Treatment with broadly neutralizing influenza antibodies reduces severity of secondary pneumococcal pneumonia in mice.

Autor: van Someren Gréve F; Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands.; Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, Amsterdam, The Netherlands.; Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands., van der Sluijs KF; Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, Amsterdam, The Netherlands., Tuip AM; Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, Amsterdam, The Netherlands., Schultz MJ; Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands.; Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, Amsterdam, The Netherlands.; Faculty of Tropical Medicine, Mahidol Oxford Research Unit (MORU), Mahidol University, Bangkok, Thailand., de Jong MD; Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands., Juffermans NP; Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands.; Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Journal of medical virology [J Med Virol] 2018 Sep; Vol. 90 (9), pp. 1431-1437. Date of Electronic Publication: 2018 Jun 12.
DOI: 10.1002/jmv.25212
Abstrakt: Secondary bacterial pneumonia is a frequent complication of influenza, associated with high morbidity and mortality. We hypothesized that treatment with neutralizing influenza A antibody AT10_002 protects against severe secondary pneumococcal infection in a mouse model of influenza A infection. Influenza A (H3N2) virus-infected male C57Bl6 mice were treated intravenously with either AT10_002 or a control 2 days postinfection. Seven days later, both groups were infected with Streptococcus pneumoniae and killed 18 hours later. Mice receiving AT10_002 showed less loss of bodyweight compared with controls (+1% vs -12%, P < .001), lower viral loads in bronchoalveolar lavage fluids (BALFs) (7 vs 194 RNA copies per µL; P < .001), and reduced bacterial outgrowth in lung homogenates (3.3 × 10 1 vs 2.5 × 10 5 colony-forming units per mg; P < .001). The treatment group showed lower pulmonary wet weights, lower cell counts, and lower protein levels in BALF compared with controls. Treatment with AT10_002 was associated with lower levels of tumor necrosis factor-α, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (KC), and interferon-γ in BALF and lower IL-6 and KC in lung homogenates. Treatment with anti-influenza antibody AT10_002 is associated with reduced weight loss, viral load, bacterial outgrowth, and lung injury in a murine model of secondary pneumococcal pneumonia following influenza infection.
(© 2018 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.)
Databáze: MEDLINE
Externí odkaz: