Effects of Anti-G and Anti-F Antibodies on Airway Function after Respiratory Syncytial Virus Infection

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 12 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-g in bronchoalveolar lavage on reinfection. These results support the use of anti-RSV-G in the prevention and treatment of RSV-induced disease.

An anti-G protein monoclonal antibody treats RSV disease more effectively than an anti-F monoclonal antibody in BALB/c mice

“…This was evident despite 143-6C's slightly greater effect on virus replication as indicated by pulmonary virus titer and RSV RNA levels. These findings support and extend the findings described by Han et al (Han et al, 2014). In that study, RSV-infected mice treated on 2 day pi with a humanized anti–G mAb similar to 131-2G had significantly less methacholine induced airway resistance than untreated mice at days 7-10 pi.…”

“…Interestingly, 131-2G decreased pulmonary inflammation more effectively than an anti-F mAb, 143-6C, that reacts at the same antigenic site as palivizumab and like palivizumab both neutralizes RSV and inhibits RSV fusion (Anderson et al, 1988; Boyoglu-Barnum et al, 2014; DeVincenzo et al, 2014). Han et al recently reported that a humanized mAb that reacts at the same antigenic site as 131-2G also decreases airway reactivity induced by methacholine challenge and does this much more effectively than palivizumab (Han et al, 2014). These data suggest that an anti-G mAb like 131-2G might be more effective than anti-F neutralizing antibodies in treating active RSV infection.…”

Respiratory Syncytial Virus: Targeting the G Protein Provides a New Approach for an Old Problem

“…The TRL3D3 MAb, whose affinity is high enough to neutralize the soluble G protein, has also shown direct antiviral activity with improved potency over palivizumab in mice (38). Consistent with the ex vivo effects of MAbs against RSV F or G proteins on IFN production, treatment with palivizumab was associated with increased airway inflammation in a mouse model, whereas TRL3D3 suppressed it (49). The lack of robust, long-lasting immunity following RSV infection results in frequent reinfection.…”

Mutating the CX3C Motif in the G Protein Should Make a Live Respiratory Syncytial Virus Vaccine Safer and More Effective

“…In in vitro studies, the RSV G protein has been noted to stimulate AEC responses and to dampen macrophage and dendritic cell responses (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). In vivo in mice, RSV G protein has been associated with increased weight loss, numbers of pulmonary inflammatory cells, levels of pulmonary mucus and Th2 cytokines, airway obstruction, and enhanced respiratory disease in RSV-challenged, FI-RSVvaccinated mice (18,20,21,26,31,(48)(49)(50)(51). Studies in mice have also shown that it enhances cytotoxic T cell responses (44,52), modifies adaptive immune responses (31), and, when given intravenously, suppresses respiratory rates (22).…”