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Immune Responses to HBsAg Conjugated to Protein D of Non-Typeable Haemophilus influenzae in Mice
BACKGROUND: Hepatitis B vaccine that contains an aluminum hydroxide adjuvant induces apoptotic death of Hepa 1–6 cells. Difficult-to-degrade chemical additives in vaccines effectively enhance vaccine immunogenicity, but also affect the host tissue. Identification of bio-molecules that are readily de...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331537/ https://www.ncbi.nlm.nih.gov/pubmed/25689855 http://dx.doi.org/10.1371/journal.pone.0117736 |
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author | Su, Qiudong Yi, Yao Qiu, Feng Lu, Xuexin Ding, Junying Jia, Zhiyuan Tian, Ruiguang Gao, Yan Bi, Shengli |
author_facet | Su, Qiudong Yi, Yao Qiu, Feng Lu, Xuexin Ding, Junying Jia, Zhiyuan Tian, Ruiguang Gao, Yan Bi, Shengli |
author_sort | Su, Qiudong |
collection | PubMed |
description | BACKGROUND: Hepatitis B vaccine that contains an aluminum hydroxide adjuvant induces apoptotic death of Hepa 1–6 cells. Difficult-to-degrade chemical additives in vaccines effectively enhance vaccine immunogenicity, but also affect the host tissue. Identification of bio-molecules that are readily degraded and compatible in vivo as an adjuvant is important for vaccine research. The hapten–carrier effect suggests that stimulation of helper T (Th) cells by carrier adjuvants is feasible. Protein D (PD) of non-typeable Haemophilus influenzae covalently conjugated to some polysaccharide vaccines has been confirmed to convert T-cell independent (TI) antigens into T-cell dependent (TD) antigens, and elicit strong T-cell responses ultimately. Herein, we would substitube PD for aluminum hydroxide adjuvant in Hepatitis B vaccine. METHODS AND RESULTS: Truncated PD (amino acids 20–364) was expressed in Escherichia coli and purified by (NH(4))(2)SO(4) precipitation and DEAE chromatography. After evaluation of antigenicity by western blotting, PD was covalently conjugated to yeast-derived recombinant HBsAg by cross-linking with glutaraldehyde. Intramuscular immunization with the conjugate induced higher level of HBsAg-specific antibody than did HBsAg alone (p < 0.05), and was comparable to commercial Hepatitis B vaccine. During the surveillance period (days 35–105), anti-HBs titers were hold high. Moreover, the conjugated vaccine enhanced Th1 immune responses, while Th2 responses were also activated and induced an antibody response, as determined by IFN-γ ELISPOT and IgG1/IgG2a ratio assays. CONCLUSIONS: Recombinant truncated PD covalently conjugated to HBsAg antigen enhanced the immunogenicity of the antigen in mice simultaneously by humoral and cellular immune response, which would facilitate therapeutic hepatitis B vaccines. |
format | Online Article Text |
id | pubmed-4331537 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43315372015-02-24 Immune Responses to HBsAg Conjugated to Protein D of Non-Typeable Haemophilus influenzae in Mice Su, Qiudong Yi, Yao Qiu, Feng Lu, Xuexin Ding, Junying Jia, Zhiyuan Tian, Ruiguang Gao, Yan Bi, Shengli PLoS One Research Article BACKGROUND: Hepatitis B vaccine that contains an aluminum hydroxide adjuvant induces apoptotic death of Hepa 1–6 cells. Difficult-to-degrade chemical additives in vaccines effectively enhance vaccine immunogenicity, but also affect the host tissue. Identification of bio-molecules that are readily degraded and compatible in vivo as an adjuvant is important for vaccine research. The hapten–carrier effect suggests that stimulation of helper T (Th) cells by carrier adjuvants is feasible. Protein D (PD) of non-typeable Haemophilus influenzae covalently conjugated to some polysaccharide vaccines has been confirmed to convert T-cell independent (TI) antigens into T-cell dependent (TD) antigens, and elicit strong T-cell responses ultimately. Herein, we would substitube PD for aluminum hydroxide adjuvant in Hepatitis B vaccine. METHODS AND RESULTS: Truncated PD (amino acids 20–364) was expressed in Escherichia coli and purified by (NH(4))(2)SO(4) precipitation and DEAE chromatography. After evaluation of antigenicity by western blotting, PD was covalently conjugated to yeast-derived recombinant HBsAg by cross-linking with glutaraldehyde. Intramuscular immunization with the conjugate induced higher level of HBsAg-specific antibody than did HBsAg alone (p < 0.05), and was comparable to commercial Hepatitis B vaccine. During the surveillance period (days 35–105), anti-HBs titers were hold high. Moreover, the conjugated vaccine enhanced Th1 immune responses, while Th2 responses were also activated and induced an antibody response, as determined by IFN-γ ELISPOT and IgG1/IgG2a ratio assays. CONCLUSIONS: Recombinant truncated PD covalently conjugated to HBsAg antigen enhanced the immunogenicity of the antigen in mice simultaneously by humoral and cellular immune response, which would facilitate therapeutic hepatitis B vaccines. Public Library of Science 2015-02-17 /pmc/articles/PMC4331537/ /pubmed/25689855 http://dx.doi.org/10.1371/journal.pone.0117736 Text en © 2015 Su 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Su, Qiudong Yi, Yao Qiu, Feng Lu, Xuexin Ding, Junying Jia, Zhiyuan Tian, Ruiguang Gao, Yan Bi, Shengli Immune Responses to HBsAg Conjugated to Protein D of Non-Typeable Haemophilus influenzae in Mice |
title | Immune Responses to HBsAg Conjugated to Protein D of Non-Typeable Haemophilus influenzae in Mice |
title_full | Immune Responses to HBsAg Conjugated to Protein D of Non-Typeable Haemophilus influenzae in Mice |
title_fullStr | Immune Responses to HBsAg Conjugated to Protein D of Non-Typeable Haemophilus influenzae in Mice |
title_full_unstemmed | Immune Responses to HBsAg Conjugated to Protein D of Non-Typeable Haemophilus influenzae in Mice |
title_short | Immune Responses to HBsAg Conjugated to Protein D of Non-Typeable Haemophilus influenzae in Mice |
title_sort | immune responses to hbsag conjugated to protein d of non-typeable haemophilus influenzae in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331537/ https://www.ncbi.nlm.nih.gov/pubmed/25689855 http://dx.doi.org/10.1371/journal.pone.0117736 |
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