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CpG 1018 Is an Effective Adjuvant for Influenza Nucleoprotein

Current influenza vaccines mainly induce neutralizing antibodies against the highly variable surface antigen hemagglutinin and require annual manufacturing and immunization. Different from surface antigens, intracellular nucleoprotein (NP) is highly conserved and has been an attractive target to dev...

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Autores principales: Li, Yibo, Chen, Xinyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055716/
https://www.ncbi.nlm.nih.gov/pubmed/36992232
http://dx.doi.org/10.3390/vaccines11030649
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author Li, Yibo
Chen, Xinyuan
author_facet Li, Yibo
Chen, Xinyuan
author_sort Li, Yibo
collection PubMed
description Current influenza vaccines mainly induce neutralizing antibodies against the highly variable surface antigen hemagglutinin and require annual manufacturing and immunization. Different from surface antigens, intracellular nucleoprotein (NP) is highly conserved and has been an attractive target to develop universal T cell vaccines against influenza. Yet, influenza NP protein mainly induces humoral immune responses and lacks the ability to induce potent cytotoxic T lymphocyte (CTL) responses, key for the success of universal T cell vaccines. This study compared CpG 1018 and AddaVax to enhance recombinant NP-induced CTL responses and protection in murine models. CpG 1018 was explored to boost intradermal NP immunization, while AddaVax was explored to boost intramuscular NP immunization due to the high risk of AddaVax adjuvant to induce significant local reactions following intradermal delivery. We found CpG 1018 was highly effective to enhance NP-induced humoral and cellular immune responses superior to AddaVax adjuvant. Furthermore, CpG 1018 potentiated Th1-biased antibody responses, while AddaVax enhanced Th1/Th2-balanced antibody responses. CpG 1018 significantly enhanced IFNγ-secreting Th1 cells, while AddaVax adjuvant significantly increased IL4-secreting Th2 cells. Influenza NP immunization in the presence of CpG 1018 induced significant protection against lethal viral challenges, while influenza NP immunization in the presence of AddaVax failed to elicit significant protection. Our data validated CpG 1018 as an effective adjuvant to enhance influenza NP-induced CTL responses and protection.
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spelling pubmed-100557162023-03-30 CpG 1018 Is an Effective Adjuvant for Influenza Nucleoprotein Li, Yibo Chen, Xinyuan Vaccines (Basel) Article Current influenza vaccines mainly induce neutralizing antibodies against the highly variable surface antigen hemagglutinin and require annual manufacturing and immunization. Different from surface antigens, intracellular nucleoprotein (NP) is highly conserved and has been an attractive target to develop universal T cell vaccines against influenza. Yet, influenza NP protein mainly induces humoral immune responses and lacks the ability to induce potent cytotoxic T lymphocyte (CTL) responses, key for the success of universal T cell vaccines. This study compared CpG 1018 and AddaVax to enhance recombinant NP-induced CTL responses and protection in murine models. CpG 1018 was explored to boost intradermal NP immunization, while AddaVax was explored to boost intramuscular NP immunization due to the high risk of AddaVax adjuvant to induce significant local reactions following intradermal delivery. We found CpG 1018 was highly effective to enhance NP-induced humoral and cellular immune responses superior to AddaVax adjuvant. Furthermore, CpG 1018 potentiated Th1-biased antibody responses, while AddaVax enhanced Th1/Th2-balanced antibody responses. CpG 1018 significantly enhanced IFNγ-secreting Th1 cells, while AddaVax adjuvant significantly increased IL4-secreting Th2 cells. Influenza NP immunization in the presence of CpG 1018 induced significant protection against lethal viral challenges, while influenza NP immunization in the presence of AddaVax failed to elicit significant protection. Our data validated CpG 1018 as an effective adjuvant to enhance influenza NP-induced CTL responses and protection. MDPI 2023-03-14 /pmc/articles/PMC10055716/ /pubmed/36992232 http://dx.doi.org/10.3390/vaccines11030649 Text en © 2023 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
Chen, Xinyuan
CpG 1018 Is an Effective Adjuvant for Influenza Nucleoprotein
title CpG 1018 Is an Effective Adjuvant for Influenza Nucleoprotein
title_full CpG 1018 Is an Effective Adjuvant for Influenza Nucleoprotein
title_fullStr CpG 1018 Is an Effective Adjuvant for Influenza Nucleoprotein
title_full_unstemmed CpG 1018 Is an Effective Adjuvant for Influenza Nucleoprotein
title_short CpG 1018 Is an Effective Adjuvant for Influenza Nucleoprotein
title_sort cpg 1018 is an effective adjuvant for influenza nucleoprotein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055716/
https://www.ncbi.nlm.nih.gov/pubmed/36992232
http://dx.doi.org/10.3390/vaccines11030649
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