Image_2_Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys.TIF (202.94 kB)

Image_2_Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys.TIF

Download (202.94 kB)
figure
posted on 23.10.2018 by Enxiang Pan, Fengling Feng, Pingchao Li, Qing Yang, Xiuchang Ma, Chunxiu Wu, Jin Zhao, Hongbin Yan, Rulei Chen, Ling Chen, Caijun Sun

Though immune correlates for protection are still under investigation, potent cytotoxic T lymphocyte responses are desirable for an ideal HIV-1 vaccine. PD-1 blockade enhances SIV-specific CD8+ T cells. However, little information has been reported about how it affects the immunogenicity and protection of prophylactic SIV vaccines in nonhuman primates. Here, we show that PD-1 blockade during vaccination substantially improved protective efficacy in SIV challenged macaques. The PD-1 pathway was blocked using a monoclonal antibody specific to human PD-1. Administration of this antibody effectively augmented and sustained vaccine-induced SIV-specific T cell responses for more than 42 weeks after first immunization in rhesus monkeys, as compared with SIV vaccination only. Importantly, after intrarectally repeated low-dosage challenge with highly pathogenic SIVmac239, monkeys with PD-1 blockade during vaccination achieved full protection against incremental viral doses of up to 50,000 TICD50. These findings highlight the importance of PD-1 blockade during vaccination for the development of HIV vaccines.

History

References

Licence

Exports