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

摘要

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.