Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys
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 protect...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-10-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02415/full |
| _version_ | 1819178850270052352 |
|---|---|
| author | Enxiang Pan Enxiang Pan Fengling Feng Fengling Feng Pingchao Li Qing Yang Xiuchang Ma Chunxiu Wu Jin Zhao Hongbin Yan Rulei Chen Ling Chen Ling Chen Caijun Sun Caijun Sun |
| author_facet | Enxiang Pan Enxiang Pan Fengling Feng Fengling Feng Pingchao Li Qing Yang Xiuchang Ma Chunxiu Wu Jin Zhao Hongbin Yan Rulei Chen Ling Chen Ling Chen Caijun Sun Caijun Sun |
| author_sort | Enxiang Pan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T21:49:06Z |
| format | Article |
| id | doaj.art-84b80f52b20044b7b8d3c285fd3f87c8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T21:49:06Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-84b80f52b20044b7b8d3c285fd3f87c82022-12-21T18:11:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-10-01910.3389/fimmu.2018.02415413202Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus MonkeysEnxiang Pan0Enxiang Pan1Fengling Feng2Fengling Feng3Pingchao Li4Qing Yang5Xiuchang Ma6Chunxiu Wu7Jin Zhao8Hongbin Yan9Rulei Chen10Ling Chen11Ling Chen12Caijun Sun13Caijun Sun14State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaSchool of Life Sciences, University of Science and Technology of China, Hefei, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaSchool of Public Health (Shenzhen), Sun Yat-sen University, Guangdong, ChinaGenor Biopharma Co. Ltd., Shanghai, ChinaGenor Biopharma Co. Ltd., Shanghai, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaThe Guangzhou 8th People's Hospital & The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaSchool of Public Health (Shenzhen), Sun Yat-sen University, Guangdong, ChinaThough 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.02415/fullPD-1 blockadeHIV vaccineCTLNHP modelSIV challenge |
| spellingShingle | Enxiang Pan Enxiang Pan Fengling Feng Fengling Feng Pingchao Li Qing Yang Xiuchang Ma Chunxiu Wu Jin Zhao Hongbin Yan Rulei Chen Ling Chen Ling Chen Caijun Sun Caijun Sun Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys Frontiers in Immunology PD-1 blockade HIV vaccine CTL NHP model SIV challenge |
| title | Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys |
| title_full | Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys |
| title_fullStr | Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys |
| title_full_unstemmed | Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys |
| title_short | Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys |
| title_sort | immune protection of siv challenge by pd 1 blockade during vaccination in rhesus monkeys |
| topic | PD-1 blockade HIV vaccine CTL NHP model SIV challenge |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02415/full |
| work_keys_str_mv | AT enxiangpan immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT enxiangpan immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT fenglingfeng immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT fenglingfeng immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT pingchaoli immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT qingyang immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT xiuchangma immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT chunxiuwu immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT jinzhao immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT hongbinyan immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT ruleichen immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT lingchen immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT lingchen immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT caijunsun immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys AT caijunsun immuneprotectionofsivchallengebypd1blockadeduringvaccinationinrhesusmonkeys |