Adjuvant Activity of Synthetic Lipid A of <i>Alcaligenes</i>, a Gut-Associated Lymphoid Tissue-Resident Commensal Bacterium, to Augment Antigen-Specific IgG and Th17 Responses in Systemic Vaccine
<i>Alcaligenes</i> spp. are identified as commensal bacteria and have been found to inhabit Peyer’s patches in the gut. We previously reported that <i>Alcaligenes</i>-derived lipopolysaccharides (LPS) exerted adjuvant activity in systemic vaccination, without excessive inflam...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/3/395 |
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| author | Yunru Wang Koji Hosomi Atsushi Shimoyama Ken Yoshii Haruki Yamaura Takahiro Nagatake Tomomi Nishino Hiroshi Kiyono Koichi Fukase Jun Kunisawa |
| author_facet | Yunru Wang Koji Hosomi Atsushi Shimoyama Ken Yoshii Haruki Yamaura Takahiro Nagatake Tomomi Nishino Hiroshi Kiyono Koichi Fukase Jun Kunisawa |
| author_sort | Yunru Wang |
| collection | DOAJ |
| description | <i>Alcaligenes</i> spp. are identified as commensal bacteria and have been found to inhabit Peyer’s patches in the gut. We previously reported that <i>Alcaligenes</i>-derived lipopolysaccharides (LPS) exerted adjuvant activity in systemic vaccination, without excessive inflammation. Lipid A is one of the components responsible for the biological effect of LPS and has previously been applied as an adjuvant. Here, we examined the adjuvant activity and safety of chemically synthesized <i>Alcaligenes</i> lipid A. We found that levels of OVA-specific serum IgG antibodies increased in mice that were subcutaneously immunized with ovalbumin (OVA) plus <i>Alcaligenes</i> lipid A relative to those that were immunized with OVA alone. In addition, <i>Alcaligenes</i> lipid A promoted antigen-specific T helper 17 (Th17) responses in the spleen; upregulated the expression of MHC class II, CD40, CD80, and CD86 on bone marrow-derived dendritic cells (BMDCs); enhanced the production of Th17-inducing cytokines IL-6 and IL-23 from BMDCs. Stimulation with <i>Alcaligenes</i> lipid A also induced the production of IL-6 and IL-1β in human peripheral blood mononuclear cells. Moreover, <i>Alcaligenes</i> lipid A caused minor side effects, such as lymphopenia and thrombocytopenia. These findings suggest that <i>Alcaligenes</i> lipid A is a safe and effective Th17-type adjuvant by directly stimulating dendritic cells in systemic vaccination. |
| first_indexed | 2024-03-10T18:21:15Z |
| format | Article |
| id | doaj.art-df95d71e756c40f49b91c47ab1937da4 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T18:21:15Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-df95d71e756c40f49b91c47ab1937da42023-11-20T07:19:27ZengMDPI AGVaccines2076-393X2020-07-018339510.3390/vaccines8030395Adjuvant Activity of Synthetic Lipid A of <i>Alcaligenes</i>, a Gut-Associated Lymphoid Tissue-Resident Commensal Bacterium, to Augment Antigen-Specific IgG and Th17 Responses in Systemic VaccineYunru Wang0Koji Hosomi1Atsushi Shimoyama2Ken Yoshii3Haruki Yamaura4Takahiro Nagatake5Tomomi Nishino6Hiroshi Kiyono7Koichi Fukase8Jun Kunisawa9Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, 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), Osaka 567-0085, JapanDepartment of Chemistry, Graduate School of Science, Osaka University, Osaka 560-0043, 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), Osaka 567-0085, JapanDepartment of Chemistry, Graduate School of Science, Osaka University, Osaka 560-0043, 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), Osaka 567-0085, 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), Osaka 567-0085, JapanInternational Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, JapanDepartment of Chemistry, Graduate School of Science, Osaka University, Osaka 560-0043, 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), Osaka 567-0085, Japan<i>Alcaligenes</i> spp. are identified as commensal bacteria and have been found to inhabit Peyer’s patches in the gut. We previously reported that <i>Alcaligenes</i>-derived lipopolysaccharides (LPS) exerted adjuvant activity in systemic vaccination, without excessive inflammation. Lipid A is one of the components responsible for the biological effect of LPS and has previously been applied as an adjuvant. Here, we examined the adjuvant activity and safety of chemically synthesized <i>Alcaligenes</i> lipid A. We found that levels of OVA-specific serum IgG antibodies increased in mice that were subcutaneously immunized with ovalbumin (OVA) plus <i>Alcaligenes</i> lipid A relative to those that were immunized with OVA alone. In addition, <i>Alcaligenes</i> lipid A promoted antigen-specific T helper 17 (Th17) responses in the spleen; upregulated the expression of MHC class II, CD40, CD80, and CD86 on bone marrow-derived dendritic cells (BMDCs); enhanced the production of Th17-inducing cytokines IL-6 and IL-23 from BMDCs. Stimulation with <i>Alcaligenes</i> lipid A also induced the production of IL-6 and IL-1β in human peripheral blood mononuclear cells. Moreover, <i>Alcaligenes</i> lipid A caused minor side effects, such as lymphopenia and thrombocytopenia. These findings suggest that <i>Alcaligenes</i> lipid A is a safe and effective Th17-type adjuvant by directly stimulating dendritic cells in systemic vaccination.https://www.mdpi.com/2076-393X/8/3/395<i>Alcaligenes faecalis</i>Th17lipid A |
| spellingShingle | Yunru Wang Koji Hosomi Atsushi Shimoyama Ken Yoshii Haruki Yamaura Takahiro Nagatake Tomomi Nishino Hiroshi Kiyono Koichi Fukase Jun Kunisawa Adjuvant Activity of Synthetic Lipid A of <i>Alcaligenes</i>, a Gut-Associated Lymphoid Tissue-Resident Commensal Bacterium, to Augment Antigen-Specific IgG and Th17 Responses in Systemic Vaccine Vaccines <i>Alcaligenes faecalis</i> Th17 lipid A |
| title | Adjuvant Activity of Synthetic Lipid A of <i>Alcaligenes</i>, a Gut-Associated Lymphoid Tissue-Resident Commensal Bacterium, to Augment Antigen-Specific IgG and Th17 Responses in Systemic Vaccine |
| title_full | Adjuvant Activity of Synthetic Lipid A of <i>Alcaligenes</i>, a Gut-Associated Lymphoid Tissue-Resident Commensal Bacterium, to Augment Antigen-Specific IgG and Th17 Responses in Systemic Vaccine |
| title_fullStr | Adjuvant Activity of Synthetic Lipid A of <i>Alcaligenes</i>, a Gut-Associated Lymphoid Tissue-Resident Commensal Bacterium, to Augment Antigen-Specific IgG and Th17 Responses in Systemic Vaccine |
| title_full_unstemmed | Adjuvant Activity of Synthetic Lipid A of <i>Alcaligenes</i>, a Gut-Associated Lymphoid Tissue-Resident Commensal Bacterium, to Augment Antigen-Specific IgG and Th17 Responses in Systemic Vaccine |
| title_short | Adjuvant Activity of Synthetic Lipid A of <i>Alcaligenes</i>, a Gut-Associated Lymphoid Tissue-Resident Commensal Bacterium, to Augment Antigen-Specific IgG and Th17 Responses in Systemic Vaccine |
| title_sort | adjuvant activity of synthetic lipid a of i alcaligenes i a gut associated lymphoid tissue resident commensal bacterium to augment antigen specific igg and th17 responses in systemic vaccine |
| topic | <i>Alcaligenes faecalis</i> Th17 lipid A |
| url | https://www.mdpi.com/2076-393X/8/3/395 |
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