Efficacy of Active Immunization With Attenuated α-Hemolysin and Panton-Valentine Leukocidin in a Rabbit Model of Staphylococcus aureus Necrotizing Pneumonia

• Published in: The Journal of infectious diseases Vol. 221; no. 2; pp. 267 - 275
• Main 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
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 02.01.2020
• Subjects: Animals; Antibody response; Bacterial Toxins - administration & dosage; Bacterial Toxins - immunology; Disease Models, Animal; Drug resistance; Exotoxins - administration & dosage; Exotoxins - immunology; Hemolysin Proteins - administration & dosage; Hemolysin Proteins - immunology; Histocompatibility antigen HLA; Humans; Immunization; Lethality; Leukocidin; Leukocidins - administration & dosage; Leukocidins - immunology; Major and Brief Reports; Methicillin; Methicillin-Resistant Staphylococcus aureus; Pneumonia; Pneumonia, Necrotizing - immunology; Pneumonia, Necrotizing - prevention & control; Pneumonia, Staphylococcal - immunology; Pneumonia, Staphylococcal - prevention & control; Rabbits; Staphylococcus aureus; Staphylococcus infections; Toxoids; Vaccination; vaccine; antibodies; pneumonia; MRSA; α-toxin; PVL
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiz437

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.