Identifying protective antigens of Staphylococcus aureus, a pathogen that suppresses host immune responses.

Staphylococcus aureus infections result in abscesses as well as septicemia. Even with therapy, abscesses can persist or even reoccur, as staphylococcal infections fail to induce protective immune responses. Here, we show that prior infection with certain attenuated strains may elicit protective immunity. A closer examination reveals that protection correlates with antibody responses elicited on exposure to particular attenuated variants. Linear regression analysis was used to compare reduction in staphylococcal disease and antibody responses to infection with wild-type and attenuated variants. This analysis identified protective antigens that, when tested as vaccines in mice, elicited disease protection. Protection afforded by attenuated strains correlates in part with the ability of Staphylococcus aureus to modulate B cell responses via protein A (spa encoded). We designate this approach "genetic vaccinology," since it exploits genetic variants to draw a correlation between disease protection and humoral immune responses for the deduction of vaccine antigens. Genetic vaccinology is particularly useful for microbes that do not elicit natural protective immunity during infection.