gB co‐immunization with GP96 enhances pulmonary‐resident CD8 T cells and exerts a long‐term defence against MCMV pneumonitis
Human cytomegalovirus (HCMV) infection in the respiratory tract leads to pneumonitis in immunocompromised hosts without available vaccine. Considering cytomegalovirus (CMV) mainly invades through the respiratory tract, CMV‐specific pulmonary mucosal vaccine development that provides a long‐lasting p...
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| Veröffentlicht in: | Journal of cellular and molecular medicine 2020-12, Vol.24 (24), p.14426-14440 |
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| creator | Guo, Bingnan Xu, Peifeng Chai, Dafei Cao, Lei Liu, Lin Song, Tengfei Hu, Shuqun Chen, Yuling Yan, Xianliang Xu, Tie |
| description | Human cytomegalovirus (HCMV) infection in the respiratory tract leads to pneumonitis in immunocompromised hosts without available vaccine. Considering cytomegalovirus (CMV) mainly invades through the respiratory tract, CMV‐specific pulmonary mucosal vaccine development that provides a long‐lasting protection against CMV challenge gains our attention. In this study, N‐terminal domain of GP96 (GP96‐NT) was used as a mucosal adjuvant to enhance the induction of pulmonary‐resident CD8 T cells elicited by MCMV glycoprotein B (gB) vaccine. Mice were intranasally co‐immunized with 50 μg pgB and equal amount of pGP96‐NT vaccine 4 times at 2‐week intervals, and then i.n. challenged with MCMV at 16 weeks after the last immunization. Compared with pgB immunization alone, co‐immunization with pgB/pGP96‐NT enhanced a long‐lasting protection against MCMV pneumonitis by significantly improved pneumonitis pathology, enhanced bodyweight, reduced viral burdens and increased survival rate. Moreover, the increased CD8 T cells were observed in lung but not spleen from pgB/pGP96‐NT co‐immunized mice. The increments of pulmonary CD8 T cells might be mainly due to non‐circulating pulmonary‐resident CD8 T‐cell subset expansion but not circulating CD8 T‐cell populations that home to inflammation site upon MCMV challenge. Finally, the deterioration of MCMV pneumonitis by depletion of pulmonary site‐specific CD8 T cells in mice that were pgB/pGP96‐NT co‐immunization might be a clue to interpret the non‐circulating pulmonary‐resident CD8 T subset expansion. These data might uncover a promising long‐lasting prophylactic vaccine strategy against MCMV‐induced pneumonitis. |
| doi_str_mv | 10.1111/jcmm.16065 |
| format | Article |
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Considering cytomegalovirus (CMV) mainly invades through the respiratory tract, CMV‐specific pulmonary mucosal vaccine development that provides a long‐lasting protection against CMV challenge gains our attention. In this study, N‐terminal domain of GP96 (GP96‐NT) was used as a mucosal adjuvant to enhance the induction of pulmonary‐resident CD8 T cells elicited by MCMV glycoprotein B (gB) vaccine. Mice were intranasally co‐immunized with 50 μg pgB and equal amount of pGP96‐NT vaccine 4 times at 2‐week intervals, and then i.n. challenged with MCMV at 16 weeks after the last immunization. Compared with pgB immunization alone, co‐immunization with pgB/pGP96‐NT enhanced a long‐lasting protection against MCMV pneumonitis by significantly improved pneumonitis pathology, enhanced bodyweight, reduced viral burdens and increased survival rate. Moreover, the increased CD8 T cells were observed in lung but not spleen from pgB/pGP96‐NT co‐immunized mice. The increments of pulmonary CD8 T cells might be mainly due to non‐circulating pulmonary‐resident CD8 T‐cell subset expansion but not circulating CD8 T‐cell populations that home to inflammation site upon MCMV challenge. Finally, the deterioration of MCMV pneumonitis by depletion of pulmonary site‐specific CD8 T cells in mice that were pgB/pGP96‐NT co‐immunization might be a clue to interpret the non‐circulating pulmonary‐resident CD8 T subset expansion. These data might uncover a promising long‐lasting prophylactic vaccine strategy against MCMV‐induced pneumonitis.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.16065</identifier><identifier>PMID: 33155438</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Adjuvants ; Administration, Intranasal ; Animals ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Cell Line ; Cytomegalovirus ; Cytomegalovirus - immunology ; Cytomegalovirus Infections - immunology ; Cytomegalovirus Infections - virology ; Deoxyribonucleic acid ; Disease Models, Animal ; DNA ; DNA vaccine ; Female ; Gene expression ; Glycoprotein B ; Glycoprotein gp96 ; GP96 ; Host-Pathogen Interactions ; Humans ; Immunization ; Immunocompromised hosts ; Immunologic Memory ; Infections ; Laboratory animals ; Lung - immunology ; Lung - pathology ; Lymphocyte Activation - immunology ; Lymphocytes ; Lymphocytes T ; Medical research ; Mice ; Mucosa ; Original ; Pathogens ; Plasmids ; Plasmids - genetics ; Pneumonia - immunology ; Pneumonia - virology ; Pneumonitis ; pulmonary‐resident CD8 T cell ; Respiration ; Respiratory tract diseases ; Spleen ; Spleen - immunology ; Spleen - pathology ; Vaccination ; Vaccine development ; Vaccines ; Vaccines, DNA - immunology ; Viral Proteins - immunology ; Viral Vaccines - immunology ; Virulence</subject><ispartof>Journal of cellular and molecular medicine, 2020-12, Vol.24 (24), p.14426-14440</ispartof><rights>2020 The Authors. published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). 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Considering cytomegalovirus (CMV) mainly invades through the respiratory tract, CMV‐specific pulmonary mucosal vaccine development that provides a long‐lasting protection against CMV challenge gains our attention. In this study, N‐terminal domain of GP96 (GP96‐NT) was used as a mucosal adjuvant to enhance the induction of pulmonary‐resident CD8 T cells elicited by MCMV glycoprotein B (gB) vaccine. Mice were intranasally co‐immunized with 50 μg pgB and equal amount of pGP96‐NT vaccine 4 times at 2‐week intervals, and then i.n. challenged with MCMV at 16 weeks after the last immunization. Compared with pgB immunization alone, co‐immunization with pgB/pGP96‐NT enhanced a long‐lasting protection against MCMV pneumonitis by significantly improved pneumonitis pathology, enhanced bodyweight, reduced viral burdens and increased survival rate. Moreover, the increased CD8 T cells were observed in lung but not spleen from pgB/pGP96‐NT co‐immunized mice. The increments of pulmonary CD8 T cells might be mainly due to non‐circulating pulmonary‐resident CD8 T‐cell subset expansion but not circulating CD8 T‐cell populations that home to inflammation site upon MCMV challenge. Finally, the deterioration of MCMV pneumonitis by depletion of pulmonary site‐specific CD8 T cells in mice that were pgB/pGP96‐NT co‐immunization might be a clue to interpret the non‐circulating pulmonary‐resident CD8 T subset expansion. These data might uncover a promising long‐lasting prophylactic vaccine strategy against MCMV‐induced pneumonitis.</description><subject>Adjuvants</subject><subject>Administration, Intranasal</subject><subject>Animals</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Cell Line</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus - immunology</subject><subject>Cytomegalovirus Infections - immunology</subject><subject>Cytomegalovirus Infections - virology</subject><subject>Deoxyribonucleic acid</subject><subject>Disease Models, Animal</subject><subject>DNA</subject><subject>DNA vaccine</subject><subject>Female</subject><subject>Gene expression</subject><subject>Glycoprotein B</subject><subject>Glycoprotein gp96</subject><subject>GP96</subject><subject>Host-Pathogen Interactions</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunocompromised hosts</subject><subject>Immunologic Memory</subject><subject>Infections</subject><subject>Laboratory animals</subject><subject>Lung - 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immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Cell Line</topic><topic>Cytomegalovirus</topic><topic>Cytomegalovirus - immunology</topic><topic>Cytomegalovirus Infections - immunology</topic><topic>Cytomegalovirus Infections - virology</topic><topic>Deoxyribonucleic acid</topic><topic>Disease Models, Animal</topic><topic>DNA</topic><topic>DNA vaccine</topic><topic>Female</topic><topic>Gene expression</topic><topic>Glycoprotein B</topic><topic>Glycoprotein gp96</topic><topic>GP96</topic><topic>Host-Pathogen Interactions</topic><topic>Humans</topic><topic>Immunization</topic><topic>Immunocompromised hosts</topic><topic>Immunologic Memory</topic><topic>Infections</topic><topic>Laboratory animals</topic><topic>Lung - immunology</topic><topic>Lung - pathology</topic><topic>Lymphocyte Activation - immunology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medical research</topic><topic>Mice</topic><topic>Mucosa</topic><topic>Original</topic><topic>Pathogens</topic><topic>Plasmids</topic><topic>Plasmids - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Bingnan</au><au>Xu, Peifeng</au><au>Chai, Dafei</au><au>Cao, Lei</au><au>Liu, Lin</au><au>Song, Tengfei</au><au>Hu, Shuqun</au><au>Chen, Yuling</au><au>Yan, Xianliang</au><au>Xu, Tie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>gB co‐immunization with GP96 enhances pulmonary‐resident CD8 T cells and exerts a long‐term defence against MCMV pneumonitis</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2020-12</date><risdate>2020</risdate><volume>24</volume><issue>24</issue><spage>14426</spage><epage>14440</epage><pages>14426-14440</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Human cytomegalovirus (HCMV) infection in the respiratory tract leads to pneumonitis in immunocompromised hosts without available vaccine. Considering cytomegalovirus (CMV) mainly invades through the respiratory tract, CMV‐specific pulmonary mucosal vaccine development that provides a long‐lasting protection against CMV challenge gains our attention. In this study, N‐terminal domain of GP96 (GP96‐NT) was used as a mucosal adjuvant to enhance the induction of pulmonary‐resident CD8 T cells elicited by MCMV glycoprotein B (gB) vaccine. Mice were intranasally co‐immunized with 50 μg pgB and equal amount of pGP96‐NT vaccine 4 times at 2‐week intervals, and then i.n. challenged with MCMV at 16 weeks after the last immunization. Compared with pgB immunization alone, co‐immunization with pgB/pGP96‐NT enhanced a long‐lasting protection against MCMV pneumonitis by significantly improved pneumonitis pathology, enhanced bodyweight, reduced viral burdens and increased survival rate. Moreover, the increased CD8 T cells were observed in lung but not spleen from pgB/pGP96‐NT co‐immunized mice. The increments of pulmonary CD8 T cells might be mainly due to non‐circulating pulmonary‐resident CD8 T‐cell subset expansion but not circulating CD8 T‐cell populations that home to inflammation site upon MCMV challenge. Finally, the deterioration of MCMV pneumonitis by depletion of pulmonary site‐specific CD8 T cells in mice that were pgB/pGP96‐NT co‐immunization might be a clue to interpret the non‐circulating pulmonary‐resident CD8 T subset expansion. These data might uncover a promising long‐lasting prophylactic vaccine strategy against MCMV‐induced pneumonitis.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>33155438</pmid><doi>10.1111/jcmm.16065</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-5155-5319</orcidid><orcidid>https://orcid.org/0000-0002-1148-7155</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of cellular and molecular medicine, 2020-12, Vol.24 (24), p.14426-14440 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals; Wiley Online Library (Open Access Collection); PubMed Central |
| subjects | Adjuvants Administration, Intranasal Animals CD8 antigen CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell Line Cytomegalovirus Cytomegalovirus - immunology Cytomegalovirus Infections - immunology Cytomegalovirus Infections - virology Deoxyribonucleic acid Disease Models, Animal DNA DNA vaccine Female Gene expression Glycoprotein B Glycoprotein gp96 GP96 Host-Pathogen Interactions Humans Immunization Immunocompromised hosts Immunologic Memory Infections Laboratory animals Lung - immunology Lung - pathology Lymphocyte Activation - immunology Lymphocytes Lymphocytes T Medical research Mice Mucosa Original Pathogens Plasmids Plasmids - genetics Pneumonia - immunology Pneumonia - virology Pneumonitis pulmonary‐resident CD8 T cell Respiration Respiratory tract diseases Spleen Spleen - immunology Spleen - pathology Vaccination Vaccine development Vaccines Vaccines, DNA - immunology Viral Proteins - immunology Viral Vaccines - immunology Virulence |
| title | gB co‐immunization with GP96 enhances pulmonary‐resident CD8 T cells and exerts a long‐term defence against MCMV pneumonitis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T18%3A04%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=gB%20co%E2%80%90immunization%20with%20GP96%20enhances%20pulmonary%E2%80%90resident%20CD8%20T%20cells%20and%20exerts%20a%20long%E2%80%90term%20defence%20against%20MCMV%20pneumonitis&rft.jtitle=Journal%20of%20cellular%20and%20molecular%20medicine&rft.au=Guo,%20Bingnan&rft.date=2020-12&rft.volume=24&rft.issue=24&rft.spage=14426&rft.epage=14440&rft.pages=14426-14440&rft.issn=1582-1838&rft.eissn=1582-4934&rft_id=info:doi/10.1111/jcmm.16065&rft_dat=%3Cproquest_pubme%3E3090169857%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2467800305&rft_id=info:pmid/33155438&rfr_iscdi=true |