# Dual-Function Adjuvant Cyclosporin A: Enhancing RSV-Specific Humoral Immunity via Treg-Driven B-Cell Activation

## TL;DR

This study shows that Cyclosporin A, usually an immunosuppressant, can boost RSV-specific antibodies in mice by activating regulatory T cells that help B cells.

## Contribution

CsA is repurposed as a dual-function adjuvant that enhances RSV immunity via Treg-driven B-cell activation.

## Key findings

- Co-administration of CsA with RSV G protein boosts RSV-specific IgG and neutralizing antibodies.
- CsA-induced Tregs express CD40L and IL-10, promoting B-cell activation and plasma cell differentiation.
- Treg depletion or IL-10/CD40L neutralization abrogates antibody production, confirming their critical role.

## Abstract

Background: Respiratory syncytial virus (RSV) remains a leading cause of respiratory illness globally, with limited vaccine options, particularly for infants and high-risk populations. This study investigates Cyclosporin A (CsA), traditionally an immunosuppressant, as a novel adjuvant to enhance RSV-specific immunity. Methods: BALB/c mice were subcutaneously immunized with RSV G protein co-administered with varying Cyclosporin A doses, challenged intranasally with RSV, and analyzed for RSV-specific humoral immunity and mechanistic Treg-dependent B-cell responses. Results: We demonstrate that co-administration of CsA with the RSV G protein (G+CsA) dose-dependently boosts RSV-specific IgG and neutralizing antibodies, with selective augmentation of IgG1 and IgG2 subclasses. Mechanistically, G+CsA induces regulatory T cells (Tregs) expressing CD40L and IL-10, which directly promote B-cell activation, proliferation, and plasma cell differentiation. Depletion of Tregs or neutralization of IL-10/CD40L abrogated antibody production, confirming these pathways as critical mediators. Notably, G+CsA-induced Tregs adopt a helper phenotype distinct from conventional Tregs, balancing immune enhancement and homeostasis. Conclusions: CsA demonstrates dual adjuvant properties by enhancing RSV-specific neutralizing IgG titers through Treg-driven B-cell activation, offering a potential strategy to optimize vaccine-induced humoral immunity.