Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice

In spring 2013, human infections with a novel avian influenza A (H7N9) virus were reported in China. The number of cases has increased with over 200 mortalities reported to date. However, there is currently no vaccine available for the H7 subtype of influenza A virus. Virus-specific cellular immune...

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Main Authors:	Song, Li, Xiong, Dan, Hu, Maozhi, Kang, Xilong, Pan, Zhiming, Jiao, Xinan
Format:	Online
Language:	English
Published:	Public Library of Science 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773109/

id	pubmed-4773109
recordtype	oai_dc
spelling	pubmed-47731092016-03-07 Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice Song, Li Xiong, Dan Hu, Maozhi Kang, Xilong Pan, Zhiming Jiao, Xinan Research Article In spring 2013, human infections with a novel avian influenza A (H7N9) virus were reported in China. The number of cases has increased with over 200 mortalities reported to date. However, there is currently no vaccine available for the H7 subtype of influenza A virus. Virus-specific cellular immune responses play a critical role in virus clearance during influenza infection. In this study, we undertook a side-by-side evaluation of two different adjuvants, Salmonella typhimurium flagellin (fliC) and polyethyleneimine (PEI), through intraperitoneal administration to assess their effects on the immunogenicity of the recombinant HA1-2 subunit vaccine of H7N9 influenza. The fusion protein HA1-2-fliC and HA1-2 combined with PEI could induce significantly higher HA1-2-specific IgG and hemagglutination inhibition titers than HA1-2 alone at 12 days post-boost, with superior HA1-2 specific IgG titers in the HA1-2-fliC group compared with the PEI adjuvanted group. The PEI adjuvanted vaccine induced higher IgG1/IgG2a ratio and significantly increased numbers of IFN-γ- and IL-4-producing cells than HA1-2 alone, suggesting a mixed Th1/Th2-type cellular immune response with a Th2 bias. Meanwhile, the HA1-2-fliC induced higher IgG2a and IgG1 levels, which is indicative of a mixed Th1/Th2-type profile. Consistent with this, significant levels, and equal numbers, of IFN-γ- and IL-4-producing cells were detected after HA1-2-fliC vaccination. Moreover, the marked increase in CD69 expression and the proliferative index with the HA1-2-fliC and PEI adjuvanted vaccines indicated that both adjuvanted vaccine candidates effectively induced antigen-specific cellular immune responses. Taken together, our findings indicate that the two adjuvanted vaccine candidates elicit effective and HA1-2-specific humoral and cellular immune responses, offering significant promise for the development of a successful recombinant HA1-2 subunit vaccine for H7N9 influenza. Public Library of Science 2016-03-01 /pmc/articles/PMC4773109/ /pubmed/26930068 http://dx.doi.org/10.1371/journal.pone.0150678 Text en © 2016 Song et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Song, Li Xiong, Dan Hu, Maozhi Kang, Xilong Pan, Zhiming Jiao, Xinan
spellingShingle	Song, Li Xiong, Dan Hu, Maozhi Kang, Xilong Pan, Zhiming Jiao, Xinan Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice
author_facet	Song, Li Xiong, Dan Hu, Maozhi Kang, Xilong Pan, Zhiming Jiao, Xinan
author_sort	Song, Li
title	Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice
title_short	Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice
title_full	Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice
title_fullStr	Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice
title_full_unstemmed	Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice
title_sort	immunopotentiation of different adjuvants on humoral and cellular immune responses induced by ha1-2 subunit vaccines of h7n9 influenza in mice
description	In spring 2013, human infections with a novel avian influenza A (H7N9) virus were reported in China. The number of cases has increased with over 200 mortalities reported to date. However, there is currently no vaccine available for the H7 subtype of influenza A virus. Virus-specific cellular immune responses play a critical role in virus clearance during influenza infection. In this study, we undertook a side-by-side evaluation of two different adjuvants, Salmonella typhimurium flagellin (fliC) and polyethyleneimine (PEI), through intraperitoneal administration to assess their effects on the immunogenicity of the recombinant HA1-2 subunit vaccine of H7N9 influenza. The fusion protein HA1-2-fliC and HA1-2 combined with PEI could induce significantly higher HA1-2-specific IgG and hemagglutination inhibition titers than HA1-2 alone at 12 days post-boost, with superior HA1-2 specific IgG titers in the HA1-2-fliC group compared with the PEI adjuvanted group. The PEI adjuvanted vaccine induced higher IgG1/IgG2a ratio and significantly increased numbers of IFN-γ- and IL-4-producing cells than HA1-2 alone, suggesting a mixed Th1/Th2-type cellular immune response with a Th2 bias. Meanwhile, the HA1-2-fliC induced higher IgG2a and IgG1 levels, which is indicative of a mixed Th1/Th2-type profile. Consistent with this, significant levels, and equal numbers, of IFN-γ- and IL-4-producing cells were detected after HA1-2-fliC vaccination. Moreover, the marked increase in CD69 expression and the proliferative index with the HA1-2-fliC and PEI adjuvanted vaccines indicated that both adjuvanted vaccine candidates effectively induced antigen-specific cellular immune responses. Taken together, our findings indicate that the two adjuvanted vaccine candidates elicit effective and HA1-2-specific humoral and cellular immune responses, offering significant promise for the development of a successful recombinant HA1-2 subunit vaccine for H7N9 influenza.
publisher	Public Library of Science
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773109/
_version_	1613545524856619008

Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice

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