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Volume 6 Supplement 3

AIDS Vaccine 2009

P16-09. Adenovirus 5 vector HIV vaccination does not affect mucosal homing markers on Ad5-specific CD4+ T-cells in humans

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Background

The reasons for the recent failure of the Merck STEP trial, wherein Ad5-seropositive subjects demonstrated increased susceptibility to HIV infection, remain unclear. One potential hypothesis is that expansion and mucosal trafficking of Ad5-specific CD4+ T cells following Ad-vector immunization possibly rendered vaccinees more susceptible to HIV infection.

Methods

Ad-specific T cell responses were characterized in five seropositive and seronegative subjects from the Merck phase I 016 trial, the immediate STEP trial predecessor. Subjects received 3 × 1011 vector particles Merck Ad5 gag/pol/nef at weeks 0, 4 and 30. PBMC samples were obtained at weeks 0, 4, 8,18, 26, 30, 42, 52 and 78 relative to vaccination. T-cell responses to Ad were measured by stimulating PBMCs overnight with whole Ad vector before measuring functionality (IFN-γ, TNF-α, IL-2) memory phenotype (CD45RO, CCR7) and mucosal homing markers (α4, β7, CCR10, αE) by multicolor flow cytometry.

Results

There was no difference in the % of total or Ad-specific α4+β7+ CD4+ T-cells between seronpositive and seronegative subjects. There was also no increase in total or Ad-specific α4+β7+ CD4+ T-cells following vaccination. Ad-specific CD4+ T-cells comprised only 1–2% of total α4+β7+ cells in the blood. The memory phenotype of α4+β7+ was mixed between central memory, effector memory and effector CD4+ T-cells in both serogroups with no change in memory phenotype observed upon vaccination. CCR10 and CD103 were expressed at marginal levels on Ad-specific CD4+ T cells.

Conclusion

This data suggests that vaccination does not induce a differential measurable effect on mucosal trafficking in circulating Ad-specific CD4+ T cells between the serogroups and therefore contradicts a role for Ad-specific T-cells in the possible increased risk of HIV infection observed during the STEP trial.

Author information

Correspondence to N Hutnick.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Hutnick, N., Carnathan, D., Dubey, S. et al. P16-09. Adenovirus 5 vector HIV vaccination does not affect mucosal homing markers on Ad5-specific CD4+ T-cells in humans. Retrovirology 6, P238 (2009). https://doi.org/10.1186/1742-4690-6-S3-P238

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Keywords

  • Effector Memory
  • Measurable Effect
  • Central Memory
  • Vector Particle
  • Memory Phenotype