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...
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Frontiers Media S.A.
2021-10-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.763657/full |
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| author | Zilai Liu Zilai Liu Koji Hosomi Atsushi Shimoyama Ken Yoshii Ken Yoshii Xiao Sun Xiao Sun Huangwenxian Lan Huangwenxian Lan Yunru Wang Yunru Wang Haruki Yamaura Davie Kenneth Azusa Saika Azusa Saika Takahiro Nagatake Hiroshi Kiyono Hiroshi Kiyono Hiroshi Kiyono Hiroshi Kiyono Hiroshi Kiyono Koichi Fukase Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa |
| author_facet | Zilai Liu Zilai Liu Koji Hosomi Atsushi Shimoyama Ken Yoshii Ken Yoshii Xiao Sun Xiao Sun Huangwenxian Lan Huangwenxian Lan Yunru Wang Yunru Wang Haruki Yamaura Davie Kenneth Azusa Saika Azusa Saika Takahiro Nagatake Hiroshi Kiyono Hiroshi Kiyono Hiroshi Kiyono Hiroshi Kiyono Hiroshi Kiyono Koichi Fukase Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa |
| author_sort | Zilai Liu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T08:25:00Z |
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| language | English |
| last_indexed | 2024-12-17T08:25:00Z |
| publishDate | 2021-10-01 |
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| spelling | doaj.art-c99821b82a334282b9ac3e1f481b18a02022-12-21T21:56:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-10-011210.3389/fphar.2021.763657763657Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate VaccineZilai Liu0Zilai Liu1Koji Hosomi2Atsushi Shimoyama3Ken Yoshii4Ken Yoshii5Xiao Sun6Xiao Sun7Huangwenxian Lan8Huangwenxian Lan9Yunru Wang10Yunru Wang11Haruki Yamaura12Davie Kenneth13Azusa Saika14Azusa Saika15Takahiro Nagatake16Hiroshi Kiyono17Hiroshi Kiyono18Hiroshi Kiyono19Hiroshi Kiyono20Hiroshi Kiyono21Koichi Fukase22Jun Kunisawa23Jun Kunisawa24Jun Kunisawa25Jun Kunisawa26Jun Kunisawa27Jun Kunisawa28Jun Kunisawa29Jun Kunisawa30Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health, and Nutrition (NIBIOHN), Ibaraki, JapanGraduate School of Pharmaceutical Sciences, Osaka University, Suita, JapanLaboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health, and Nutrition (NIBIOHN), Ibaraki, JapanGraduate School of Science, Osaka University, Toyonaka, JapanLaboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health, and Nutrition (NIBIOHN), Ibaraki, JapanGraduate School of Medicine, Osaka University, Suita, JapanLaboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health, and Nutrition (NIBIOHN), Ibaraki, JapanGraduate School of Pharmaceutical Sciences, Osaka University, Suita, JapanLaboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health, and Nutrition (NIBIOHN), Ibaraki, JapanGraduate School of Pharmaceutical Sciences, Osaka University, Suita, JapanLaboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health, and Nutrition (NIBIOHN), Ibaraki, JapanGraduate School of Pharmaceutical Sciences, Osaka University, Suita, JapanGraduate School of Science, Osaka University, Toyonaka, JapanGraduate School of Science, Osaka University, Toyonaka, JapanLaboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health, and Nutrition (NIBIOHN), Ibaraki, JapanGraduate School of Pharmaceutical Sciences, Osaka University, Suita, JapanLaboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health, and Nutrition (NIBIOHN), Ibaraki, JapanInternational Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, JapanDivision of Gastroenterology, Department of Medicine, University of California San Diego (UCSD), San Diego, CA, United StatesChiba University (CU)-UCSD Center for Mucosal Immunology, Allergy and Vaccines (cMAV), UCSD, San Diego, CA, United StatesFuture Medicine Education and Research Organization, Chiba University, Chiba, JapanDivision of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, JapanGraduate School of Science, Osaka University, Toyonaka, JapanLaboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health, and Nutrition (NIBIOHN), Ibaraki, JapanGraduate School of Pharmaceutical Sciences, Osaka University, Suita, JapanGraduate School of Science, Osaka University, Toyonaka, JapanGraduate School of Medicine, Osaka University, Suita, JapanInternational Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan0Graduate School of Medicine, Kobe University, Kobe, Japan1Research Organization for Nano and Life Innovation, Waseda University, Tokyo, Japan2Graduate School of Dentistry, Osaka University, Suita, JapanWe 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.763657/fullalcaligeneslipid AadjuvantTI antigenhaemophilus influenzae type B |
| spellingShingle | Zilai Liu Zilai Liu Koji Hosomi Atsushi Shimoyama Ken Yoshii Ken Yoshii Xiao Sun Xiao Sun Huangwenxian Lan Huangwenxian Lan Yunru Wang Yunru Wang Haruki Yamaura Davie Kenneth Azusa Saika Azusa Saika Takahiro Nagatake Hiroshi Kiyono Hiroshi Kiyono Hiroshi Kiyono Hiroshi Kiyono Hiroshi Kiyono Koichi Fukase Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Jun Kunisawa Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine Frontiers in Pharmacology alcaligenes lipid A adjuvant TI antigen haemophilus influenzae type B |
| 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 | alcaligenes lipid A adjuvant TI antigen haemophilus influenzae type B |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.763657/full |
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