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. 2014 Jul;51(1):143-54.
doi: 10.1165/rcmb.2013-0360OC.

Effects of anti-g and anti-f antibodies on airway function after respiratory syncytial virus infection

Junyan Han  1 , Katsuyuki Takeda, Meiqin Wang, Wanjiang Zeng, Yi Jia, Yoshiki Shiraishi, Masakazu Okamoto, Azzeddine Dakhama, Erwin W Gelfand
Affiliations

Effects of anti-g and anti-f antibodies on airway function after respiratory syncytial virus infection

Junyan Han et al. Am J Respir Cell Mol Biol. 2014 Jul.

Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illnesses in infants worldwide. Both RSV-G and RSV-F glycoproteins play pathogenic roles during infection with RSV. The objective of this study was to compare the effects of anti-RSV-G and anti-RSV-F monoclonal antibodies (mAbs) on airway hyperresponsiveness (AHR) and inflammation after primary or secondary RSV infection in mice. In the primary infection model, mice were infected with RSV at 6 weeks of age. Anti-RSV-G or anti-RSV-F mAbs were administered 24 hours before infection or Day +2 postinfection. In a secondary infection model, mice were infected (primary) with RSV at 1 week (neonate) and reinfected (secondary) 5 weeks later. Anti-RSV-G and anti-RSV-F mAbs were administered 24 hours before the primary infection. Both mAbs had comparable effects in preventing airway responses after primary RSV infection. When given 2 days after infection, anti-RSV-G-treated mice showed significantly decreased AHR and airway inflammation, which persisted in anti-RSV-F-treated mice. In the reinfection model, anti-RSV-G but not anti-RSV-F administered during primary RSV infection in neonates resulted in decreased AHR, eosinophilia, and IL-13 but increased levels of IFN-γ in bronchoalveolar lavage on reinfection. These results support the use of anti-RSV-G in the prevention and treatment of RSV-induced disease.

Keywords: airway; anti–respiratory syncytial virus–F; anti–respiratory syncytial virus–G; inflammation; respiratory syncytial virus.

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Figures

Figure 1.
Figure 1.
Anti–respiratory syncytial virus (RSV)-G and anti–RSV-F monoclonal antibodies (mAbs) had comparable effects in preventing airway responses after primary RSV infection when administered on Day −1. (A) Airway responsiveness to inhaled MCh. (B) Bronchoalveolar lavage (BAL) cellularity. (C) BAL fluid IFN-γ levels. (D) Virus titers in the lung. Results from three independent experiments with 12 mice per group are expressed as mean ± SD. *P < 0.05, **P < 0.01. Eos, eosinophil; Lym, lymphocyte; Mac, macrophage; MCh, methacholine; Neu, neutrophil; PBS, phosphate buffered saline.
Figure 2.
Figure 2.
Anti–RSV-G was effective in preventing AHR and airway inflammation after primary RSV infection when administered 2 days after infection. (A) Airway responsiveness to inhaled MCh. (B) BAL cellularity. (C) BAL fluid IFN-γ levels. (D) Virus titers in the lung. Results from three independent experiments with 12 mice per group are expressed as mean ± SD. *P < 0.05, **P < 0.01.
Figure 3.
Figure 3.
The effects of anti–RSV mAbs on the kinetics of airway responses. (A) Experimental protocol. (B) AHR kinetics after primary RSV infection. (C) BAL cellularity kinetics. (D–F) Airway responsiveness to inhaled MCh (D), BAL cellularity (E), and BAL fluid IFN-γ levels (F) at Day +7 postinfection. (G–I) Airway responsiveness to inhaled MCh (G), BAL cellularity (H), and BAL fluid IFN-γ levels (I) at Day +10 postinfection. (J–L) Airway responsiveness to inhaled MCh (J), BAL cellularity (K), and BAL fluid IFN-γ levels (L) at Day +14 postinfection. The number of CD8+CX3CR1+ T cells in the PBLN (M) and in the lung (N) on Days +7, +10, and +14 were determined by flow cytometry. Results from three independent experiments with 12 mice each group per time point are expressed as mean ± SD. *P < 0.05, **P < 0.01.
Figure 3.
Figure 3.
The effects of anti–RSV mAbs on the kinetics of airway responses. (A) Experimental protocol. (B) AHR kinetics after primary RSV infection. (C) BAL cellularity kinetics. (D–F) Airway responsiveness to inhaled MCh (D), BAL cellularity (E), and BAL fluid IFN-γ levels (F) at Day +7 postinfection. (G–I) Airway responsiveness to inhaled MCh (G), BAL cellularity (H), and BAL fluid IFN-γ levels (I) at Day +10 postinfection. (J–L) Airway responsiveness to inhaled MCh (J), BAL cellularity (K), and BAL fluid IFN-γ levels (L) at Day +14 postinfection. The number of CD8+CX3CR1+ T cells in the PBLN (M) and in the lung (N) on Days +7, +10, and +14 were determined by flow cytometry. Results from three independent experiments with 12 mice each group per time point are expressed as mean ± SD. *P < 0.05, **P < 0.01.
Figure 4.
Figure 4.
Anti–RSV-G mAb reduces the response to secondary RSV infection when administered during neonatal primary infection. (A) Experimental protocol. (B) Airway responsiveness to inhaled MCh. (C) BAL cellularity. (D) BAL fluid IFN-γ levels. (E) BAL fluid IL-13 levels. (F) Virus titers in the lung after primary neonatal RSV infection. Results from three independent experiments with 12 mice per group are expressed as mean ± SD. *P < 0.05, **P < 0.01 indicate significant differences between anti–RSV-G antibody-treated mice and control antibody-treated mice. N/D, not detected.
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