# Differential Immune Response Patterns Induced by Anionic and Cationic Lipid Adjuvants in Intranasal Anti-Influenza Immunization

## TL;DR

This study compares how anionic and cationic lipid adjuvants affect immune responses in mice vaccinated against influenza, showing distinct immune patterns.

## Contribution

The study reveals how adjuvant charge influences specific immune cell populations and responses in intranasal influenza vaccination.

## Key findings

- Cationic adjuvant N3 enhances cDC1, MHCI, CD8T, and Th17 responses with higher IFNγ expression.
- Anionic adjuvant L3 increases cDC2, MHCII, and humoral responses with higher IgG/IgA and virus neutralization.
- Cationic adjuvants favor Th1/Th17 responses, while anionic adjuvants favor CD4T and regulatory T cells.

## Abstract

Currently, vaccine development against different respiratory diseases is at its peak. It is of utmost importance to find suitajble adjuvants that can increase the potency of the vaccine candidates. This study aimed to determine the systemic and splenic immune mechanisms in mice models induced by anionic and cationic lipid adjuvants in the presence of the vaccine-candidate influenza antigen hemagglutinin (HA). In the presence of the HA antigen, the cationic adjuvant (N3) increased conventional dendritic cell 1 (cDC1) abundance with enhanced MHCI and CD80-CD86 costimulatory marker expression, and significantly higher CD8T and Th17 populations with enhanced interferon-gamma (IFNγ) expression in CD8T and CD4T populations. Conversely, the anionic adjuvant (L3) increased the cDC2 population percentage with significantly higher MHCII and DEC205 expression, along with an increase in the CD4T and regulatory T cell populations. The L3-treated group also exhibited higher percentages of activated B and plasma cell populations with significantly higher antigen-specific IgG and IgA titer and virus neutralization potential. While the anionic adjuvant induced significantly higher humoral responses than the cationic adjuvant, the latter influenced a significantly higher Th1/Th17 response. For customized vaccine development, it is beneficial to have alternative adjuvants that can generate differential immune responses with the same vaccine candidate antigen. This study will aid the selection of adjuvants based on their charges to improve specific immune response arms in the future development of vaccine formulation.