scholarly journals Hurdles in Vaccine Development against Respiratory Syncytial Virus

2019 ◽  
Author(s):  
Muhammad Shafique ◽  
Muhammad Asif Zahoor ◽  
Muhammad Imran Arshad ◽  
Bilal Aslam ◽  
Abu Baker Siddique ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Vaccine Development ◽  
Syncytial Virus

scholarly journals Considerations for a Respiratory Syncytial Virus Vaccine Targeting an Elderly Population

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 624
Author(s):  
Laura M. Stephens ◽  
Steven M. Varga
Keyword(s):  
Respiratory Syncytial Virus ◽  
Disease Burden ◽  
Elderly Population ◽  
Vaccine Development ◽  
The Elderly ◽  
The United States ◽  
Susceptible Population ◽  
Age Related ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory syncytial virus (RSV) is most commonly associated with acute lower respiratory tract infections in infants and children. However, RSV also causes a high disease burden in the elderly that is often under recognized. Adults >65 years of age account for an estimated 80,000 RSV-associated hospitalizations and 14,000 deaths in the United States annually. RSV infection in aged individuals can result in more severe disease symptoms including pneumonia and bronchiolitis. Given the large disease burden caused by RSV in the aged, this population remains an important target for vaccine development. Aging results in lowered immune responsiveness characterized by impairments in both innate and adaptive immunity. This immune senescence poses a challenge when developing a vaccine targeting elderly individuals. An RSV vaccine tailored towards an elderly population will need to maximize the immune response elicited in order to overcome age-related defects in the immune system. In this article, we review the hurdles that must be overcome to successfully develop an RSV vaccine for use in the elderly, and discuss the vaccine candidates currently being tested in this highly susceptible population.

scholarly journals Local Evolutionary Patterns of Human Respiratory Syncytial Virus Derived from Whole-Genome Sequencing

2015 ◽  
Vol 89 (7) ◽  
pp. 3444-3454 ◽  
Author(s):  
Charles N. Agoti ◽  
James R. Otieno ◽  
Patrick K. Munywoki ◽  
Alexander G. Mwihuri ◽  
Patricia A. Cane ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Large Scale ◽  
Vaccine Development ◽  
Human Respiratory Syncytial Virus ◽  
Genomic Variation ◽  
Genomic Sequences ◽  
The Novel ◽  
Sequencing Method ◽  
The World ◽  
Syncytial Virus

ABSTRACTHuman respiratory syncytial virus (RSV) is associated with severe childhood respiratory infections. A clear description of local RSV molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. We have generated 27 complete or nearly complete genomes of RSV from hospitalized children attending a rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a novel full-genome deep-sequencing process. Phylogenetic analysis of the new genomes demonstrated the existence and cocirculation of multiple genotypes in both RSV A and B groups in Kilifi. Comparison of local versus global strains demonstrated that most RSV A variants observed locally in Kilifi were also seen in other parts of the world, while the Kilifi RSV B genomes encoded a high degree of variation that was not observed in other parts of the world. The nucleotide substitution rates for the individual open reading frames (ORFs) were highest in the regions encoding the attachment (G) glycoprotein and the NS2 protein. The analysis of RSV full genomes, compared to subgenomic regions, provided more precise estimates of the RSV sequence changes and revealed important patterns of RSV genomic variation and global movement. The novel sequencing method and the new RSV genomic sequences reported here expand our knowledge base for large-scale RSV epidemiological and transmission studies.IMPORTANCEThe new RSV genomic sequences and the novel sequencing method reported here provide important data for understanding RSV transmission and vaccine development. Given the complex interplay between RSV A and RSV B infections, the existence of local RSV B evolution is an important factor in vaccine deployment.

scholarly journals Unravelling the complexities of respiratory syncytial virus RNA synthesis

2006 ◽  
Vol 87 (7) ◽  
pp. 1805-1821 ◽  
Author(s):  
Vanessa M. Cowton ◽  
David R. McGivern ◽  
Rachel Fearns
Keyword(s):  
Respiratory Syncytial Virus ◽  
Vaccine Development ◽  
Virus Genome ◽  
Genome Replication ◽  
Promoter Regions ◽  
Genome Expression ◽  
Virus Rna ◽  
A Genome ◽  
Genome Rnas ◽  
Syncytial Virus

Human respiratory syncytial virus (RSV) is the leading cause of paediatric respiratory disease and is the focus of antiviral- and vaccine-development programmes. These goals have been aided by an understanding of the virus genome architecture and the mechanisms by which it is expressed and replicated. RSV is a member of the order Mononegavirales and, as such, has a genome consisting of a single strand of negative-sense RNA. At first glance, transcription and genome replication appear straightforward, requiring self-contained promoter regions at the 3′ ends of the genome and antigenome RNAs, short cis-acting elements flanking each of the genes and one polymerase. However, from these minimal elements, the virus is able to generate an array of capped, methylated and polyadenylated mRNAs and encapsidated antigenome and genome RNAs, all in the appropriate ratios to facilitate virus replication. The apparent simplicity of genome expression and replication is a consequence of considerable complexity in the polymerase structure and its cognate cis-acting sequences; here, our understanding of mechanisms by which the RSV polymerase proteins interact with signals in the RNA template to produce different RNA products is reviewed.

scholarly journals Meeting report: WHO consultation on Respiratory Syncytial Virus (RSV) vaccine development, Geneva, 25–26 April 2016

Vaccine ◽  
2019 ◽  
Vol 37 (50) ◽  
pp. 7355-7362 ◽  
Author(s):  
Birgitte K. Giersing ◽  
Ruth A. Karron ◽  
Johan Vekemans ◽  
David C. Kaslow ◽  
Vasee S. Moorthy
Keyword(s):  
Respiratory Syncytial Virus ◽  
Vaccine Development ◽  
Meeting Report ◽  
Syncytial Virus

scholarly journals Neutralization of Human Respiratory Syncytial Virus Infectivity by Antibodies and Low-Molecular-Weight Compounds Targeted against the Fusion Glycoprotein

2010 ◽  
Vol 84 (16) ◽  
pp. 7970-7982 ◽  
Author(s):  
Margarita Magro ◽  
David Andreu ◽  
Paulino Gómez-Puertas ◽  
José A. Melero ◽  
Concepción Palomo
Keyword(s):  
Molecular Weight ◽  
Respiratory Syncytial Virus ◽  
Vaccine Development ◽  
Human Respiratory Syncytial Virus ◽  
Heptad Repeat ◽  
Low Molecular Weight ◽  
Virus Infectivity ◽  
F Protein ◽  
Low Molecular Weight Compounds ◽  
Syncytial Virus

ABSTRACT Human respiratory syncytial virus (HRSV) fusion (F) protein is an essential component of the virus envelope that mediates fusion of the viral and cell membranes, and, therefore, it is an attractive target for drug and vaccine development. Our aim was to analyze the neutralizing mechanism of anti-F antibodies in comparison with other low-molecular-weight compounds targeted against the F molecule. It was found that neutralization by anti-F antibodies is related to epitope specificity. Thus, neutralizing and nonneutralizing antibodies could bind equally well to virions and remained bound after ultracentrifugation of the virus, but only the former inhibited virus infectivity. Neutralization by antibodies correlated with inhibition of cell-cell fusion in a syncytium formation assay, but not with inhibition of virus binding to cells. In contrast, a peptide (residues 478 to 516 of F protein [F478-516]) derived from the F protein heptad repeat B (HRB) or the organic compound BMS-433771 did not interfere with virus infectivity if incubated with virus before ultracentrifugation or during adsorption of virus to cells at 4°C. These inhibitors must be present during virus entry to effect HRSV neutralization. These results are best interpreted by asserting that neutralizing antibodies bind to the F protein in virions interfering with its activation for fusion. Binding of nonneutralizing antibodies is not enough to block this step. In contrast, the peptide F478-516 or BMS-433771 must bind to F protein intermediates generated during virus-cell membrane fusion, blocking further development of this process.

scholarly journals Single Immunization of a Vaccine Vectored by a Novel Recombinant Vaccinia Virus Affords Effective Protection Against Respiratory Syncytial Virus Infection in Cotton Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Marsha S. Russell ◽  
Sathya N. Thulasi Raman ◽  
Caroline Gravel ◽  
Wanyue Zhang ◽  
Annabelle Pfeifle ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Vaccinia Virus ◽  
High Efficiency ◽  
Vaccine Development ◽  
Nasal Administration ◽  
Effective Vaccine ◽  
High Dose ◽  
Cotton Rats ◽  
Syncytial Virus ◽  
Vectored Vaccine

Respiratory syncytial virus (RSV) is a leading cause of respiratory infections worldwide and disease management measures are hampered by the lack of a safe and effective vaccine against the infection. We constructed a novel recombinant RSV vaccine candidate based on a deletion mutant vaccinia virus platform, in that the host range genes E3L and K3L were deleted (designated as VACVΔE3LΔK3L) and a poxvirus K3L ortholog gene was used as a marker for the rapid and efficient selection of recombinant viruses. The safety of the modified vaccinia virus was investigated by intranasal administration of BALB/c mice with the modified vaccinia vector using a dose known to be lethal in the wild-type Western Reserve. Only a minor loss of body weight by less than 5% and mild pulmonary inflammation were observed, both of which were transient in nature following nasal administration of the high-dose modified vaccinia virus. In addition, the viruses were cleared from the lung in 2 days with no viral invasions of the brain and other vital organs. These results suggest that the virulence of the virus has been essentially abolished. We then investigated the efficiency of the vector for the delivery of vaccines against RSV through comparison with another RSV vaccine delivered by the widely used Modified Vaccinia virus Ankara (MVA) backbone. In the cotton rats, we found a single intramuscular administration of VACVΔE3LΔK3L-vectored vaccine elicited immune responses and protection at a level comparable to the MVA-vectored vaccine against RSV infection. The distinct features of this novel VACV vector, such as an E3L deletion for attenuation and a K3L ortholog for positive selection and high efficiency for vaccine delivery, could provide unique advantages to the application of VACV as a platform for vaccine development.

scholarly journals 92. Incidence of Respiratory Syncytial Virus Infection among Hospitalized Adults, 2017–2019

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S7-S8
Author(s):  
Angela Branche ◽  
Lisa Saiman ◽  
Edward E Walsh ◽  
Ann R Falsey ◽  
William Sieling ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Census Data ◽  
Vaccine Development ◽  
Respiratory Illness ◽  
Incidence Rates ◽  
Case Definition ◽  
Cardiopulmonary Disease ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Surveillance Area

Abstract Background Respiratory syncytial virus (RSV) infection has been increasingly recognized as an important cause of acute respiratory illness (ARI) and a trigger for exacerbation of underlying cardiopulmonary disease in adults. Incidence of hospitalized RSV infection remains uncertain as adults have not been systematically screened. Previous incidence estimates, derived primarily from modeling studies, have ranged from 84 to 190/100K population in adults >65 years of age. Accurate burden data are critical to inform RSV vaccine development for adults. We used active surveillance among hospitalized adults to determine population-based incidence rates of RSV infection. Methods Hospitalized adults ≥ 18 years old residing in the surveillance area with >2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened for eligibility during October 2017–April 2018 and October 2018 to April 2019 in 3 hospitals in Rochester, NY and New York City. Respiratory specimens were tested for RSV using PCR assays. RSV incidence per 100,000 persons (per 2010 US Census data) was adjusted by percent market share for study hospitals in their catchment area. Results In total, 8,217 hospitalized adults residing in the surveillance area that met the surveillance case definition were tested for RSV; 768 (9.4%) were positive. Adults were aged 18–49 (12%), 50–64 (30%), and ≥65 years old (58%); 55% were female. RSV infection incidence varied from year 1 to year 2 and was highest in patients aged ≥65 years old (table). Conclusion This is the largest prospective RSV incidence study to date. Preliminary results indicate that the incidence of RSV infection may be higher than previously reported, especially in urban-dwelling adults >65 years of age. Results confirm the need for vaccines to prevent RSV infections in older adults. Disclosures All Authors: No reported Disclosures.

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