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Our previous study demonstrated that lipopolysaccharide (LPS) from Peyer\u2019s patch resident Alcaligenes stimulated dendritic cells to promote the production of mucosal immunity-enhancing cytokines (e.g., IL-6 and BAFF), thus enhancing antigen-specific immune responses (including IgA production and Th17 responses) without excessive inflammation. Here, we chemically synthesized Alcaligenes lipid A, the biologically active part of LPS, and examined its efficacy as a nasal vaccine adjuvant for the induction of protectively immunity against Streptococcus pneumoniae infection. Mice were nasally immunized with pneumococcal surface protein A (PspA) as a vaccine antigen for S. pneumoniae, together with Alcaligenes lipid A. Alcaligenes lipid A supported the generation of high levels of PspA-specific IgA and IgG responses through the augmentation of germinal center formation in the nasopharynx-associated lymphoid tissue and cervical lymph nodes (CLNs). Moreover, Alcaligenes lipid A promoted PspA-specific CD4+ Th17 responses in the CLNs and spleen. Furthermore, neutrophils were recruited to infection sites upon nasal infection and synchronized with the antigen-specific T and B cell responses, resulting in the protection against S. pneumoniae infection. Taken together, Alcaligenes lipid A could be applied to the prospective adjuvant to enhance nasal vaccine efficacy by means of augmenting both the innate and acquired arms of mucosal immunity against respiratory bacterial infection.<\/jats:p>","DOI":"10.3390\/microorganisms8081102","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T10:14:06Z","timestamp":1595499246000},"page":"1102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Chemically Synthesized Alcaligenes Lipid A Shows a Potent and Safe Nasal Vaccine Adjuvant Activity for the Induction of Streptococcus pneumoniae-Specific IgA and Th17 Mediated Protective Immunity"],"prefix":"10.3390","volume":"8","author":[{"given":"Ken","family":"Yoshii","sequence":"first","affiliation":[{"name":"Laboratory 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"},{"name":"Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Hosomi","sequence":"additional","affiliation":[{"name":"Laboratory 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1910-0450","authenticated-orcid":false,"given":"Atsushi","family":"Shimoyama","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Graduate School of Science, Osaka University, Osaka 560-0043, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunru","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory 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"},{"name":"Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Yamaura","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Graduate School of Science, Osaka University, Osaka 560-0043, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Nagatake","sequence":"additional","affiliation":[{"name":"Laboratory 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Laboratory 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangwenxian","family":"Lan","sequence":"additional","affiliation":[{"name":"Laboratory 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"},{"name":"Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kiyono","sequence":"additional","affiliation":[{"name":"International Research and Development Center for Mucosal Vaccines, the Institute of Medical Science, the University of Tokyo (IMSUT), Tokyo 108-8639, Japan"},{"name":"IMSUT Distinguished Professor Unit, the Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan"},{"name":"Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"},{"name":"Department of Medicine, School of Medicine and Chiba University-University of California San Diego (CU-UCSD) Center for Mucosal Immunology, Allergy and Vaccine, University of California, Oakland, CA 92093-0063, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8844-0710","authenticated-orcid":false,"given":"Koichi","family":"Fukase","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Graduate School of Science, Osaka University, Osaka 560-0043, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Kunisawa","sequence":"additional","affiliation":[{"name":"Laboratory 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"},{"name":"Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan"},{"name":"Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan"},{"name":"International Research and Development Center for Mucosal Vaccines, the Institute of Medical Science, the University of Tokyo (IMSUT), Tokyo 108-8639, Japan"},{"name":"Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan"},{"name":"Department of Microbiology and Immunology, Graduate School of Medicine, Kobe University, Hyogo 650-0017, Japan"},{"name":"Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 739-0046, Japan"},{"name":"Research Organization for Nano &amp; Life Innovation, Waseda University, Tokyo 162-0041, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.it.2008.07.008","article-title":"Immunological commonalities and distinctions between airway and digestive immunity","volume":"29","author":"Kunisawa","year":"2008","journal-title":"Trends Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1248\/yakushi.14-00006-3","article-title":"The development of mucosal vaccine using bacterial function for targeting mucosal tissues","volume":"134","author":"Suzuki","year":"2014","journal-title":"Yakugaku Zasshi."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nri1439","article-title":"NALT- versus Peyer\u2019s-patch-mediated mucosal 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