Details

Autor(en) / Beteiligte

• Han, Xiaobing
• Ortines, Roger
• Mukherjee, Ipsita
• Kanipakala, Tulasikumari
• Kort, Thomas
• Sherchand, Shardulendra P
• Liao, Grant
• Mednikov, Mark
• Chenine, Agnes L
• Aman, M Javad
• Nykiforuk, Cory L
• Adhikari, Rajan P

Titel

Hyperimmune Targeting Staphylococcal Toxins Effectively Protect Against USA 300 MRSA Infection in Mouse Bacteremia and Pneumonia Models

Ist Teil von

• Frontiers in immunology, 2022-05, Vol.13, p.893921-893921

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2022

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• has been acquiring multiple drug resistance and has evolved into superbugs such as Methicillin/Vancomycin-resistant (MRSA/VRSA) and, consequently, is a major cause of nosocomial and community infections associated with high morbidity and mortality for which no FDA-approved vaccines or biotherapeutics are available. Previous efforts targeting the surface-associated antigens have failed in clinical testing. Here, we generated hyperimmune products from sera in rabbits against six major toxins targeted by an experimental vaccine (IBT-V02) and demonstrated significant efficacy for an anti-virulence passive immunization strategy. Extensive binding and neutralizing titers were analyzed against six extracellular toxins from individual animal sera. All IBT-V02 immunized animals elicited the maximum immune response upon the first boost dose against all pore-forming vaccine components, while for superantigen (SAgs) components of the vaccine, second and third doses of a boost were needed to reach a plateau in binding and toxin neutralizing titers. Importantly, both anti-staphylococcus hyperimmune products consisting of full-length IgG (IBT-V02-IgG) purified from the pooled sera and de-speciated F(ab') (IBT-V02-F(ab')2) retained the binding and neutralizing titers against IBT-V02 target toxins. F(ab') also exhibited cross-neutralization titers against three leukotoxins (HlgAB, HlgCB, and LukED) and four SAgs (SEC1, SED, SEK, and SEQ) which were not part of IBT-V02. F(ab') also neutralized toxins in bacterial culture supernatant from major clinical strains of . efficacy data generated in bacteremia and pneumonia models using USA300 strain demonstrated dose-dependent protection by F(ab') . These efficacy data confirmed the staphylococcal toxins as viable targets and support the further development effort of hyperimmune products as a potential adjunctive therapy for emergency uses against life-threatening infections.