ADCC Develops Over Time during Persistent Infection with Live-Attenuated SIV and Is Associated with Complete Protection against SIV(mac)251 Challenge
AuthorsAlpert, Michael D.
Harvey, Jackson D.
Lauer, W. Anderson
Reeves, R. Keith
Piatak, Michael Jr.
Mansfield, Keith G.
Lifson, Jeffrey D.
Desrosiers, Ronald C.
Johnson, R. Paul
Evans, David T.
UMass Chan AffiliationsDepartment of Medicine, Division of Preventive and Behavioral Medicine
Document TypeJournal Article
KeywordsAntibody-Dependent Cell Cytotoxicity
Simian immunodeficiency virus
Immunology and Infectious Disease
MetadataShow full item record
AbstractLive-attenuated strains of simian immunodeficiency virus (SIV) routinely confer apparent sterilizing immunity against pathogenic SIV challenge in rhesus macaques. Understanding the mechanisms of protection by live-attenuated SIV may provide important insights into the immune responses needed for protection against HIV-1. Here we investigated the development of antibodies that are functional against neutralization-resistant SIV challenge strains, and tested the hypothesis that these antibodies are associated with protection. In the absence of detectable neutralizing antibodies, Env-specific antibody-dependent cell-mediated cytotoxicity (ADCC) emerged by three weeks after inoculation with SIVDeltanef, increased progressively over time, and was proportional to SIVDeltanef replication. Persistent infection with SIVDeltanef elicited significantly higher ADCC titers than immunization with a non-persistent SIV strain that is limited to a single cycle of infection. ADCC titers were higher against viruses matched to the vaccine strain in Env, but were measurable against viruses expressing heterologous Env proteins. In two separate experiments, which took advantage of either the strain-specificity or the time-dependent maturation of immunity to overcome complete protection against SIV(mac)251 challenge, measures of ADCC activity were higher among the SIVDeltanef-inoculated macaques that remained uninfected than among those that became infected. These observations show that features of the antibody response elicited by SIVDeltanef are consistent with hallmarks of protection by live-attenuated SIV, and reveal an association between Env-specific antibodies that direct ADCC and apparent sterilizing protection by SIVDeltanef.
SourcePLoS Pathog. 2012 Aug;8(8):e1002890. Epub 2012 Aug 23. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/44825
Related ResourcesLink to Article in PubMed
RightsCopyright: © Alpert et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.