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

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Title: Enhancement of Vaccine-Induced T-Cell Responses by PD-L1 Blockade in Calves
Authors: Okagawa, Tomohiro Browse this author →KAKEN DB
Konnai, Satoru Browse this author →KAKEN DB
Nakamura, Hayato Browse this author
Ganbaatar, Otgontuya Browse this author
Sajiki, Yamato Browse this author
Watari, Kei Browse this author
Noda, Haruka Browse this author
Honma, Mitsuru Browse this author
Kato, Yukinari Browse this author
Suzuki, Yasuhiko Browse this author →KAKEN DB
Maekawa, Naoya Browse this author →KAKEN DB
Murata, Shiro Browse this author →KAKEN DB
Ohashi, Kazuhiko Browse this author →KAKEN DB
Keywords: PD-L1
T cell
live attenuated vaccine
Issue Date: 1-Mar-2023
Publisher: MDPI
Journal Title: Vaccines
Volume: 11
Issue: 3
Start Page: 559
Publisher DOI: 10.3390/vaccines11030559
Abstract: 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 gamma delta TCR+ T cells was enhanced by the combination of vaccination and PD-L1 blockade. In addition, IFN-gamma 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.
Type: article
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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