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

• Published in: Vaccines (Basel) Vol. 11; no. 3; p. 559
• Main Authors: Okagawa, Tomohiro, Konnai, Satoru, Nakamura, Hayato, Ganbaatar, Otgontuya, Sajiki, Yamato, Watari, Kei, Noda, Haruka, Honma, Mitsuru, Kato, Yukinari, Suzuki, Yasuhiko, Maekawa, Naoya, Murata, Shiro, Ohashi, Kazuhiko
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Animals; Antibodies; Antigens; Apoptosis; Blocking antibodies; Calves; Cattle; CD4 antigen; CD8 antigen; Cells; Combinatorial analysis; Cytokines; Disease transmission; Diseases; Dosage and administration; Effector cells; Genetic aspects; Growth; Immunotherapy; Infections; Infectious diseases; Ligands; live attenuated vaccine; Lymphocytes; Lymphocytes T; Medical research; Monoclonal antibodies; PD-1; PD-1 protein; PD-L1; PD-L1 protein; Prevention; T cell; Testing; Vaccines; Veterinary medicine; Viral antigens; Viral infections; Viral vaccines; Viruses; γ-Interferon; Japan; United States > US; live attenuated vaccine; PD-L1; cattle; PD-1; T cell; immunotherapy
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines11030559

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.