Alteration of Biological Reaction in Aged Population Reduces Alpha-Toxin Vaccine Efficacy Against Staphylococcus Aureus Skin Infection 9098

Abstract Description Staphylococcus aureus (SA) is a leading cause of severe diseases that are difficult to treat, yet no successful vaccine has been investigated. The α-toxin (HLA), a key virulence factor, has been a primary vaccine target due to its immunogenicity and role in pathogenesis. However, HLA-based vaccines are primarily tested in young, healthy models, neglecting vulnerable populations like the elderly and other immunocompromised individuals. Our study reveals that both the active and passive HLA vaccines failed to protect against SA skin infections in aged mice models, which were linked to reduced pathogenesis of HLA due to reduced enzymatic activity of HLA receptor A Disintegrin and Metalloprotease 10 (ADAM10). Given the growing aged population, these findings highlight the limitations of current HLA-based vaccines for high-risk groups. Our study calls for vaccine strategies tailored to address population-specific immune differences, ensuring adequate protection for those most vulnerable to SA infections. Funding Sources R01AI144694, NIH R01 AI181321. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)