# Augmenting Subunit-Vaccine-Induced Immunity through a Dual Strategy of Gold Nanoparticle Conjugation and Chitosan Microneedle-Mediated Sustained Delivery

## TL;DR

This study combines gold nanoparticles and chitosan microneedles to improve subunit vaccine effectiveness by boosting immune responses and prolonging antigen exposure.

## Contribution

A novel dual strategy using gold nanoparticle conjugation and chitosan microneedles to enhance subunit vaccine immunogenicity and durability.

## Key findings

- GNP–OVA conjugates enhanced dendritic cell maturation and antigen presentation.
- GNP–OVA MNs induced stronger and longer-lasting immune responses compared to traditional subcutaneous vaccination.
- The platform reduced reliance on external adjuvants and showed potential for next-generation vaccines.

## Abstract

Subunit vaccines offer high safety but often exhibit
low immunogenicity
and rapid clearance and require adjuvants. In this study, we developed
a dual strategy for augmenting subunit-vaccine-induced immune responses
by integrating self-adjuvanting gold nanoparticle (GNP)-antigen conjugates
with implantable chitosan (CS) microneedles (MNs) to achieve sustained
intradermal antigen exposure. Conjugation of a model antigen, namely,
ovalbumin (OVA), onto the GNP surface (GNP–OVA) resulted in
virus-mimicking multivalent antigen display, which substantially enhanced
dendritic cell maturation, as evidenced by the upregulation of CD86
and major histocompatibility complex class II. This conjugation strategy
also enabled the efficient codelivery of the antigen and carrier into
the same antigen-presenting cells, thereby facilitating improved antigen
presentation. Furthermore, compared with free OVA and a physical GNP/OVA
mixture, conjugated GNP–OVA exhibited considerably longer lymph
node retention, primarily because of its nanovaccine properties, which
facilitate its preferential trafficking into lymphatic vessels and
its subsequent accumulation in lymph nodes. Encapsulation of GNP–OVA
into CS MNs (i.e., GNP–OVA MNs) resulted in reliable skin implantation,
sustained intradermal antigen exposure, and local immune cell recruitment.
Rat immunization studies revealed that GNP–OVA MNs induced
balanced T helper 1 and T helper 2 responses and elicited considerably
higher and more durable OVA-specific immunoglobulin G levels than
did subcutaneous vaccination with GNP–OVA or OVA alone. These
responses persisted for at least 16 weeks, highlighting the potential
of the developed platform for prolonged subunit vaccine immunization.
This dual-strategy platform, combining virus-mimicking GNP-based nanovaccines
with immunostimulatory CS MNs, reduces reliance on external adjuvants
and enhances the potency and durability of subunit vaccines. Its modular
and patient-friendly design underscores its high potential for advancing
the development of next-generation vaccines against emerging infectious
diseases.