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J Med Virol. 2018 May 2. doi: 10.1002/jmv.25212. [Epub ahead of print]
Treatment with broadly neutralizing influenza antibodies reduces severity of secondary pneumococcal pneumonia in mice.
van Someren Gr?ve F1,2,3, van der Sluijs KF2, Tuip AM2, Schultz MJ1,2,4, de Jong MD3, Juffermans NP1,2.
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Abstract
BACKGROUND:
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.
METHODS:
Influenza A (H3N2) virus-infected male C57Bl6 mice were treated intravenously with either AT10_002 or a control two days post-infection. Seven days later both groups were infected with Streptococcus pneumoniae, and sacrificed 18 hours later.
RESULTS:
Mice receiving AT10_002 showed less loss of bodyweight compared to controls (+1% vs. -12%, P <0.001), lower viral loads in bronchoalveolar lavage fluids (BALF) (7 versus 194 RNA copies/?l, P <0.001), and reduced bacterial outgrowth in lung homogenates (3.3?10^1 versus 2.5?10^5 colony forming units/mg, P <0.001). The treatment group showed lower pulmonary wet weights, lower cell counts and lower protein levels in BALF compared to controls. Treatment with AT10_002 was associated with lower levels of TNF-α, IL-6, KC and IFN-γ in BALF, and lower IL-6 and KC in lung homogenates.
CONCLUSIONS:
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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
AT10_002; S. pneumoniae; broadly neutralizing antibodies; influenza virus; murine model; secondary infections
PMID: 29718555 DOI: 10.1002/jmv.25212
Treatment with broadly neutralizing influenza antibodies reduces severity of secondary pneumococcal pneumonia in mice.
van Someren Gr?ve F1,2,3, van der Sluijs KF2, Tuip AM2, Schultz MJ1,2,4, de Jong MD3, Juffermans NP1,2.
Author information
Abstract
BACKGROUND:
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.
METHODS:
Influenza A (H3N2) virus-infected male C57Bl6 mice were treated intravenously with either AT10_002 or a control two days post-infection. Seven days later both groups were infected with Streptococcus pneumoniae, and sacrificed 18 hours later.
RESULTS:
Mice receiving AT10_002 showed less loss of bodyweight compared to controls (+1% vs. -12%, P <0.001), lower viral loads in bronchoalveolar lavage fluids (BALF) (7 versus 194 RNA copies/?l, P <0.001), and reduced bacterial outgrowth in lung homogenates (3.3?10^1 versus 2.5?10^5 colony forming units/mg, P <0.001). The treatment group showed lower pulmonary wet weights, lower cell counts and lower protein levels in BALF compared to controls. Treatment with AT10_002 was associated with lower levels of TNF-α, IL-6, KC and IFN-γ in BALF, and lower IL-6 and KC in lung homogenates.
CONCLUSIONS:
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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
AT10_002; S. pneumoniae; broadly neutralizing antibodies; influenza virus; murine model; secondary infections
PMID: 29718555 DOI: 10.1002/jmv.25212