Alcaligenes lipid A functions as a superior mucosal adjuvant to monophosphoryl lipid A via the recruitment and activation of CD11b+ dendritic cells in nasal tissue

Xiao Sun; Koji Hosomi; Atsushi Shimoyama; Ken Yoshii; Azusa Saika; Haruki Yamaura; Takahiro Nagatake; Hiroshi Kiyono; Koichi Fukase; Jun Kunisawa

doi:10.1093/intimm/dxad045

Alcaligenes lipid A functions as a superior mucosal adjuvant to monophosphoryl lipid A via the recruitment and activation of CD11b+ dendritic cells in nasal tissue

Int Immunol. 2024 Jan 29;36(1):33-43. doi: 10.1093/intimm/dxad045.

Authors

Xiao Sun^{1

2}, Koji Hosomi¹, Atsushi Shimoyama^{3

4}, Ken Yoshii^{1

5}, Azusa Saika¹, Haruki Yamaura³, Takahiro Nagatake^{1

6}, Hiroshi Kiyono^{7

8

9

10}, Koichi Fukase^{3

4}, Jun Kunisawa^{1

2

3

4

5

11

12

13

14}

Affiliations

¹ Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan.
² Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
³ Department of Chemistry, Graduate School of Science, Osaka University, Osaka 560-0043, Japan.
⁴ Collaborative Research Between NIBIOHN and Graduate School of Science, Forefront Research Center, Osaka University, Osaka 560-0043, Japan.
⁵ Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
⁶ Department of Life Sciences, Laboratory of Functional Anatomy, School of Agriculture, Meiji University, Kanagawa 214-8571, Japan.
⁷ Division of Gastroenterology, Department of Medicine, University of California San Diego (UCSD), San Diego, CA 92093, USA.
⁸ Chiba University (CU)-UCSD Center for Mucosal Immunology, Allergy and Vaccines (cMAV), UCSD, San Diego, CA 92093-0063, USA.
⁹ Future Medicine Education and Research Organization, Chiba University, Chiba 260-8670, Japan.
¹⁰ Department of Human Mucosal Vaccinology, Chiba University Hospital, Chiba 260-8677, Japan.
¹¹ International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
¹² Department of Microbiology and Immunology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
¹³ Research Organization for Nano and Life Innovation, Waseda University, Tokyo 162-0041, Japan.
¹⁴ Graduate School of Dentistry, Osaka University, Suita 565-0871, Japan.

Abstract

We previously demonstrated that Alcaligenes-derived lipid A (ALA), which is produced from an intestinal lymphoid tissue-resident commensal bacterium, is an effective adjuvant for inducing antigen-specific immune responses. To understand the immunologic characteristics of ALA as a vaccine adjuvant, we here compared the adjuvant activity of ALA with that of a licensed adjuvant (monophosphoryl lipid A, MPLA) in mice. Although the adjuvant activity of ALA was only slightly greater than that of MPLA for subcutaneous immunization, ALA induced significantly greater IgA antibody production than did MPLA during nasal immunization. Regarding the underlying mechanism, ALA increased and activated CD11b+ CD103- CD11c+ dendritic cells in the nasal tissue by stimulating chemokine responses. These findings revealed the superiority of ALA as a mucosal adjuvant due to the unique immunologic functions of ALA in nasal tissue.

Keywords: Alcaligenes; MPLA; chemokines; lipid A; nasal vaccine; stromal cells.

MeSH terms

Adjuvants, Immunologic / pharmacology
Alcaligenes*
Animals
Dendritic Cells
Lipid A* / pharmacology
Mice

Substances

monophosphoryl lipid A
Lipid A
Adjuvants, Immunologic

Abstract

MeSH terms

Substances

Grants and funding