Efficacy Of Active Immunization With Attenuated Alpha-Hemolysin And Panton-Valentine Leukocidin In A Rabbit Model Of Staphylococcus Aureus Necrotizing Pneumonia

Staphylococcus aureus is a common pathogen causing infections in humans with various degrees of severity, with pneumonia being one of the most severe infections. In as much as staphylococcal pneumonia is a disease driven in large part by alpha-hemolysin (Hla) and Panton-Valentine leukocidin (PVI,), we evaluated whether active immunization with attenuated forms of Hla (Hla (H35L/H48L)) alone, PVL components (LukS-PVT28F/K97 A/S209 A and LukF-PVK102 A) alone, or combination of all 3 toxoids could prevent lethal challenge in a rabbit model of necrotizing pneumonia caused by the USA300 community-associated methicillin-resistant S. aureus (MRSA). Rabbits vaccinated with Hla toxoid alone or PV1, components alone were only partially protected against lethal pneumonia, whereas those vaccinated with all 3 toxoids had 100% protection against lethality. Vaccine-mediated protection correlated with induction of polyclonal antibody response that neutralized not only alpha-hemolysin and PVL, but also other related toxins, produced by USA300 and other epidemic MRSA clones.