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    Timing of Immune Escape Linked to Success or Failure of Vaccination

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    Author
    Reece, JC; Loh, L; Alcantara, S; Fernandez, CS; Stambas, J; Sexton, A; De Rose, R; Petravic, J; Davenport, MP; Kent, SJ
    Date
    2010-09-16
    Source Title
    PLoS One
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Reece, Jeanette; Loh, Liyen; Alcantara, Sheilajen; Fernandez, Caroline; Stambas, John; SEXTON, AMY; De Rose, Robert; Kent, Stephen
    Affiliation
    Melbourne School of Population and Global Health
    Microbiology and Immunology
    School of Biomedical Sciences
    Chemical and Biomolecular Engineering
    Metadata
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    Document Type
    Journal Article
    Citations
    Reece, J. C., Loh, L., Alcantara, S., Fernandez, C. S., Stambas, J., Sexton, A., De Rose, R., Petravic, J., Davenport, M. P. & Kent, S. J. (2010). Timing of Immune Escape Linked to Success or Failure of Vaccination. PLOS ONE, 5 (9), https://doi.org/10.1371/journal.pone.0012774.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/264026
    DOI
    10.1371/journal.pone.0012774
    Abstract
    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 SIV(mac251) 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 SIV(mac251) 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.

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