Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine
Year: 2021
Type: article
Abstract: 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.
Source: Frontiers in Pharmacology
Institutions: National Institute of Biomedical Innovation, Health and Nutrition, National Institute of Biomedical Innovation, The University of Osaka, Chiba University, University of California San Diego, Future Medicine Education and Research Organization at Chiba University, Institute of Medical Science, The University of Tokyo, The University of Tokyo, Waseda University, Kobe University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: Canon Foundation in Europe, Japan Agency for Medical Research and Development, Ministry of Education, Culture, Sports, Science and Technology, Ministry of Health, Labour and Welfare, University of Tokyo, Ono Medical Research Foundation, National Institutes of Biomedical Innovation, Health and Nutrition, Japan Society for the Promotion of Science, Institute of Medical Science, University of Tokyo
Awards: G1264619005, G1278042198, G1305213375, G1323010525, G132339150, Research for constituents of microbiome in twins, G1483461569, G1647381326, G1682803251, G1872578030, Functional analysis of glycans and immunoregulation by using synthetic glycans and glycan remodeling, Mechanism of adaptation to a low-protein diet observed among the indigenous population of New Guinea Island, whose primary sustenance revolves around sago starch., Elucidation of glycan function by synthetic glycans and glycan remodeling systems and their application to new immunotherapies, G2320037144, G2363237036, G239211905, G2419081138, G265389467, G2716568321, G2827252697, G3184950637, G3345551801, G348620180, Immune modulation by a symbiotic bacterium Alcaligenes in gut associated lymphoid tissues, Assessement of relationship between gut dysbyosis and pathogenesis of pulmonary hypertension, G4012452508, G4087806862, G4105453854, G4531321360, 糖尿病個別化予防を加速するマイクロバイオーム解析AIの開発, G4643215137, G5005590050, G5172788151, G5296029281, G5302586464, G5770918211, G5771238525, G5916716846, G5986500842, Synthesis of lipooligosaccharides partial structures including 2,3-diaminoglucose disaccharide skeleton for the elucidation of autoimmune disease onset mechanism, G6164904077, G6176851202, G6276915214, G6285829330, G6599669833, G6637831528, G6835991875, G7201795159, G7311990908, Regulation of immunometabolism in the dendritic cells by intratissue commensal bacteria, G7427590184, G7467865565, Study of the mechanism of functional food ingredients through the control of intestinal signals, G7763165865, G7891218493, G7933571598, Understanding the mechanism of the cutaneous immune-diversity and its relationship with other organs, G8080270101, G8120304202, G83060929, Development of Highly Functionalized Lipid A and its Application to Innate and Acquired Immune Regulatory Molecules, G864087039, G8734479758, G884255588, G8964687884, G949121936
OpenAlex ID: W3209918014