Frontiers in Pharmacology (Oct 2021)

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

  • Zilai Liu,
  • Zilai Liu,
  • Koji Hosomi,
  • Atsushi Shimoyama,
  • Ken Yoshii,
  • Ken Yoshii,
  • Xiao Sun,
  • Xiao Sun,
  • Huangwenxian Lan,
  • Huangwenxian Lan,
  • Yunru Wang,
  • Yunru Wang,
  • Haruki Yamaura,
  • Davie Kenneth,
  • Azusa Saika,
  • Azusa Saika,
  • Takahiro Nagatake,
  • Hiroshi Kiyono,
  • Hiroshi Kiyono,
  • Hiroshi Kiyono,
  • Hiroshi Kiyono,
  • Hiroshi Kiyono,
  • Koichi Fukase,
  • Jun Kunisawa,
  • Jun Kunisawa,
  • Jun Kunisawa,
  • Jun Kunisawa,
  • Jun Kunisawa,
  • Jun Kunisawa,
  • Jun Kunisawa,
  • Jun Kunisawa

DOI
https://doi.org/10.3389/fphar.2021.763657
Journal volume & issue
Vol. 12

Abstract

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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.

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