{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T06:42:45Z","timestamp":1771742565166,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>We previously identified <jats:italic>Alcaligenes<\/jats:italic> spp. as a commensal bacterium that resides in lymphoid tissues, including Peyer\u2019s patches. We found that <jats:italic>Alcaligenes<\/jats:italic>-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 <jats:italic>Alcaligenes<\/jats:italic> lipid A as a safe synthetic vaccine adjuvant that induces Th17 polarization to enhance systemic IgG and respiratory IgA responses to T-cell\u2013dependent antigens (e.g., ovalbumin and pneumococcal surface protein A) without excessive inflammation. Here, we examined the adjuvant activity of <jats:italic>Alcaligenes<\/jats:italic> lipid A on a <jats:italic>Haemophilus<\/jats:italic> influenzae B conjugate vaccine that contains capsular polysaccharide polyribosyl ribitol phosphate (PRP), a T-cell\u2013independent antigen, conjugated with the T-cell\u2013dependent tetanus toxoid (TT) antigen (i.e., PRP-TT). When mice were subcutaneously immunized with PRP alone or mixed with TT, <jats:italic>Alcaligenes<\/jats:italic> 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\u2014deficient nude mice. Furthermore, TT-specific\u2014but not PRP-specific\u2014T-cell activation occurred in mice immunized with PRP-TT together with <jats:italic>Alcaligenes<\/jats:italic> lipid A. In addition, coculture with <jats:italic>Alcaligenes<\/jats:italic> lipid A promoted significant proliferation of and enhanced antibody production by B cells. Together, these findings suggest that <jats:italic>Alcaligenes<\/jats:italic> lipid A exerts an adjuvant activity on thymus-independent Hib polysaccharide antigen in the presence of a T-cell\u2013dependent conjugate carrier antigen.<\/jats:p>","DOI":"10.3389\/fphar.2021.763657","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T05:26:09Z","timestamp":1634880369000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine"],"prefix":"10.3389","volume":"12","author":[{"given":"Zilai","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Hosomi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Shimoyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Yoshii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huangwenxian","family":"Lan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunru","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruki","family":"Yamaura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davie","family":"Kenneth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azusa","family":"Saika","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Nagatake","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Kiyono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Fukase","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Kunisawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S57","DOI":"10.1093\/infdis\/136.supplement.s57","article-title":"Antibody of Polyribophate of Haemophilus Influenzae Type B in Infants and Children: Effect of Immunization with Polyribophosphate","volume":"136","author":"Anderson","year":"1977","journal-title":"J. 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