The Anti-Pseudomonas aeruginosa Antibody Panobacumab Is Efficacious on Acute Pneumonia in Neutropenic Mice and Has Additive Effects with Meropenem

Abstract

Pseudomonas aeruginosa (P. aeruginosa) infections are associated with considerable morbidity and mortality in immunocompromised patients due to antibiotic resistance. Therefore, we investigated the efficacy of the anti-P. aeruginosa serotype O11 lipopolysaccharide monoclonal antibody Panobacumab in a clinically relevant murine model of neutropenia induced by cyclophosphamide and in combination with meropenem in susceptible and meropenem resistant P. aeruginosa induced pneumonia. We observed that P. aeruginosa induced pneumonia was dramatically increased in neutropenic mice compared to immunocompetent mice. First, Panobacumab significantly reduced lung inflammation and enhanced bacterial clearance from the lung of neutropenic host. Secondly, combination of Panobacumab and meropenem had an additive effect. Third, Panobacumab retained activity on a meropenem resistant P. aeruginosa strain. In conclusion, the present data established that Panobacumab contributes to the clearance of P. aeruginosa in neutropenic hosts as well as in combination with antibiotics in immunocompetent hosts. This suggests beneficial effects of co-treatment even in immunocompromised individuals, suffering most of the morbidity and mortality of P. aeruginosa infections.

PrtR Homeostasis Contributes to Pseudomonas aeruginosa Pathogenesis and Resistance against Ciprofloxacin

“…In neutropenic patients, other immune cells can contribute to pathogen clearance. A recent study demonstrated that passive immunization with an O-antigen monoclonal antibody protected neutropenic mice from P. aeruginosa infection (37), suggesting that other cells are involved in antibody-mediated clearance of bacteria. Another study demonstrated that monocytes and macrophages are recruited to the infection site and play a major role in clearance of P. aeruginosa in neutropenic mice (38).…”

Targeting bacterial adherence inhibits multidrug-resistant Pseudomonas aeruginosa infection following burn injury

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B cells and antibodies in the defense against Mycobacterium tuberculosis infection

“…At this time, we do not understand enough about the effects of antibody on the inflammatory response to predict if certain patients would benefit from specific immunomodulating antibodies. Such knowledge and understanding would be especially critical when considering and developing post‐exposure and therapeutic vaccines, as well as adjunctive antibody‐based therapy, an approach that has been successful in other infectious and respiratory diseases such as those caused by Pseudomonas aeroginosa and respiratory syncytial virus , and might offer an alternative for difficult to treat multi‐drug resistant TB cases.…”