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cGAMP-adjuvanted multivalent influenza mRNA vaccines induce broadly protective immunity through cutaneous vaccination in mice

Increasing preclinical and clinical results have demonstrated that mRNA vaccines efficiently prevent infectious diseases and are safe in animal models and humans. In this study, we fabricated a multivalent influenza mRNA lipid nanoparticle (LNP) vaccine with mRNAs of hemagglutinins from influenza H1...

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Autores principales: Zhu, Wandi, Wei, Lai, Dong, Chunhong, Wang, Ye, Kim, Joo, Ma, Yao, Gonzalez, Gilbert X., Wang, Bao-Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668623/
https://www.ncbi.nlm.nih.gov/pubmed/36420215
http://dx.doi.org/10.1016/j.omtn.2022.10.024
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author Zhu, Wandi
Wei, Lai
Dong, Chunhong
Wang, Ye
Kim, Joo
Ma, Yao
Gonzalez, Gilbert X.
Wang, Bao-Zhong
author_facet Zhu, Wandi
Wei, Lai
Dong, Chunhong
Wang, Ye
Kim, Joo
Ma, Yao
Gonzalez, Gilbert X.
Wang, Bao-Zhong
author_sort Zhu, Wandi
collection PubMed
description Increasing preclinical and clinical results have demonstrated that mRNA vaccines efficiently prevent infectious diseases and are safe in animal models and humans. In this study, we fabricated a multivalent influenza mRNA lipid nanoparticle (LNP) vaccine with mRNAs of hemagglutinins from influenza H1N1 and H3N2 viruses, matrix protein 1, and nucleoprotein. We found that cutaneous immunization with mRNA LNPs induced strong Th1 and Th2 cellular immunity with robust antigen-specific antibody titers and increased cytokine-secreting splenocytes and antibody-secreting cells. The supplement of cGAMP improved the immunogenicity of mRNA LNPs. Compared with αGC or cGAMP/αGC adjuvanted mRNA LNP formulations in our study, cGAMP mRNA LNPs induced more robust antibody responses. Enhanced cellular immunity with more IL-4 and IFN-γ secreting cells and effector memory T cell populations in spleens, as well as increased CD4+ resident memory (T(RM)) T cells in lungs were observed in cGAMP mRNA LNPs immunized group. These results demonstrated that cGAMP is an effective adjuvant for cutaneous vaccination of multivalent mRNA LNP vaccines in mice to induce stronger immune responses in the spleen and lung, and the cGAMP-adjuvanted mRNA LNPs protected against homologous and heterologous viral infection.
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spelling pubmed-96686232022-11-22 cGAMP-adjuvanted multivalent influenza mRNA vaccines induce broadly protective immunity through cutaneous vaccination in mice Zhu, Wandi Wei, Lai Dong, Chunhong Wang, Ye Kim, Joo Ma, Yao Gonzalez, Gilbert X. Wang, Bao-Zhong Mol Ther Nucleic Acids Original Article Increasing preclinical and clinical results have demonstrated that mRNA vaccines efficiently prevent infectious diseases and are safe in animal models and humans. In this study, we fabricated a multivalent influenza mRNA lipid nanoparticle (LNP) vaccine with mRNAs of hemagglutinins from influenza H1N1 and H3N2 viruses, matrix protein 1, and nucleoprotein. We found that cutaneous immunization with mRNA LNPs induced strong Th1 and Th2 cellular immunity with robust antigen-specific antibody titers and increased cytokine-secreting splenocytes and antibody-secreting cells. The supplement of cGAMP improved the immunogenicity of mRNA LNPs. Compared with αGC or cGAMP/αGC adjuvanted mRNA LNP formulations in our study, cGAMP mRNA LNPs induced more robust antibody responses. Enhanced cellular immunity with more IL-4 and IFN-γ secreting cells and effector memory T cell populations in spleens, as well as increased CD4+ resident memory (T(RM)) T cells in lungs were observed in cGAMP mRNA LNPs immunized group. These results demonstrated that cGAMP is an effective adjuvant for cutaneous vaccination of multivalent mRNA LNP vaccines in mice to induce stronger immune responses in the spleen and lung, and the cGAMP-adjuvanted mRNA LNPs protected against homologous and heterologous viral infection. American Society of Gene & Cell Therapy 2022-11-09 /pmc/articles/PMC9668623/ /pubmed/36420215 http://dx.doi.org/10.1016/j.omtn.2022.10.024 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Zhu, Wandi
Wei, Lai
Dong, Chunhong
Wang, Ye
Kim, Joo
Ma, Yao
Gonzalez, Gilbert X.
Wang, Bao-Zhong
cGAMP-adjuvanted multivalent influenza mRNA vaccines induce broadly protective immunity through cutaneous vaccination in mice
title cGAMP-adjuvanted multivalent influenza mRNA vaccines induce broadly protective immunity through cutaneous vaccination in mice
title_full cGAMP-adjuvanted multivalent influenza mRNA vaccines induce broadly protective immunity through cutaneous vaccination in mice
title_fullStr cGAMP-adjuvanted multivalent influenza mRNA vaccines induce broadly protective immunity through cutaneous vaccination in mice
title_full_unstemmed cGAMP-adjuvanted multivalent influenza mRNA vaccines induce broadly protective immunity through cutaneous vaccination in mice
title_short cGAMP-adjuvanted multivalent influenza mRNA vaccines induce broadly protective immunity through cutaneous vaccination in mice
title_sort cgamp-adjuvanted multivalent influenza mrna vaccines induce broadly protective immunity through cutaneous vaccination in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668623/
https://www.ncbi.nlm.nih.gov/pubmed/36420215
http://dx.doi.org/10.1016/j.omtn.2022.10.024
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