Gold nanoparticles associated with ovalbumin as adjuvant in the indirect effects of oral tolerance improve ear wound healing in mice

Oral tolerance suppresses immune responses, such as antibody production, following immunization with an antigen and adjuvant in animals previously exposed to the protein orally. Parenteral administration of orally tolerated antigens with alum adjuvants induces systemic effects that inhibit immune responses to unrelated antigens and enhance wound healing in mouse skin. This study investigated whether subcutaneous (s.c.) administration of gold nanoparticles conjugated with ovalbumin (AuNPs@OVA) could serve as an effective adjuvant in oral tolerance and promote ear lesion repair in mice. Male Swiss mice received a 5-day oral OVA treatment, followed by s.c. injections of AuNPs@OVA at the tail base 7 days later, with a secondary injection administered 20 days after the initial dose. Lesions were created on one ear during the primary injection. Transmission electron microscopy (TEM) confirmed a spherical morphology of the AuNPs, with an average diameter of approximately 6.84 nm. The findings demonstrated that AuNPs@OVA injections enhanced IgG1, IgG2a, and total anti-OVA antibody levels in non-tolerant mice. Immunization also increased leukocyte levels at the injection site. In OVA-tolerant mice, AuNPs@OVA elevated the percentage of TBET-expressing cells in the caudal lymph nodes but not in the spleen. Histological analysis revealed improved ear tissue remodeling in OVA-tolerant mice treated with AuNPs@OVA compared to other groups. These results indicate that AuNPs@OVA injections not only leverage the indirect effects of oral tolerance but also outperform Al(OH)3 as an adjuvant in promoting ear wound healing.