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Vaccines
Special Issues
Pathobiology of Respiratory Syncytial Virus (RSV)
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Pathobiology of Respiratory Syncytial Virus (RSV)

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (29 February 2020) | Viewed by 24510

Special Issue Editors

Prof. Dr. Ralph A. Tripp

E-Mail Website
Guest Editor
Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7387, USA
Interests: RNA viruses; respiratory viruses; epithelial cells; siRNA; CRISPR-Cas; host genes; innate immunity; adaptive immunity; anti-viral immunity
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Paul Mcnamara

E-Mail Website
Guest Editor
Department of Child Health, University of Liverpool, Liverpool, UK
Interests: Bronchiolitis; Cystic Fibrosis; Respiratory disease in children with complex needs

Special Issue Information

Dear Colleagues,

Respiratory Syncytial Virus (RSV), a member of the Paramyxoviridae family, is the leading cause of lower respiratory tract illness in infants and also affects the elderly and the immune-compromised. RSV apically infects ciliated respiratory epithelial cells often leading to bronchiolitis, characterized by mucus in the airways, sloughed epithelial cell debris, and abundant neutrophils. Airway mucus contributes to pulmonary obstruction, but the mechanisms of RSV-induced mucus expression remain unclear. Though mice are semi-permissive for RSV replication, they have been the model of choice because they nonetheless contribute to a better mechanistic understanding of the immune response to RSV. Immune and disease correlates are under investigation in animal models and humans as there is currently no approved RSV vaccine, and therapeutics are limited. This Special Issue on “Pathobiology of Respiratory Syncytial Virus (RSV)” will cover all aspects of RSV pathogenesis, RSV immunity, RSV modulation of host responses, and RSV vaccines and antivirals.

Prof. Dr. Ralph A. Tripp
Prof. Dr. Paul Mcnamara
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • respiratory syncytial virus
  • lung disease
  • airways
  • bronchiolitis
  • vaccine
  • therapeutics
  • innate immune response
  • adaptive immune response

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Published Papers (6 papers)

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Editorial

Jump to: Research, Review, Other

2 pages, 143 KiB  
Editorial
Pathobiology of Respiratory Syncytial Virus (RSV)
by Ralph A. Tripp and Paul S. McNamara
Vaccines 2020, 8(3), 367; https://doi.org/10.3390/vaccines8030367 - 9 Jul 2020
Viewed by 2126
Abstract
Respiratory Syncytial Virus (RSV) is the leading cause of lower respiratory tract illness in infants and affects the elderly and the immune-compromised [...] Full article
(This article belongs to the Special Issue Pathobiology of Respiratory Syncytial Virus (RSV))

Research

Jump to: Editorial, Review, Other

13 pages, 829 KiB  
Article
Antibody Response to the Furin Cleavable Twenty-Seven Amino Acid Peptide (p27) of the Fusion Protein in Respiratory Syncytial Virus (RSV) Infected Adult Hematopoietic Cell Transplant (HCT) Recipients
by Xunyan Ye, Wanderson Cabral de Rezende, Obinna Patrick Iwuchukwu, Vasanthi Avadhanula, Laura L. Ferlic-Stark, Kirtida D. Patel, Felipe-Andres Piedra, Dimpy P. Shah, Roy F. Chemaly and Pedro A. Piedra
Vaccines 2020, 8(2), 192; https://doi.org/10.3390/vaccines8020192 - 21 Apr 2020
Cited by 9 | Viewed by 3335
Abstract
Background: Cleavage of the inactive precursor fusion protein (F0) of respiratory syncytial virus (RSV) at two furin-recognition sites is required for membrane fusion activity, and the cleavage releases the twenty-seven amino acid peptide (p27). However, a recent study shows that p27 was an [...] Read more.
Background: Cleavage of the inactive precursor fusion protein (F0) of respiratory syncytial virus (RSV) at two furin-recognition sites is required for membrane fusion activity, and the cleavage releases the twenty-seven amino acid peptide (p27). However, a recent study shows that p27 was an immunodominant epitope in RSV infected children, indicating that p27 was recognized as an immunogen. In the present study, we investigated the immunogenicity of p27 in an immunocompromised population of adults by measuring serum and mucosal antibody responses to p27 in samples from adult hematopoietic cell transplant (HCT) recipients. Methods: We prospectively enrolled a cohort of RSV infected HCT recipients. Serum and nasal-wash samples were obtained within the first week of RSV infection (acute) and 3 to 5 weeks post-infection (convalescent). We quantified the serum and mucosal IgG and IgA anti-p27 antibodies by a RSV/A p27 peptide enzyme-linked immunosorbent assay (ELISA) and serum and mucosal p27 like antibodies (P27LA) by a p27 competitive antibody (P27CA) assay. Results: The lower limit of detection for the ELISA and P27CA assays was 0.2 and 50 ng/mL, respectively with no cross-reaction detected with a panel of monoclonal antibodies targeting pre-fusion and post-fusion antigenic sites. P27 antibodies were detected at nanogram concentration in sera and nasal washes in the majority of RSV infected HCT recipients. However, there was no significant difference in the geometric mean antibody concentrations between the acute and convalescent sera (except for serum P27LA), between HCT recipients who shed RSV <14 days and ≥14 days, as well as between RSV/A and RSV/B infected HCT recipients. In addition, approximately 30% of HCT recipients had a 4-fold or greater decrease in mucosal IgG and IgA anti-p27 antibodies during viral clearance. Conclusion: In conclusion, in RSV naturally infected adult HCT recipients, the antibodies against p27 were detectable in both serum and nasal wash samples with higher concentration in serum than that in nasal washes. However, nearly 30% of RSV infected HCT recipients had a significant decrease in their mucosal anti-p27 antibody, suggesting that IgG and IgA anti-p27 antibodies were binding to either free viruses or RSV infected cells containing p27, and that anti-p27 antibodies in the respiratory tract were part of the mucosal antibody response in controlling RSV infection. Full article
(This article belongs to the Special Issue Pathobiology of Respiratory Syncytial Virus (RSV))
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15 pages, 4621 KiB  
Article
Comparisons of Antibody Populations in Different Pre-Fusion F VLP-Immunized Cotton Rat Dams and Their Offspring
by Lori M. Cullen, Marina S. Boukhvalova, Jorge C. G. Blanco and Trudy G. Morrison
Vaccines 2020, 8(1), 133; https://doi.org/10.3390/vaccines8010133 - 18 Mar 2020
Cited by 6 | Viewed by 3019
Abstract
Respiratory syncytial virus (RSV) infection poses a significant risk for infants. Since the direct vaccination of infants is problematic, maternal vaccination may provide a safer, more effective approach to their protection. In the cotton rat (CR) model, we have compared the immunization of [...] Read more.
Respiratory syncytial virus (RSV) infection poses a significant risk for infants. Since the direct vaccination of infants is problematic, maternal vaccination may provide a safer, more effective approach to their protection. In the cotton rat (CR) model, we have compared the immunization of pregnant CR dams with virus-like particles assembled with the prototype mutation stabilized pre-fusion F protein, DS-Cav1, as well two alternative mutation stabilized pre-fusion proteins (UC-2 F, UC-3 F) and showed that the alternative pre-fusion F VLPs protected the offspring of immunized dams significantly better than DS-Cav1 F VLPs (Blanco, et al. J. Virol. 93: e00914). Here, we have addressed the reasons for this increased protection by characterizing the specificities of antibodies in the sera of both immunized dams and their offspring. The approach was to measure the levels of total anti-pre-F IgG serum antibodies that would block the binding of representative pre-fusion specific monoclonal antibodies to soluble pre-fusion F protein targets. Strikingly, we found that the sera in most offspring of DS-Cav1 F VLP-immunized dams had no mAb D25-blocking antibodies, although their dams had robust levels. In contrast, all offspring of UC-3 F VLP-immunized dams had robust levels of these D25-blocking antibodies. Both sets of pup sera had significant levels of mAb AM14-blocking antibodies, indicating that all pups received maternal antibodies. A lack of mAb D25-blocking antibodies in the offspring of DS-Cav1 F VLP-immunized dams may account for the lower protection of their pups from challenge compared to the offspring of UC-3 F VLP-immunized dams. Full article
(This article belongs to the Special Issue Pathobiology of Respiratory Syncytial Virus (RSV))
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Review

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10 pages, 270 KiB  
Review
A Durable Relationship: Respiratory Syncytial Virus Bronchiolitis and Asthma past Their Golden Anniversary
by Ignacio Esteban, Renato T. Stein and Fernando P. Polack
Vaccines 2020, 8(2), 201; https://doi.org/10.3390/vaccines8020201 - 26 Apr 2020
Cited by 21 | Viewed by 3755
Abstract
Numerous preventive strategies against respiratory syncytial virus (RSV) are undergoing late stage evaluation in humans and, in addition to their intended benefit for acute illness, may impact long term consequences of infection in infants. Severe RSV infection has been repeatedly associated in the [...] Read more.
Numerous preventive strategies against respiratory syncytial virus (RSV) are undergoing late stage evaluation in humans and, in addition to their intended benefit for acute illness, may impact long term consequences of infection in infants. Severe RSV infection has been repeatedly associated in the literature with long term complications, including impaired lung function, recurrent wheezing, and asthma. However, whether RSV lower respiratory tract infection (LRTI) causally affects the odds for developing wheezing and/or asthma during childhood requires further study, and the biological mechanisms underlying this hypothetical progression from viral illness to chronic lung disease are poorly characterized. In this review, we summarize the literature exploring the association between RSV LRTI in infancy and subsequent recurrent wheezing and pediatric asthma. Full article
(This article belongs to the Special Issue Pathobiology of Respiratory Syncytial Virus (RSV))
16 pages, 680 KiB  
Review
Function and Modulation of Type I Interferons during Respiratory Syncytial Virus Infection
by Laura M. Stephens and Steven M. Varga
Vaccines 2020, 8(2), 177; https://doi.org/10.3390/vaccines8020177 - 10 Apr 2020
Cited by 20 | Viewed by 6899
Abstract
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory infections in infants and young children, accounting for an estimated 3 million hospitalizations annually worldwide. Despite the major health burden, there is currently no licensed RSV vaccine. RSV is recognized by a [...] Read more.
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory infections in infants and young children, accounting for an estimated 3 million hospitalizations annually worldwide. Despite the major health burden, there is currently no licensed RSV vaccine. RSV is recognized by a range of cellular receptors including both toll-like receptors (TLR) and retinoic acid-inducible gene-I-like receptors (RIG-I). This interaction initiates signaling through mitochondrial antiviral signaling (MAVS) and interferon regulatory factor (IRF) proteins, resulting in the induction of type I interferons (IFN). Early viral control is mediated by either IFN-α or IFN-β signaling through the IFN receptor (IFNAR), inducing the production of antiviral interferon-stimulating genes (ISGs). Type I IFNs also initiate the early production of proinflammatory cytokines including interleukin 6 (IL-6), tumor necrosis factor (TNF), and IFN-γ. Type I IFN levels correlate with age, and inadequate production may be a critical factor in facilitating the increased RSV disease severity observed in infants. Here, we review the current literature on the function of type I IFNs in RSV pathogenesis, as well as their involvement in the differential immune responses observed in infants and adults. Full article
(This article belongs to the Special Issue Pathobiology of Respiratory Syncytial Virus (RSV))
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Other

6 pages, 182 KiB  
Commentary
Original Antigenic Sin and Respiratory Syncytial Virus Vaccines
by Ralph A. Tripp and Ultan F. Power
Vaccines 2019, 7(3), 107; https://doi.org/10.3390/vaccines7030107 - 6 Sep 2019
Cited by 12 | Viewed by 4419
Abstract
The original antigenic sin (OAS) theory considers the outcome of the first encounter with an antigen. It favors a memory response to the original antigen upon exposure to a similar or related antigen, and includes both positive and negative impacts of past exposure [...] Read more.
The original antigenic sin (OAS) theory considers the outcome of the first encounter with an antigen. It favors a memory response to the original antigen upon exposure to a similar or related antigen, and includes both positive and negative impacts of past exposure on the memory response to challenge, and, in particular, on vaccine efficacy. This phenomenon is closely linked with imprinting and the hierarchical nature of immune responses to previously encountered antigens. The focus of this commentary centers on the potential role of OAS or immunological imprinting on respiratory syncytial virus memory responses. Full article
(This article belongs to the Special Issue Pathobiology of Respiratory Syncytial Virus (RSV))
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