Novel therapies and vaccines against the human respiratory syncytial virus

Rivera, Claudia A; Gómez, Roberto; Dı́az, Rodrigo; Céspedes, Pablo F.; Espinoza, Javier; González, Pablo A.; Riedel, Claudia A.; Bueno, Susan M.; Kalergis, Alexis M.

doi:10.1517/13543784.2015.1099626

Cited by 14 publications

(20 citation statements)

References 127 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While a number of risk factors have been identified that are associated with the chance of severe RSV infection, the majority of RSV hospitalizations occur in previously healthy children (3). Currently, the only approved RSV-specific therapy is prophylactic treatment with palivizumab (4, 5). However, preventative treatment with palivizumab is restricted to high-risk infants and therefore there is currently no approved method to prevent severe RSV-induced disease in otherwise healthy children (6).…”

Section: Introductionmentioning

confidence: 99%

Altered Treg and cytokine responses in RSV-infected infants

et al. 2016

View full text Add to dashboard Cite

Background: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in children under one year of age in the United States. The host immune response is believed to contribute to RSV-induced disease. We hypothesize that severe RSV infection in infants is mediated by insufficient regulation of the host immune response of regulatory T cells (Tregs) resulting in immunopathology. Methods: Blood and nasal aspirates from 23 RSV-infected and 17 control infants under 1 year of age were collected. Treg frequencies were determined by flow cytometry from peripheral blood mononuclear cells. Analysis of 24 cytokines was measured by multiplex assay on nasal aspirates. Results: We demonstrate that the frequency of activated Tregs is significantly reduced in the peripheral blood of RSV-infected infants compared to age-matched controls. Surprisingly, Th17 related cytokines including IL-1β, IL-17A, and IL-23 were associated with a reduction in clinical symptoms of respiratory distress. In addition, the amount of IL-33 protein in nasal washes, a cytokine important in maintaining Treg homeostasis in mucosal tissues, was decreased in RSV-infected children. Conclusion: These results suggest that decreased Treg numbers and an inability to properly control the host inflammatory response results in severe RSV infection.

show abstract

Section: Introductionmentioning

confidence: 99%

Altered Treg and cytokine responses in RSV-infected infants

et al. 2016

View full text Add to dashboard Cite

show abstract

“…supportive care [33][34][35]. Therefore, novel therapeutics are needed to reduce the severity of RSV infection and limit hospital admissions.…”

Section: Resultsmentioning

confidence: 99%

Chlorogenic Compounds from Coffee Beans Exert Activity against Respiratory Viruses

et al. 2016

View full text Add to dashboard Cite

Chlorogenic acids are secondary metabolites in diverse plants. Some chlorogenic acids extracted from traditional medicinal plants are known for their healing properties, e.g., against viral infections. Also, green coffee beans are a rich source of chlorogenic acids, with 5--caffeoylquinic acid being the most abundant chlorogenic acid in coffee. We previously reported the synthesis of the regioisomers of lactones, bearing different substituents on the quinidic core. Here, 3,4--dicaffeoyl-1,5--quinide and three dimethoxycinnamoyl--quinides were investigated for antiviral activities against a panel of 14 human viruses. Whereas the dimethoxycinnamoyl--quinides did not show any antiviral potency in cytopathogenic effect reduction assays, 3,4--dicaffeoyl-1,5--quinide exerted mild antiviral activity against herpes simplex viruses, adenovirus, and influenza virus. Interestingly, when the compounds were evaluated against respiratory syncytial virus, a potent antiviral effect of 3,4--dicaffeoyl-1,5--quinide was observed against both subtypes of respiratory syncytial virus, with EC values in the submicromolar range. Time-of-addition experiments revealed that this compound acts on an intracellular post-entry replication step. Our data show that 3,4--dicaffeoyl-1,5--quinide is a relevant candidate for lead optimization and further mechanistic studies, and warrants clinical development as a potential anti-respiratory syncytial virus drug.

show abstract

“…One major representative of such ineffective efforts was the Formalin-Inactivated hRSV vaccine (FI-RSV), which actually led to enhanced disease in infants, causing a predisposition to an exacerbated immunopathology due to a strongly biased Th2-like immune response [ 23 , 24 , 25 ]. Currently, a few vaccine prototypes are being developed, with most of them aiming to diminish the Th2-like immune response observed in the hRSV infection [ 26 , 27 , 28 , 29 , 30 ]. Among those, our laboratory has generated a vaccine prototype consisting of a recombinant Mycobacterium bovis Bacillus Calmette–Guérin (BCG) that expresses the hRSV Nucleoprotein (rBCG-N), with promising results such as protective cellular and humoral responses [ 29 , 30 ].…”

Section: General Features Of Human Respiratory Syncytial Virus (Hrmentioning

confidence: 99%

New Insights Contributing to the Development of Effective Vaccines and Therapies to Reduce the Pathology Caused by hRSV

Gálvez

Soto

Kalergis

2017

IJMS

View full text Add to dashboard Cite

Human Respiratory Syncytial Virus (hRSV) is one of the major causes of acute lower respiratory tract infections (ALRTI) worldwide, leading to significant levels of immunocompromisation as well as morbidity and mortality in infants. Its main target of infection is the ciliated epithelium of the lungs and the host immune responses elicited is ineffective at achieving viral clearance. It is thought that the lack of effective immunity against hRSV is due in part to the activity of several viral proteins that modulate the host immune response, enhancing a Th2-like pro-inflammatory state, with the secretion of cytokines that promote the infiltration of immune cells to the lungs, with consequent damage. Furthermore, the adaptive immunity triggered by hRSV infection is characterized by weak cytotoxic T cell responses and secretion of low affinity antibodies by B cells. These features of hRSV infection have meant that, to date, no effective and safe vaccines have been licensed. In this article, we will review in detail the information regarding hRSV characteristics, pathology, and host immune response, along with several prophylactic treatments and vaccine prototypes. We will also expose significant data regarding the newly developed BCG-based vaccine that promotes protective cellular and humoral response against hRSV infection, which is currently undergoing clinical evaluation.

show abstract

Novel therapies and vaccines against the human respiratory syncytial virus

Cited by 14 publications

References 127 publications

Altered Treg and cytokine responses in RSV-infected infants

Altered Treg and cytokine responses in RSV-infected infants

Chlorogenic Compounds from Coffee Beans Exert Activity against Respiratory Viruses

New Insights Contributing to the Development of Effective Vaccines and Therapies to Reduce the Pathology Caused by hRSV

Contact Info

Product

Resources

About