Adenovirus serotype 5 vaccine vectors trigger IL-27–dependent inhibitory CD4+ T cell responses that impair CD8+ T cell function

Rafael A. Larocca; Nicholas M. Provine; Malika Aid; M. Justin Iampietro; Erica N. Borducchi; Alexander Badamchi-Zadeh; Peter Abbink; David Ng’ang’a; Christine A. Bricault; Eryn Blass; Pablo Penaloza-MacMaster; Kathryn E. Stephenson; Dan H. Barouch

doi:10.1126/sciimmunol.aaf7643

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Rejuvenating viral vectors

Adenovirus serotype 5 (Ad5) vaccine vectors elicit mixed responses—they induce protective CD8⁺ T cells, but these cells may be partially exhausted. Now, Larocca et al. demonstrate that this exhausted phenotype may result from Ad5 vector–induced antigen-specific CD4⁺ T cells that express interleukin-10 (IL-10) and programmed cell death 1 (PD-1) in both mice and macaques. These IL-10⁺CD4⁺ T cells suppress the vaccine-induced CD8⁺ T cell response, and their inhibitory function may depend in part on IL-27. These data suggest that targeting this inhibitory pathway may enhance protection of viral vector–based vaccines.

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Adenovirus serotype 5 vaccine vectors trigger IL-27–dependent inhibitory CD4⁺ T cell responses that impair CD8⁺ T cell function

Rejuvenating viral vectors

Science Immunology

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