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Potentiation of Recombinant NP and M1-Induced Cellular Immune Responses and Protection by Physical Radiofrequency Adjuvant
Nucleoprotein (NP) and matrix protein 1 (M1) are highly conserved among influenza A viruses and have been attractive targets to develop vaccines to elicit cross-reactive cytotoxic T lymphocytes (CTLs). Yet, external antigens are often presented on major histocompatibility complex class II molecules...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706500/ https://www.ncbi.nlm.nih.gov/pubmed/34960128 http://dx.doi.org/10.3390/vaccines9121382 |
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author | Li, Yibo Li, Zhuofan Zhao, Yiwen Chen, Xinyuan |
author_facet | Li, Yibo Li, Zhuofan Zhao, Yiwen Chen, Xinyuan |
author_sort | Li, Yibo |
collection | PubMed |
description | Nucleoprotein (NP) and matrix protein 1 (M1) are highly conserved among influenza A viruses and have been attractive targets to develop vaccines to elicit cross-reactive cytotoxic T lymphocytes (CTLs). Yet, external antigens are often presented on major histocompatibility complex class II molecules and elicit humoral immune responses. In this study, we present a physical radiofrequency adjuvant (RFA) to assist recombinant NP and M1 to elicit potent CTL responses. We found recombinant NP/M1 immunization in the presence of RFA could elicit potent anti-NP CTLs and confer significant protection against homologous viral challenges, while NP/M1 immunization alone failed to elicit significant CTL responses or confer significant protection. Interestingly, RFA failed to elicit potent anti-M1 CTL responses or anti-NP or anti-M1 antibody responses. Different from RFA, AddaVax adjuvant was found to significantly increase NP-specific antibody responses but not CTLs. NP/M1 immunization in the presence of RFA or AddaVax similarly reduced body weight loss, while only the former significantly increased the survival. We further found NP/M1 immunization in the presence of RFA did not significantly increase serum IL-6 release (a systemic inflammatory mediator) and rather reduced serum IL-6 release after boost immunization. NP/M1 immunization in the presence of RFA did not induce significant local reactions or increase body temperature of mice. The high potency and safety strongly support further development of RFA-based recombinant NP/M1 vaccine to elicit cross-protective immunity. |
format | Online Article Text |
id | pubmed-8706500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87065002021-12-25 Potentiation of Recombinant NP and M1-Induced Cellular Immune Responses and Protection by Physical Radiofrequency Adjuvant Li, Yibo Li, Zhuofan Zhao, Yiwen Chen, Xinyuan Vaccines (Basel) Article Nucleoprotein (NP) and matrix protein 1 (M1) are highly conserved among influenza A viruses and have been attractive targets to develop vaccines to elicit cross-reactive cytotoxic T lymphocytes (CTLs). Yet, external antigens are often presented on major histocompatibility complex class II molecules and elicit humoral immune responses. In this study, we present a physical radiofrequency adjuvant (RFA) to assist recombinant NP and M1 to elicit potent CTL responses. We found recombinant NP/M1 immunization in the presence of RFA could elicit potent anti-NP CTLs and confer significant protection against homologous viral challenges, while NP/M1 immunization alone failed to elicit significant CTL responses or confer significant protection. Interestingly, RFA failed to elicit potent anti-M1 CTL responses or anti-NP or anti-M1 antibody responses. Different from RFA, AddaVax adjuvant was found to significantly increase NP-specific antibody responses but not CTLs. NP/M1 immunization in the presence of RFA or AddaVax similarly reduced body weight loss, while only the former significantly increased the survival. We further found NP/M1 immunization in the presence of RFA did not significantly increase serum IL-6 release (a systemic inflammatory mediator) and rather reduced serum IL-6 release after boost immunization. NP/M1 immunization in the presence of RFA did not induce significant local reactions or increase body temperature of mice. The high potency and safety strongly support further development of RFA-based recombinant NP/M1 vaccine to elicit cross-protective immunity. MDPI 2021-11-24 /pmc/articles/PMC8706500/ /pubmed/34960128 http://dx.doi.org/10.3390/vaccines9121382 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Li, Yibo Li, Zhuofan Zhao, Yiwen Chen, Xinyuan Potentiation of Recombinant NP and M1-Induced Cellular Immune Responses and Protection by Physical Radiofrequency Adjuvant |
title | Potentiation of Recombinant NP and M1-Induced Cellular Immune Responses and Protection by Physical Radiofrequency Adjuvant |
title_full | Potentiation of Recombinant NP and M1-Induced Cellular Immune Responses and Protection by Physical Radiofrequency Adjuvant |
title_fullStr | Potentiation of Recombinant NP and M1-Induced Cellular Immune Responses and Protection by Physical Radiofrequency Adjuvant |
title_full_unstemmed | Potentiation of Recombinant NP and M1-Induced Cellular Immune Responses and Protection by Physical Radiofrequency Adjuvant |
title_short | Potentiation of Recombinant NP and M1-Induced Cellular Immune Responses and Protection by Physical Radiofrequency Adjuvant |
title_sort | potentiation of recombinant np and m1-induced cellular immune responses and protection by physical radiofrequency adjuvant |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706500/ https://www.ncbi.nlm.nih.gov/pubmed/34960128 http://dx.doi.org/10.3390/vaccines9121382 |
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