P4-Mediated Antibody Therapy in an Acute Model of Invasive Pneumococcal Disease

• Published in: The Journal of infectious diseases 2012-05, Vol.205 (9), p.1399-1407
• Main Authors: Bangert, Mathieu, Bricio-Moreno, Laura, Gore, Suzanna, Rajam, Gowrisankar, Ades, Edwin W., Gordon, Stephen B., Kadioglu, Aras
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Anti-Bacterial Agents - therapeutic use; Antibodies; Antibodies, Bacterial - immunology; Bacteremia - immunology; Bacteremia - prevention & control; BACTERIA; Bacterial diseases; Biological and medical sciences; Blood; Cell Line; Disease models; Disease Models, Animal; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Human bacterial diseases; Immunization, Passive - methods; Immunoglobulins; Immunoglobulins, Intravenous - immunology; Immunoglobulins, Intravenous - therapeutic use; Immunologic Factors - immunology; Immunologic Factors - therapeutic use; Infections; Infectious diseases; Macrophages; Medical sciences; Mice; Microbiology; Monocytes; Neutrophils; Phagocytes - immunology; Pneumococcal Infections - drug therapy; Pneumococcal Infections - immunology; Receptors; Sepsis - immunology; Sepsis - prevention & control; Staphylococcal infections, streptococcal infections, pneumococcal infections
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jis223

New treatments against severe bacterial infections are needed because the response to antibiotic treatment is slow in acute settings and is becoming less effective owing to the emergence of antibiotic-resistant pathogens. P4-mediated antibody therapy offers a unique treatment strategy that combines exogenous immunoglobulin with the immunoactivating peptide P4. In an acute model of pneumococcal disease, mice were infected with Streptococcus pneumoniae and treated intravenously or intranasally with P4 and intravenous immunoglobulin (IVIG). Survival of P4-IVIG—treated mice increased from 0% to 60% among those that received intravenous treatment and from 0% to 100% among those that received intranasal treatment. Importantly, intranasal administration of P4 at an early stage of infection prevented the onset of bacteremia and sepsis. Increased survival was associated with reduced bacterial burden in affected tissues and with recruitment and activation of professional phagocytes, as manifested by increased expression of Fc-γ receptors. In vitro studies involving P4-stimulated alveolar, peritoneal, and J774.2 murine macrophages showed an increased ability of these immune cells to phagocytose pneumococci independent of capsule. The use of adjunct antibody therapies to treat infectious diseases shows promise.