Vaccines (Mar 2023)

Enhancement of Vaccine-Induced T-Cell Responses by PD-L1 Blockade in Calves

  • Tomohiro Okagawa,
  • Satoru Konnai,
  • Hayato Nakamura,
  • Otgontuya Ganbaatar,
  • Yamato Sajiki,
  • Kei Watari,
  • Haruka Noda,
  • Mitsuru Honma,
  • Yukinari Kato,
  • Yasuhiko Suzuki,
  • Naoya Maekawa,
  • Shiro Murata,
  • Kazuhiko Ohashi

DOI
https://doi.org/10.3390/vaccines11030559
Journal volume & issue
Vol. 11, no. 3
p. 559

Abstract

Read online

Interactions between programmed death 1 (PD-1) and PD-ligand 1 (PD-L1) cause functional exhaustion of T cells by inducing inhibitory signals, thereby attenuating effector functions of T cells. We have developed an anti-bovine PD-L1 blocking antibody (Ab) and have demonstrated that blockade of the interaction between PD-1 and PD-L1 reactivates T-cell responses in cattle. In the present study, we examined the potential utility of PD-1/PD-L1-targeted immunotherapy in enhancing T-cell responses to vaccination. Calves were inoculated with a hexavalent live-attenuated viral vaccine against bovine respiratory infections in combination with treatment with an anti-PD-L1 Ab. The expression kinetics of PD-1 in T cells and T-cell responses to viral antigens were measured before and after vaccination to evaluate the adjuvant effect of anti-PD-L1 Ab. PD-1 expression was upregulated in vaccinated calves after the administration of a booster vaccination. The activation status of CD4+, CD8+, and γδTCR+ T cells was enhanced by the combination of vaccination and PD-L1 blockade. In addition, IFN-γ responses to viral antigens were increased following combinatorial vaccination with PD-L1 blockade. In conclusion, the blockade of the PD-1/PD-L1 interaction enhances T-cell responses induced by vaccination in cattle, indicating the potential utility of anti-PD-L1 Ab in improving the efficacy of current vaccination programs.

Keywords