Respiratory Syncytial Virus (RSV) Diseases

Rna Virus ◽

Passive Immunization ◽

Active Immunization ◽

F Protein ◽

Hospitalization Rates ◽

Syncytial Virus ◽

Repeated Infections ◽

Long Acting ◽

Underlying Diseases

The respiratory syncytial virus (RSV) is an RNA virus that causes annual ARI outbreaks during winter with mild URTI in the general population, but with severe LRTI particularly among young children (bronchiolitis), patients with underlying diseases and people >65 years of age. RSV does not induce a long-lasting protective immunity and repeated infections throughout life are the norm. Basically, all children have been infected by 2 years of age and of those hospitalized, >50% are <3 months and 75% are <6 months of age. The overall CFR is 1/500. For adults ≥65 years, RSV hospitalization rates are 90–250/105. There is no specific therapy, general preventive measures include general hygiene and isolation/separation of patients. A monoclonal anti-F-protein antibody is available for passive immunization of selected high-risk children. It requires monthly injections, comes at a high cost and has limited efficacy (50% against RSV hospitalization). Active immunization failed in the past, probably as the post-fusion conformation of the F-protein was used. Long-acting monoclonal antibodies (for infants) as well as stabilized pre-fusion F-protein vaccines (for immunization of pregnant women, children, older adults) produced on various platforms are in late stages of clinical development.

Prevention of respiratory syncytial virus infections

Revista do Hospital das Clínicas ◽

10.1590/s0041-87812001000300004 ◽

2001 ◽

Vol 56 (3) ◽

pp. 79-90 ◽

Cited By ~ 3

Author(s):

Lucia Ferro Bricks

Keyword(s):

Bronchopulmonary Dysplasia ◽

Passive Immunization ◽

Respiratory Illness ◽

Active Immunization ◽

Infants And Children ◽

Virus Infections ◽

Medical Problems ◽

Respiratory Syncytial Virus Infections ◽

Respiratory syncytial virus is the most important cause of viral lower respiratory illness in infants and children worldwide. By the age of 2 years, nearly every child has become infected with respiratory syncytial virus and re-infections are common throughout life. Most infections are mild and can be managed at home, but this virus causes serious diseases in preterm children, especially those with bronchopulmonary dysplasia. Respiratory syncytial virus has also been recognized as an important pathogen in people with immunossupressive and other underlying medical problems and institutionalizated elderly, causing thousands of hospitalizations and deaths every year. The burden of these infections makes the development of vaccines for respiratory syncytial virus highly desirable, but the insuccess of a respiratory syncytial virus formalin-inactivated vaccine hampered the progress in this field. To date, there is no vaccine available for preventing respiratory syncytial virus infections, however, in the last years, there has been much progress in the understanding of immunology and immunopathologic mechanisms of respiratory syncytial virus diseases, which has allowed the development of new strategies for passive and active prophylaxis. In this article, the author presents a review about novel approaches to the prevention of respiratory syncytial virus infections, such as: passive immunization with human polyclonal intravenous immune globulin and humanized monoclonal antibodies (both already licensed for use in premature infants and children with bronchopulmonary dysplasia), and many different vaccines that are potential candidates for active immunization against respiratory syncytial virus.

1719. Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1897 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S843-S843

Author(s):

John M McLaughlin ◽

Farid L Khan ◽

Heinz-Josef Schmitt ◽

Yasmeen Agosti ◽

Luis Jodar ◽

...

Keyword(s):

Public Health ◽

Active Surveillance ◽

Meta Analysis ◽

The United States ◽

Administrative Claims ◽

Prevention Strategies ◽

Hospitalization Rates ◽

Syncytial Virus ◽

The Impact

Abstract Background Understanding the true magnitude of infant respiratory syncytial virus (RSV) burden is critical for determining the potential public-health benefit of RSV prevention strategies. Although global reviews of infant RSV burden exist, none have summarized data from the United States or evaluated how RSV burden estimates are influenced by variations in study design. Methods We performed a systematic literature review and meta-analysis of studies describing RSV-associated hospitalization rates among US infants. We also examined the impact of key study characteristics on these estimates. Results After review of 3058 articles through January 2020, we identified 25 studies with 31 unique estimates of RSV-associated hospitalization rates. Among US infants < 1 year of age, annual rates ranged from 8.4 to 40.8 per 1000 with a pooled rate= 19.4 (95%CI= 17.9–20.9). Study type was associated with RSV hospitalization rates (P =.003), with active surveillance studies having pooled rates per 1000 (11.1; 95%CI: 9.8–12.3) that were half that of studies based on administrative claims (21.4; 95%CI: 19.5–23.3) or modeling approaches (23.2; 95%CI: 20.2–26.2). Conclusion Applying the pooled rates identified in our review to the 2020 US birth cohort suggests that 73,680 to 86,020 RSV-associated infant hospitalizations occur each year. To date, public-health officials have used conservative estimates from active surveillance as the basis for defining US infant RSV burden. The full range of RSV-associated hospitalization rates identified in our review better characterizes the true RSV burden in infants and can better inform future evaluations of RSV prevention strategies. Disclosures John M. McLaughlin, PhD, Pfizer (Employee, Shareholder) Farid L. Khan, MPH, Pfizer (Employee, Shareholder) Heinz-Josef Schmitt, MD, Pfizer (Employee, Shareholder) Yasmeen Agosti, MD, Pfizer (Employee, Shareholder) Luis Jodar, PhD, Pfizer (Employee, Shareholder) Eric Simões, MD, Pfizer (Consultant, Research Grant or Support) David L. Swerdlow, MD, Pfizer (Employee, Shareholder)

Shifting immunodominance pattern of two cytotoxic T-lymphocyte epitopes in the F glycoprotein of the Long strain of respiratory syncytial virus

Journal of General Virology ◽

10.1099/vir.0.80219-0 ◽

2004 ◽

Vol 85 (11) ◽

pp. 3229-3238 ◽

Cited By ~ 28

Author(s):

Carolina Johnstone ◽

Patricia de León ◽

Francisco Medina ◽

José A. Melero ◽

Blanca García-Barreno ◽

...

Keyword(s):

Vaccinia Virus ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Recombinant Vaccinia Virus ◽

Recombinant Vaccinia ◽

F Protein ◽

Syncytial Virus ◽

Lymphocyte Responses

Human respiratory syncytial virus (RSV) is a major cause of respiratory infection in children and in the elderly. The RSV fusion (F) glycoprotein has long been recognized as a vaccine candidate as it elicits cytotoxic T-lymphocyte (CTL) and antibody responses. Two murine H-2Kd-restricted CTL epitopes (F85–93 and F92–106) are known in the F protein of the A2 strain of RSV. F-specific CTL lines using BCH4 fibroblasts that are persistently infected with the Long strain of human RSV as stimulators were generated, and it was found that in this strain only the F85–93 epitope is conserved. Motif based epitope prediction programs and an F2 chain deleted F protein encoded in a recombinant vaccinia virus enabled identification of a new epitope in the Long strain, F249–258, which is presented by Kd as a 9-mer (TYMLTNSEL) or a 10-mer (TYMLTNSELL) peptide. The results suggest that the 10-mer might be a naturally processed endogenous Kd ligand. The CD8+ T-lymphocyte responses to epitopes F85–93 and F249–258 present in the F protein of RSV Long were found to be strongly skewed to F85–93 in in vitro multispecific CTL lines and in vivo during a secondary response to a recombinant vaccinia virus that expresses the entire F protein. However, no hierarchy in CD8+ T-lymphocyte responses to F85–93 and F249–258 epitopes was observed in vivo during a primary response.

Immunogenicity and efficacy of codon optimized DNA vaccines encoding the F-protein of respiratory syncytial virus

Vaccine ◽

10.1016/j.vaccine.2007.07.025 ◽

2007 ◽

Vol 25 (41) ◽

pp. 7271-7279 ◽

Cited By ~ 47

Author(s):

Nicola Ternette ◽

Bettina Tippler ◽

Klaus Überla ◽

Thomas Grunwald

Keyword(s):

Dna Vaccines ◽

F Protein ◽

Reduction of Respiratory Syncytial Virus (RSV) in Tracheal Aspirates in Intubated Infants by Use of Humanized Monoclonal Antibody to RSV F Protein

The Journal of Infectious Diseases ◽

10.1086/314523 ◽

1998 ◽

Vol 178 (6) ◽

pp. 1555-1561 ◽

Cited By ~ 148

Author(s):

Richard Malley ◽

John DeVincenzo ◽

Octavio Ramilo ◽

Penelope H. Dennehy ◽

H. Cody Meissner ◽

...

Keyword(s):

Monoclonal Antibody ◽

F Protein ◽

Humanized Monoclonal Antibody ◽

Syncytial Virus ◽

Tracheal Aspirates

Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate

Journal of Virology ◽

10.1128/jvi.01373-15 ◽

2015 ◽

Vol 89 (18) ◽

pp. 9499-9510 ◽

Cited By ~ 37

Author(s):

Bo Liang ◽

Sonja Surman ◽

Emerito Amaro-Carambot ◽

Barbora Kabatova ◽

Natalie Mackow ◽

...

Keyword(s):

Clinical Evaluation ◽

Genetic Stability ◽

Vaccine Candidate ◽

Early Passage ◽

F Protein ◽

Syncytial Virus ◽

Human Parainfluenza Virus ◽

Type 3

ABSTRACTRespiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are the first and second leading viral agents of severe respiratory tract disease in infants and young children worldwide. Vaccines are not available, and an RSV vaccine is particularly needed. A live attenuated chimeric recombinant bovine/human PIV3 (rB/HPIV3) vector expressing the RSV fusion (F) glycoprotein from an added gene has been under development as a bivalent vaccine against RSV and HPIV3. Previous clinical evaluation of this vaccine candidate suggested that increased genetic stability and immunogenicity of the RSV F insert were needed. This was investigated in the present study. RSV F expression was enhanced 5-fold by codon optimization and by modifying the amino acid sequence to be identical to that of an early passage of the original clinical isolate. This conferred a hypofusogenic phenotype that presumably reflects the original isolate. We then compared vectors expressing stabilized prefusion and postfusion versions of RSV F. In a hamster model, prefusion F induced increased quantity and quality of RSV-neutralizing serum antibodies and increased protection against wild-type (wt) RSV challenge. In contrast, a vector expressing the postfusion F was less immunogenic and protective. The genetic stability of the RSV F insert was high and was not affected by enhanced expression or the prefusion or postfusion conformation of RSV F. These studies provide an improved version of the previously well-tolerated rB/HPIV3-RSV F vaccine candidate that induces a superior RSV-neutralizing serum antibody response.IMPORTANCERespiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are two major causes of pediatric pneumonia and bronchiolitis. The rB/HPIV3 vector expressing RSV F protein is a candidate bivalent live vaccine against HPIV3 and RSV. Previous clinical evaluation indicated the need to increase the immunogenicity and genetic stability of the RSV F insert. Here, we increased RSV F expression by codon optimization and by modifying the RSV F amino acid sequence to conform to that of an early passage of the original isolate. This resulted in a hypofusogenic phenotype, which likely represents the original phenotype before adaptation to cell culture. We also included stabilized versions of prefusion and postfusion RSV F protein. Prefusion RSV F induced a larger quantity and higher quality of RSV-neutralizing serum antibodies and was highly protective. This provides an improved candidate for further clinical evaluation.

Characterization of Pre-F-GCN4t, a Modified Human Respiratory Syncytial Virus Fusion Protein Stabilized in a Noncleaved Prefusion Conformation

Journal of Virology ◽

10.1128/jvi.02437-16 ◽

2017 ◽

Vol 91 (13) ◽

Cited By ~ 18

Author(s):

Normand Blais ◽

Martin Gagné ◽

Yoshitomo Hamuro ◽

Patrick Rheault ◽

Martine Boyer ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Human Respiratory Syncytial Virus ◽

Vaccine Antigen ◽

Significant Advance ◽

F Protein ◽

ABSTRACT The human respiratory syncytial virus (hRSV) fusion (F) protein is considered a major target of the neutralizing antibody response to hRSV. This glycoprotein undergoes a major structural shift from the prefusion (pre-F) to the postfusion (post-F) state at the time of virus-host cell membrane fusion. Recent evidences suggest that the pre-F state is a superior target for neutralizing antibodies compared to the post-F state. Therefore, for vaccine purposes, we have designed and characterized a recombinant hRSV F protein, called Pre-F-GCN4t, stabilized in a pre-F conformation. To show that Pre-F-GCN4t does not switch to a post-F conformation, it was compared with a recombinant post-F molecule, called Post-F-XC. Pre-F-GCN4t was glycosylated and trimeric and displayed a conformational stability different from that of Post-F-XC, as shown by chemical denaturation. Electron microscopy analysis suggested that Pre-F-GCN4t adopts a lollipop-like structure. In contrast, Post-F-XC had a typical elongated conical shape. Hydrogen/deuterium exchange mass spectrometry demonstrated that the two molecules had common rigid folding core and dynamic regions and provided structural insight for their biophysical and biochemical properties and reactivity. Pre-F-GCN4t was shown to deplete hRSV-neutralizing antibodies from human serum more efficiently than Post-F-XC. Importantly, Pre-F-GCN4t was also shown to bind D25, a highly potent monoclonal antibody specific for the pre-F conformation. In conclusion, this construct presents several pre-F characteristics, does not switch to the post-F conformation, and presents antigenic features required for a protective neutralizing antibody response. Therefore, Pre-F-GCN4t can be considered a promising candidate vaccine antigen. IMPORTANCE Human respiratory syncytial virus (RSV) is a global leading cause of infant mortality and adult morbidity. The development of a safe and efficacious RSV vaccine remains an important goal. The RSV class I fusion (F) glycoprotein is considered one of the most promising vaccine candidates, and recent evidences suggest that the prefusion (pre-F) state is a superior target for neutralizing antibodies. Our study presents the physicochemical characterization of Pre-F-GCN4t, a molecule designed to be stabilized in the pre-F conformation. To confirm its pre-F conformation, Pre-F-GCN4t was analyzed in parallel with Post-F-XC, a molecule in the post-F conformation. Our results show that Pre-F-GCN4t presents characteristics of a stabilized pre-F conformation and support its use as an RSV vaccine antigen. Such an antigen may represent a significant advance in the development of an RSV vaccine.

The respiratory syncytial virus (RSV) prefusion F‐protein functional antibody repertoire in adult healthy donors

EMBO Molecular Medicine ◽

10.15252/emmm.202114035 ◽

2021 ◽

Author(s):

Emanuele Andreano ◽

Ida Paciello ◽

Monia Bardelli ◽

Simona Tavarini ◽

Chiara Sammicheli ◽

...

Keyword(s):

Antibody Repertoire ◽

F Protein ◽

Healthy Donors ◽

Detection of Respiratory Syncytial Virus in Nasopharyngeal Secretions by 24-Well Plate Precentrifugation Assay Using a Monoclonal Antibody Against F Protein

Archives of Medical Research ◽

10.1016/s0188-4409(99)00068-5 ◽

2000 ◽

Vol 31 (1) ◽

pp. 93-96 ◽

Cited By ~ 2

Author(s):

Clara Savón ◽

Angel Goyenechea ◽

Angel Valdivia ◽

Danay Chacón ◽

Reynel Cancio ◽

...

Keyword(s):

Monoclonal Antibody ◽

F Protein ◽

Control of Nosocomial Respiratory Syncytial Viral Infections

PEDIATRICS ◽

10.1542/peds.62.5.728 ◽

1978 ◽

Vol 62 (5) ◽

pp. 728-732

Author(s):

Caroline Breese Hall ◽

Joyce M. Geiman ◽

R. Gordon Douglas ◽

Mary Pat Meagher

Keyword(s):

Viral Infections ◽

Close Contact ◽

Initial Infection ◽

Staff Members ◽

Rsv Infection ◽

Syncytial Virus ◽

Repeated Infections

We evaluated methods to control the spread of respiratory syncytial virus (RSV) on our infants' ward during a community outbreak of RSV infection. Methods included isolation and cohorting of infected infants, strict handwashing, use of gowns, and the cohorting of staff to the ill infants. Of 123 infants studied, 36 were admitted with RSV infections. Of the remaining 87 contact infants, eight (19%) acquired nosocomial RSV disease. Three of the eight developed pneumonia and one died. Of the 43 staff members, 24 (56%) became infected and 82% were symptomatic. Four acquired repeated infections within weeks of the initial infection. Studies a year previously had revealed that 45% of contact infants and 42% of the staff had acquired nosocomial RSV infections. Thus, the employed procedures appeared to have decreased the transmission of RSV to infants but not to the staff. Staff may continue to be infected by large droplets from close contact with ill infants or by self-inoculation of contaminated secretions.