Efficacy of Active Immunization With Attenuated α-Hemolysin and Panton-Valentine Leukocidin in a Rabbit Model of Staphylococcus aureus Necrotizing Pneumonia. (26th August 2019)

• Record Type: Journal Article
• Authors: Tran, Vuvi G; Venkatasubramaniam, Arundhathi; Adhikari, Rajan P; Krishnan, Subramaniam; Wang, Xing; Le, Vien T M; Le, Hoan N; Vu, Trang T T; Schneider-Smith, Erika; Aman, M Javad; Diep, Binh An
• Is Part Of: Journal of infectious diseases. Volume 221:Number 2(2020)
• Page Start: 267
• Page End: 275
• Publication Date: 2019-08-26
• Subjects: MRSA -- pneumonia -- α-toxin -- PVL -- antibodies -- vaccine; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiz437
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: 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 α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL), we evaluated whether active immunization with attenuated forms of Hla (HlaH35L/H48L ) alone, PVL components (LukS-PVT28F/K97A/S209A and LukF-PVK102A ) 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 PVL 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 α-hemolysin and PVL, but also other related toxins, produced by USA300 and other epidemic MRSA clones.