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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...

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Autores principales: Li, Yibo, Li, Zhuofan, Zhao, Yiwen, Chen, Xinyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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