Cargando…

Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant

Protein or peptide-based subunit vaccines have generated excitement and renewed interest in combating human cancer or COVID-19 outbreak. One major concern for subunit vaccine application is the weak immune responses induced by protein or peptides. Developing novel and effective vaccine adjuvants are...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Ning, Garcia, Aitor, Meyer, Cindy, Tuschl, Thomas, Merghoub, Taha, Wolchok, Jedd D., Deng, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580433/
https://www.ncbi.nlm.nih.gov/pubmed/36261460
http://dx.doi.org/10.1038/s41541-022-00542-5
_version_ 1784812383316738048
author Yang, Ning
Garcia, Aitor
Meyer, Cindy
Tuschl, Thomas
Merghoub, Taha
Wolchok, Jedd D.
Deng, Liang
author_facet Yang, Ning
Garcia, Aitor
Meyer, Cindy
Tuschl, Thomas
Merghoub, Taha
Wolchok, Jedd D.
Deng, Liang
author_sort Yang, Ning
collection PubMed
description Protein or peptide-based subunit vaccines have generated excitement and renewed interest in combating human cancer or COVID-19 outbreak. One major concern for subunit vaccine application is the weak immune responses induced by protein or peptides. Developing novel and effective vaccine adjuvants are critical for the success of subunit vaccines. Here we explored the potential of heat-inactivated MVA (heat-iMVA) as a vaccine adjuvant. Heat-iMVA dramatically enhances T cell responses and antibodies responses, mainly toward Th1 immune responses when combined with protein or peptide-based immunogen. The adjuvant effect of Heat-iMVA is stronger than live MVA and is dependent on the cGAS/STING-mediated cytosolic DNA-sensing pathway. In a therapeutic vaccination model based on tumor neoantigen peptide vaccine, Heat-iMVA significantly extended the survival and delayed tumor growth. When combined with SARS-CoV-2 spike protein, Heat-iMVA induced more robust spike-specific antibody production and more potent neutralization antibodies. Our results support that Heat-iMVA can be developed as a safe and potent vaccine adjuvant for subunit vaccines against cancer or SARS-CoV-2.
format Online
Article
Text
id pubmed-9580433
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-95804332022-10-19 Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant Yang, Ning Garcia, Aitor Meyer, Cindy Tuschl, Thomas Merghoub, Taha Wolchok, Jedd D. Deng, Liang NPJ Vaccines Article Protein or peptide-based subunit vaccines have generated excitement and renewed interest in combating human cancer or COVID-19 outbreak. One major concern for subunit vaccine application is the weak immune responses induced by protein or peptides. Developing novel and effective vaccine adjuvants are critical for the success of subunit vaccines. Here we explored the potential of heat-inactivated MVA (heat-iMVA) as a vaccine adjuvant. Heat-iMVA dramatically enhances T cell responses and antibodies responses, mainly toward Th1 immune responses when combined with protein or peptide-based immunogen. The adjuvant effect of Heat-iMVA is stronger than live MVA and is dependent on the cGAS/STING-mediated cytosolic DNA-sensing pathway. In a therapeutic vaccination model based on tumor neoantigen peptide vaccine, Heat-iMVA significantly extended the survival and delayed tumor growth. When combined with SARS-CoV-2 spike protein, Heat-iMVA induced more robust spike-specific antibody production and more potent neutralization antibodies. Our results support that Heat-iMVA can be developed as a safe and potent vaccine adjuvant for subunit vaccines against cancer or SARS-CoV-2. Nature Publishing Group UK 2022-10-19 /pmc/articles/PMC9580433/ /pubmed/36261460 http://dx.doi.org/10.1038/s41541-022-00542-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yang, Ning
Garcia, Aitor
Meyer, Cindy
Tuschl, Thomas
Merghoub, Taha
Wolchok, Jedd D.
Deng, Liang
Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant
title Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant
title_full Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant
title_fullStr Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant
title_full_unstemmed Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant
title_short Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant
title_sort heat-inactivated modified vaccinia virus ankara boosts th1 cellular and humoral immunity as a vaccine adjuvant
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580433/
https://www.ncbi.nlm.nih.gov/pubmed/36261460
http://dx.doi.org/10.1038/s41541-022-00542-5
work_keys_str_mv AT yangning heatinactivatedmodifiedvacciniavirusankarabooststh1cellularandhumoralimmunityasavaccineadjuvant
AT garciaaitor heatinactivatedmodifiedvacciniavirusankarabooststh1cellularandhumoralimmunityasavaccineadjuvant
AT meyercindy heatinactivatedmodifiedvacciniavirusankarabooststh1cellularandhumoralimmunityasavaccineadjuvant
AT tuschlthomas heatinactivatedmodifiedvacciniavirusankarabooststh1cellularandhumoralimmunityasavaccineadjuvant
AT merghoubtaha heatinactivatedmodifiedvacciniavirusankarabooststh1cellularandhumoralimmunityasavaccineadjuvant
AT wolchokjeddd heatinactivatedmodifiedvacciniavirusankarabooststh1cellularandhumoralimmunityasavaccineadjuvant
AT dengliang heatinactivatedmodifiedvacciniavirusankarabooststh1cellularandhumoralimmunityasavaccineadjuvant