601. HIV-specific CD8 T cell cross-reactivity following Ad5-based vaccination is shaped by vaccine regimen and prior Ad5 exposure
Session: Poster Abstract Session: HIV: Pathogenesis and Inflammation
Thursday, October 5, 2017
Room: Poster Hall CD
Posters
  • 2017 IDWeek_Boppana.pdf (1.6 MB)
  • Background: A major obstacle to developing an HIV vaccine is its enormous viral diversity. As such, the ability of the CD8 T cell response to cross-recognize several variants of a single epitope could be an important factor in optimizing future vaccine design. Some prior work has indicated that CD8 cross-reactivity may play a role in viral control in individuals with protective HLA-I alleles; however, not much is known about CD8 cross-reactivity in the context of HIV vaccination.

    Methods: We examined the CD8 T cell cross-reactivity in recipients of two prior preventative HIV-1 vaccine studies, both of which used adenovirus serotype 5 (Ad5) vectors: HVTN 502 (MRKAd5) and HVTN 505 (VRC DNA with Ad5 boost). We measured the responses to vaccine-encoded epitopes and their common variants using IFNγ ELISpot assays. We also quantified the antigen sensitivities by measuring the IFNγ responses to log fold serial peptide dilutions.

    Results: Overall, CD8 responses to variant epitopes had a lower magnitude and decreased antigen sensitivity than those targeting vaccine-encoded epitopes (p<0.0001 and p=0.014). A greater number of mutations, less conservative amino acid substitutions, and HLA-I driven mutations negatively affect the immunogenicity of cross-reactive responses (p<0.0001, p=0.0003, and p<0.0001, respectively). Additionally, cross-reactive responses had a higher magnitude in MRKAd5 recipients with low pre-existing Ad5 titers than those with high pre-existing titers (p=0.0230). Among that former MRKAd5 group, cross-reactive responses were decreased in magnitude and proportion in comparison with cross-reactive responses of VRC DNA/Ad5 recipients (p=0.0052, p=0.0488), even though both groups’ responses to vaccine-encoded epitopes had similar magnitudes.

    Conclusion: Our data shows that cross-reactive responses are frequently elicited by vaccination and that this cross-reactivity is affected by the vaccine regimen and by pre-existing Ad5 titers. Future work will focus on analyzing the TCR clonotype repertoire responsible for these CD8 T cell responses and establishing the biologic and clinical significance of these vaccine-induced cross-reactive CD8 T cells.

    Sushma Boppana, BA, FIDSA, Sarah Sterett, BS, Kai Qin, BS, Anju Bansal, PhD and Paul Goepfert, MD, Medicine, University of Alabama at Birmingham, Birmingham, AL

    Disclosures:

    S. Boppana, None

    S. Sterett, None

    K. Qin, None

    A. Bansal, None

    P. Goepfert, None

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