Therapeutic targeting of respiratory syncytial virus G-protein

Kauvar, Lawrence M.; Harcourt, Jennifer L.; Haynes, Lia M.; Tripp, Ralph A.

doi:10.2217/imt.10.53

Cited by 34 publications

(37 citation statements)

References 51 publications

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“…Moreover, palivizumab has not been effective as postinfection therapy and may even be deleterious when administered postinfection (5). Emerging data support targeting of the G glycoprotein (3). In the present study, comparisons of anti-RSV-F (palivizumab) and anti-RSV-G were examined in both prophylactic and postinfection approaches as well as in a secondary, reinfection model.…”

Section: Discussionmentioning

confidence: 97%

“…Repeated efforts to develop a vaccine against RSV have failed, and therapeutic options are limited (2). The development of new therapeutic or prophylactic agents remains a major challenge and clinical priority (3).…”

Section: Clinical Relevancementioning

confidence: 99%

“…Over the past decade, with recognition of its enhancing role in the pathogenesis of RSV infection, targeting G glycoprotein has gained attention (3). In mice, G glycoprotein has been linked to the induction of Th2 cytokines (6,7) and to causing RSV-induced eosinophilia in a vaccine-enhanced disease model (8).…”

Section: Clinical Relevancementioning

confidence: 99%

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

Han

Takeda

Wang

et al. 2014

Am J Respir Cell Mol Biol

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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.

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Section: Discussionmentioning

confidence: 97%

Section: Clinical Relevancementioning

confidence: 99%

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

Han

Takeda

Wang

et al. 2014

Am J Respir Cell Mol Biol

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“…In addition to NS1 and NS2, the G-protein itself seems to play a major role in immune evasion of RSV. This protein is highly glycosylated, which may impede immune recognition, and its high variability allows easy escape from neutralising antibodies [43]. Furthermore, during viral replication, a soluble form of G-protein (sG-protein) is released and binds RSV-specific antibodies, thus, reducing the concentrations available for RSV neutralisation [44].…”

Section: Rsv Infection and Host Immune Responsementioning

confidence: 99%

Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing

2014

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There is evidence that respiratory viruses play a key role in the development and exacerbation of obstructive respiratory diseases in children. This review attempts to juxtapose the separate profiles and prototypes of pathogenenetic mechanisms represented by the two most common amongst such viruses: respiratory syncytial virus (RSV) and human rhinovirus (HRV).RSV represents the most common agent of severe airway disease in infants and young children, and is predominant in winter months. Large epidemiological studies have revealed an unequivocal relationship between RSV infection and subsequent wheezing into childhood, thought to be related to long-term changes in neuroimmune control of the airways rather than allergic sensitisation.HRV is a highly diverse group of viruses that affect subjects of all ages, is ubiquitous and occurs yearround. In contrast to RSV, infections with HRV cause minimal cytotoxicity but induce a rapid production of cytokines and chemokines with amplification of the inflammatory response. The susceptibility to HRVinduced bronchiolitis and subsequent wheezing appears to be linked to individual predisposition since it is often associated with a family or personal history of asthma/atopy.Thus, RSV probably serves as an "inducer" rather than a "trigger". Conversely, HRVs seem to serve as a "trigger" rather than an "inducer" in predisposed individuals. @ERSpublications Comprehensive overview of the different roles of RSV and HRV in the pathogenesis of recurrent wheezing in childhood

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“…It is becoming evident that the G protein also plays a substantial role in evading the host immune response to infection (27,28) as well as inducing immune responses that contribute to disease. For example, the G protein is associated with a lower frequency of interferon gamma (IFN-␥) and a higher frequency of interleukin-5 (IL-5)-and IL-6-expressing T cells (29) and alterations in the production of cytokines in infected mice (30).…”

mentioning

confidence: 99%

Prophylaxis with a Respiratory Syncytial Virus (RSV) Anti-G Protein Monoclonal Antibody Shifts the Adaptive Immune Response to RSV rA2-line19F Infection from Th2 to Th1 in BALB/c Mice

Boyoglu-Barnum

Chirkova

Todd

et al. 2014

J Virol

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Respiratory syncytial virus (RSV) is IMPORTANCEThe data in this report suggest that the RSV G protein not only contributes to disease but also dampens the host immune response to infection. Both effects of G likely contribute to difficulties in achieving an effective vaccine. The ability of MAb 131-2G to block these effects of G suggests that inducing antibodies similar to 131-2G should prevent disease and enhance the adaptive immune response with later RSV infection. The fact that 131-2G binds to the 13-amino-acid region conserved among all strains and that flanking sequences are conserved within group A or group B strains simplifies the task of developing a vaccine to induce 131-2G-like antibodies. If our findings in mice apply to humans, then including the 131-2G binding region of G in a vaccine should improve its safety and efficacy.

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Therapeutic targeting of respiratory syncytial virus G-protein

Cited by 34 publications

References 51 publications

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

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

Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing

Prophylaxis with a Respiratory Syncytial Virus (RSV) Anti-G Protein Monoclonal Antibody Shifts the Adaptive Immune Response to RSV rA2-line19F Infection from Th2 to Th1 in BALB/c Mice

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