Timing of immune escape linked to success or failure of vaccination

Reece, Jeanette C., Loh, Liyen, Alcantara, Sheilajen, Fernandez, Caroline S., Stambas, John, Sexton, Amy, De Rose, Robert, Petravic, Janka, Davenport, Miles P. and Kent, Stephen J. 2010, Timing of immune escape linked to success or failure of vaccination, Plos one, vol. 5, no. 9, pp. 1-7.

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Title Timing of immune escape linked to success or failure of vaccination
Author(s) Reece, Jeanette C.
Loh, Liyen
Alcantara, Sheilajen
Fernandez, Caroline S.
Stambas, John
Sexton, Amy
De Rose, Robert
Petravic, Janka
Davenport, Miles P.
Kent, Stephen J.
Journal name Plos one
Volume number 5
Issue number 9
Start page 1
End page 7
Publisher Public Library of Science
Place of publication San Francisco, Calif.
Publication date 2010-09
ISSN 1932-6203
Summary Successful 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.
Language eng
Field of Research 110704 Cellular Immunology
Socio Economic Objective 920109 Infectious Diseases
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2010, Reece et al.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30031115

Document type: Journal Article
Collection: School of Medicine
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