# Alcaligenes lipid A as a sublingual adjuvant to augment protective immune responses in the respiratory and gastrointestinal tracts

## TL;DR

This study shows that Alcaligenes lipid A, when used as a sublingual adjuvant, boosts immune responses in the respiratory and gastrointestinal tracts, offering a promising approach for mucosal vaccination.

## Contribution

The study introduces sublingual administration of Alcaligenes-derived lipid A as a novel and effective adjuvant for mucosal vaccines.

## Key findings

- Sublingual immunization with Alcaligenes lipid A and OVA increased IgA in respiratory and gastrointestinal tracts.
- Lipid A elicited strong IgG responses and germinal center reactions without causing inflammation.
- Lipid A enhanced protection against cholera toxin and Streptococcus pneumoniae infections.

## Abstract

We previously identified Alcaligenes as symbiotic bacteria residing within Peyer’s patches and demonstrated that their primary components, lipopolysaccharides, and their active center, lipid A, are excellent adjuvants for mucosal vaccination. Here, we evaluated the effectiveness of Alcaligenes-derived lipid A as an adjuvant for sublingual immunization, a novel vaccination route. Mice sublingually immunized with Alcaligenes lipid A and ovalbumin (OVA) showed enhanced production of OVA-specific IgA in both the respiratory and gastrointestinal tracts. In addition, increased serum levels of OVA-specific and IgG antibodies were elicited through germinal center reactions in the draining lymph nodes without excessive inflammation at the administration sites. These results demonstrated superior efficacy not previously achieved through other routes of administration (e.g. intranasal, subcutaneous, intramuscular administration) or by existing adjuvants (e.g. CpG-ODN). In addition, sublingual immunization with cholera toxin B subunit (CTB) and lipid A led to an elevated CTB-specific IgG response in the systemic compartment and an elevated IgA response in the intestinal tract, effectively suppressing the diarrhea induced by oral challenge with cholera toxin. Furthermore, immunization with pneumococcal surface protein A (PspA) plus Alcaligenes lipid A elicited strong PspA-specific CD4+ T cell proliferation and Th17 responses, as well as IgA and IgG responses, in both the respiratory tract and the systemic compartment. These effects enhanced pneumococcal clearance in the lungs and subsequent protection against Streptococcus pneumoniae infection. Together, our findings suggest that Alcaligenes-derived lipid A is a potent sublingual vaccine adjuvant with potential efficacy against both respiratory and intestinal infectious diseases.

Sublingual lipid A is a potent mucosal adjuvant

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