Lipopolysaccharide Derived From the Lymphoid-Resident Commensal Bacteria Alcaligenes faecalis Functions as an Effective Nasal Adjuvant to Augment IgA Antibody and Th17 Cell Responses

Abstract

Alcaligenes spp., including A. faecalis, is a gram-negative facultative bacterium uniquely residing inside the Peyer’s patches. We previously showed that A. faecalis-derived lipopolysaccharides (Alcaligenes LPS) acts as a weak agonist of toll-like receptor 4 to activate dendritic cells and shows adjuvant activity by enhancing IgG and Th17 responses to systemic vaccination. Here, we examined the efficacy of Alcaligenes LPS as a nasal vaccine adjuvant. Nasal immunization with ovalbumin (OVA) plus Alcaligenes LPS induced follicular T helper cells and germinal center formation in the nasopharynx-associated lymphoid tissue (NALT) and cervical lymph nodes (CLNs), and consequently enhanced OVA-specific IgA and IgG responses in the respiratory tract and serum. In addition, nasal immunization with OVA plus Alcaligenes LPS induced OVA-specific T cells producing IL-17 and/or IL-10, whereas nasal immunization with OVA plus cholera toxin (CT) induced OVA-specific T cells producing IFN-γ and IL-17, which are recognized as pathogenic type of Th17 cells. In addition, CT, but not Alcaligenes LPS, promoted the production of TNF-α and IL-5 by T cells. Nasal immunization with OVA plus CT, but not Alcaligenes LPS, led to increased numbers of neutrophils and eosinophils in the nasal cavity. Together, these findings indicate that the benign nature of Alcaligenes LPS is an effective nasal vaccine adjuvant that induces antigen-specific mucosal and systemic immune responses without activation of inflammatory cascade after nasal administration.

ADP-ribosylating adjuvant reveals plasticity in cDC1 cells that drive mucosal Th17 cell development and protection against influenza virus infection

“…5b and Supplementary Fig. 4a ) 47 . Moreover, both CTA1-adjuvants effectively primed OT II CD4 T cells in the absence of cDC2DP cells in the huCD207/DTA mice (Fig.…”

“…Thus, the target population was restricted to cDC1 and did not depend on cDC2DP cells, despite that the latter carry CD103. In fact, huCD207DTU mice that were deficient in cCD2DP cells in mLN demonstrated full adjuvant and antigenic properties in response to the fusion protein, while Batf3−/−mice, lacking cDC1 cells, did not respond to CD103- or DD-targeting, but reacted to other adjuvants given intranasally 45 – 47 .…”

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

“…We previously reported that Alcaligenes LPS acts as an TLR4 agonist, thereby enhancing antigen-specific immune responses without excessive inflammation and leading to the possibility of its use as a safe adjuvant (Shibata et al, 2018;Wang et al, 2021). LPS is mainly composed of lipid A, core oligosaccharide, and O antigen among which lipid A is considered to be the active site of LPS and major determinant of LPS activity.…”

“…These characteristics prompted us to evaluate Alcaligenes-derived LPS and lipid A as a new and safe adjuvant candidate. Indeed, we found that both purified Alcaligenes LPS and chemically synthesized lipid A enhanced antibody production and Th17 responses to systemically or nasally immunized antigens (i.e., ovalbumin and pneumococcal surface protein A [PspA], a surface virulence factor of Streptococcus pneumoniae) (Wang et al, 2020;Yoshii et al, 2020;Wang et al, 2021).…”

“…Although our previous studies (Wang et al, 2020;Yoshii et al, 2020;Wang et al, 2021) demonstrated that Alcaligenes lipid A is an effective adjuvant for TD antigens such as ovalbumin and PspA, whether it also efficiently boosts the antigenicity of TI antigens remained unclear. Here we aimed to extend the application of Alcaligenes lipid A by determining its adjuvanticity on a Haemophilus B conjugate vaccine as an example TI antigen-based conjugate vaccine.…”