Cargando…

Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine

We previously identified Alcaligenes spp. as a commensal bacterium that resides in lymphoid tissues, including Peyer’s patches. We found that Alcaligenes-derived lipopolysaccharide acted as a weak agonist of Toll-like receptor four due to the unique structure of lipid A, which lies in the core of li...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Zilai, Hosomi, Koji, Shimoyama, Atsushi, Yoshii, Ken, Sun, Xiao, Lan, Huangwenxian, Wang, Yunru, Yamaura, Haruki, Kenneth, Davie, Saika, Azusa, Nagatake, Takahiro, Kiyono, Hiroshi, Fukase, Koichi, Kunisawa, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569242/
https://www.ncbi.nlm.nih.gov/pubmed/34744743
http://dx.doi.org/10.3389/fphar.2021.763657
_version_ 1784594612184154112
author Liu, Zilai
Hosomi, Koji
Shimoyama, Atsushi
Yoshii, Ken
Sun, Xiao
Lan, Huangwenxian
Wang, Yunru
Yamaura, Haruki
Kenneth, Davie
Saika, Azusa
Nagatake, Takahiro
Kiyono, Hiroshi
Fukase, Koichi
Kunisawa, Jun
author_facet Liu, Zilai
Hosomi, Koji
Shimoyama, Atsushi
Yoshii, Ken
Sun, Xiao
Lan, Huangwenxian
Wang, Yunru
Yamaura, Haruki
Kenneth, Davie
Saika, Azusa
Nagatake, Takahiro
Kiyono, Hiroshi
Fukase, Koichi
Kunisawa, Jun
author_sort Liu, Zilai
collection PubMed
description We previously identified Alcaligenes spp. as a commensal bacterium that resides in lymphoid tissues, including Peyer’s patches. We found that Alcaligenes-derived lipopolysaccharide acted as a weak agonist of Toll-like receptor four due to the unique structure of lipid A, which lies in the core of lipopolysaccharide. This feature allowed the use of chemically synthesized Alcaligenes lipid A as a safe synthetic vaccine adjuvant that induces Th17 polarization to enhance systemic IgG and respiratory IgA responses to T-cell–dependent antigens (e.g., ovalbumin and pneumococcal surface protein A) without excessive inflammation. Here, we examined the adjuvant activity of Alcaligenes lipid A on a Haemophilus influenzae B conjugate vaccine that contains capsular polysaccharide polyribosyl ribitol phosphate (PRP), a T-cell–independent antigen, conjugated with the T-cell–dependent tetanus toxoid (TT) antigen (i.e., PRP-TT). When mice were subcutaneously immunized with PRP alone or mixed with TT, Alcaligenes lipid A did not affect PRP-specific IgG production. In contrast, PRP-specific serum IgG responses were enhanced when mice were immunized with PRP-TT, but these responses were impaired in similarly immunized T-cell—deficient nude mice. Furthermore, TT-specific—but not PRP-specific—T-cell activation occurred in mice immunized with PRP-TT together with Alcaligenes lipid A. In addition, coculture with Alcaligenes lipid A promoted significant proliferation of and enhanced antibody production by B cells. Together, these findings suggest that Alcaligenes lipid A exerts an adjuvant activity on thymus-independent Hib polysaccharide antigen in the presence of a T-cell–dependent conjugate carrier antigen.
format Online
Article
Text
id pubmed-8569242
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-85692422021-11-06 Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine Liu, Zilai Hosomi, Koji Shimoyama, Atsushi Yoshii, Ken Sun, Xiao Lan, Huangwenxian Wang, Yunru Yamaura, Haruki Kenneth, Davie Saika, Azusa Nagatake, Takahiro Kiyono, Hiroshi Fukase, Koichi Kunisawa, Jun Front Pharmacol Pharmacology We previously identified Alcaligenes spp. as a commensal bacterium that resides in lymphoid tissues, including Peyer’s patches. We found that Alcaligenes-derived lipopolysaccharide acted as a weak agonist of Toll-like receptor four due to the unique structure of lipid A, which lies in the core of lipopolysaccharide. This feature allowed the use of chemically synthesized Alcaligenes lipid A as a safe synthetic vaccine adjuvant that induces Th17 polarization to enhance systemic IgG and respiratory IgA responses to T-cell–dependent antigens (e.g., ovalbumin and pneumococcal surface protein A) without excessive inflammation. Here, we examined the adjuvant activity of Alcaligenes lipid A on a Haemophilus influenzae B conjugate vaccine that contains capsular polysaccharide polyribosyl ribitol phosphate (PRP), a T-cell–independent antigen, conjugated with the T-cell–dependent tetanus toxoid (TT) antigen (i.e., PRP-TT). When mice were subcutaneously immunized with PRP alone or mixed with TT, Alcaligenes lipid A did not affect PRP-specific IgG production. In contrast, PRP-specific serum IgG responses were enhanced when mice were immunized with PRP-TT, but these responses were impaired in similarly immunized T-cell—deficient nude mice. Furthermore, TT-specific—but not PRP-specific—T-cell activation occurred in mice immunized with PRP-TT together with Alcaligenes lipid A. In addition, coculture with Alcaligenes lipid A promoted significant proliferation of and enhanced antibody production by B cells. Together, these findings suggest that Alcaligenes lipid A exerts an adjuvant activity on thymus-independent Hib polysaccharide antigen in the presence of a T-cell–dependent conjugate carrier antigen. Frontiers Media S.A. 2021-10-22 /pmc/articles/PMC8569242/ /pubmed/34744743 http://dx.doi.org/10.3389/fphar.2021.763657 Text en Copyright © 2021 Liu, Hosomi, Shimoyama, Yoshii, Sun, Lan, Wang, Yamaura, Kenneth, Saika, Nagatake, Kiyono, Fukase and Kunisawa. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Liu, Zilai
Hosomi, Koji
Shimoyama, Atsushi
Yoshii, Ken
Sun, Xiao
Lan, Huangwenxian
Wang, Yunru
Yamaura, Haruki
Kenneth, Davie
Saika, Azusa
Nagatake, Takahiro
Kiyono, Hiroshi
Fukase, Koichi
Kunisawa, Jun
Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine
title Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine
title_full Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine
title_fullStr Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine
title_full_unstemmed Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine
title_short Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine
title_sort chemically synthesized alcaligenes lipid a as an adjuvant to augment immune responses to haemophilus influenzae type b conjugate vaccine
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569242/
https://www.ncbi.nlm.nih.gov/pubmed/34744743
http://dx.doi.org/10.3389/fphar.2021.763657
work_keys_str_mv AT liuzilai chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT hosomikoji chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT shimoyamaatsushi chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT yoshiiken chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT sunxiao chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT lanhuangwenxian chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT wangyunru chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT yamauraharuki chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT kennethdavie chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT saikaazusa chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT nagataketakahiro chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT kiyonohiroshi chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT fukasekoichi chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine
AT kunisawajun chemicallysynthesizedalcaligeneslipidaasanadjuvanttoaugmentimmuneresponsestohaemophilusinfluenzaetypebconjugatevaccine