An epitope vaccine derived by analyzing clinical trial samples safeguards hosts with prior exposure to <i>S. aureus</i> against reinfection.

Abstract

Humans, as natural carriers of <i>Staphylococcus aureus</i> (SA), have developed nonprotective immune imprints that can be reactivated by SA antigen vaccination and that contribute to the failure of SA vaccine trials. To test whether an epitope-focused vaccine strategy can overcome this issue, we explored the protective epitope of the notable SA antigen MntC. A surface loop of MntC (Loop101) was found to be essential for SA to absorb manganese(II) ion and survive oxidative stress. Our Loop101-deficient versus -competent MntC-based differential screening identified a Loop101-specific human monoclonal antibody (Hm0686). Hm0686 blocked SA from absorbing manganese(II) ion and exhibited a strong opsonophagocytic activity, suggesting that Hm0686-targeted Loop101 may be a protective epitope. A Loop101 epitope vaccine but not the whole MntC antigen protected against SA infection in mice with prior exposure-induced nonprotective imprints. Thus, this effective protective epitope-based vaccine strategy may be explored to overcome nonprotective immune imprints in humans.