Monoclonal antibodies against lipopolysaccharide protect against Pseudomonas aeruginosa challenge in mice

• Published in: Frontiers in cellular and infection microbiology 2023-06, Vol.13, p.1191806-1191806
• Main Authors: Kang, Jason, Mateu-Borrás, Margalida, Monroe, Hunter L, Sen-Kilic, Emel, Miller, Sarah Jo, Dublin, Spencer R, Huckaby, Annalisa B, Yang, Evita, Pyles, Gage M, Nunley, Mason A, Chapman, Josh A, Amin, Md Shahrier, Damron, F Heath, Barbier, Mariette
• Format: Article
• Language: English
• Subjects: ammonium metavanadate; Animals; anti-lipopolysaccharide antibody; Antibodies, Bacterial; Antibodies, Monoclonal; Cellular and Infection Microbiology; Lipopolysaccharides; Mice; monoclonal antibody (mAb); Pseudomonas aeruginosa; Pseudomonas Infections - microbiology; sepsis; Sepsis - drug therapy
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2023.1191806

is a common cause of hospital-acquired infections, including central line-associated bloodstream infections and ventilator-associated pneumonia. Unfortunately, effective control of these infections can be difficult, in part due to the prevalence of multi-drug resistant strains of . There remains a need for novel therapeutic interventions against , and the use of monoclonal antibodies (mAb) is a promising alternative strategy to current standard of care treatments such as antibiotics. To develop mAbs against , we utilized ammonium metavanadate, which induces cell envelope stress responses and upregulates polysaccharide expression. Mice were immunized with grown with ammonium metavanadate and we developed two IgG2b mAbs, WVDC-0357 and WVDC-0496, directed against the O-antigen lipopolysaccharide of . Functional assays revealed that WVDC-0357 and WVDC-0496 directly reduced the viability of and mediated bacterial agglutination. In a lethal sepsis model of infection, prophylactic treatment of mice with WVDC-0357 and WVDC-0496 at doses as low as 15 mg/kg conferred 100% survival against challenge. In both sepsis and acute pneumonia models of infection, treatment with WVDC-0357 and WVDC-0496 significantly reduced bacterial burden and inflammatory cytokine production post-challenge. Furthermore, histopathological examination of the lungs revealed that WVDC-0357 and WVDC-0496 reduced inflammatory cell infiltration. Overall, our results indicate that mAbs directed against lipopolysaccharide are a promising therapy for the treatment and prevention of infections.