stambas-timingofimmune-2010.pdf (566.93 kB)
Timing of immune escape linked to success or failure of vaccination
journal contribution
posted on 2010-09-01, 00:00 authored by J Reece, L Loh, S Alcantara, C Fernandez, John StambasJohn Stambas, A Sexton, R De Rose, J Petravic, M Davenport, S KentSuccessful vaccination against HIV should limit viral replication sufficiently to prevent the emergence of viral immune escape mutations. Broadly directed immunity is likely to be required to limit opportunities for immune escape variants to flourish. We studied the emergence of an SIV Gag cytotoxic T cell immune escape variant in pigtail macaques expressing the Mane-A*10 MHC I allele using a quantitative RT-PCR to measure viral loads of escape and wild type variants. Animals receiving whole Gag expressing vaccines completely controlled an SIVmac251 challenge, had broader CTL responses and exhibited minimal CTL escape. In contrast, animals vaccinated with only a single CTL epitope and challenged with the same SIVmac251 stock had high levels of viral replication and rapid CTL escape. Unvaccinated naïve animals exhibited a slower emergence of immune escape variants. Thus narrowly directed vaccination against a single epitope resulted in rapid immune escape and viral levels equivalent to that of naïve unvaccinated animals. These results emphasize the importance of inducing broadly directed HIV-specific immunity that effectively quashes early viral replication and limits the generation of immune escape variants. This has important implications for the selection of HIV vaccines for expanded human trials.
History
Journal
Plos oneVolume
5Issue
9Pagination
1 - 7Publisher
Public Library of ScienceLocation
San Francisco, Calif.ISSN
1932-6203Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2010, Public Library of ScienceUsage metrics
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