Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine

• Main Authors: Zilai Liu (Author), Koji Hosomi (Author), Atsushi Shimoyama (Author), Ken Yoshii (Author), Xiao Sun (Author), Huangwenxian Lan (Author), Yunru Wang (Author), Haruki Yamaura (Author), Davie Kenneth (Author), Azusa Saika (Author), Takahiro Nagatake (Author), Hiroshi Kiyono (Author), Koichi Fukase (Author), Jun Kunisawa (Author)
• Format: Book
• Published: Frontiers Media S.A., 2021-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1663-9812
10.3389/fphar.2021.763657