., Bogers, W.M., and Heeney, J.L.
Subjects:Q Science > QR Microbiology > QR355 Virology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in PLoS ONE 8(8):e70814
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
579911Predicting Vaccine Escape: Improving Strategic Vaccine DesignMariana VarelaWellcome Trust (WELLCOME)085206/Z/08/ZMVLS III - CENTRE FOR VIRUS RESEARCH
471561The virus-receptor interaction in lentiviral pathogenesis and immunityBrian WillettWellcome Trust (WELLCOME)084272/Z/07/ZMVLS III - CENTRE FOR VIRUS RESEARCH