Respiratory syncytial virus protein structure, function and implications for subunit vaccine development

2014 ◽  
Vol 9 (8) ◽  
pp. 753-767 ◽  
Author(s):  
Michael McCarthy ◽  
Tonya Villafana ◽  
Elizabeth Stillman ◽  
Mark T Esser
Keyword(s):  
Respiratory Syncytial Virus ◽  
Protein Structure ◽  
Structure Function ◽  
Subunit Vaccine ◽  
Vaccine Development ◽  
Virus Protein ◽  
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 Induction of mucosal immunity and protection by intranasal immunization with a respiratory syncytial virus subunit vaccine formulation

2014 ◽  
Vol 95 (2) ◽  
pp. 301-306 ◽  
Author(s):  
R. Garg ◽  
L. Latimer ◽  
E. Simko ◽  
V. Gerdts ◽  
A. Potter ◽  
...  
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
Lymph Nodes ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Affinity Maturation ◽  
Protein Formulation ◽  
Cross Presentation ◽  
Mucosal Surfaces ◽  
Syncytial Virus

The majority of infections, including those caused by respiratory syncytial virus (RSV), occur at mucosal surfaces. As no RSV vaccine is available our goal is to produce an effective subunit vaccine with an adjuvant suitable for mucosal delivery and cross-presentation. A truncated secreted version of the RSV fusion (ΔF) protein formulated with polyI : C, an innate defence regulator peptide and polyphosphazene, induced local and systemic immunity, including affinity maturation of RSV F-specific IgG, IgA and virus-neutralizing antibodies, and F-specific CD8+ T-cells in the lung, when delivered intranasally. Furthermore, this ΔF protein formulation promoted the production of CD8+ central memory T-cells in the mediastinal lymph nodes and provided protection from RSV challenge. Formulation of ΔF protein with this adjuvant combination enhanced uptake by lung dendritic cells and trafficking to the draining lymph nodes. The ΔF protein formulation was confirmed to be highly efficacious and safe in cotton rats.

scholarly journals Construction and characterization of recombinant vaccinia viruses co-expressing a respiratory syncytial virus protein and a cytokine

2001 ◽  
Vol 82 (9) ◽  
pp. 2107-2116 ◽  
Author(s):  
Teresa R. Johnson ◽  
Julie E. Fischer ◽  
Barney S. Graham
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Antigen Expression ◽  
Virus Protein ◽  
Recombinant Vaccinia ◽  
Vaccinia Viruses ◽  
Ifn Γ ◽  
Syncytial Virus ◽  
The Impact

Recombinant vaccinia viruses are well-characterized tools that can be used to define novel approaches to vaccine formulation and delivery. While vector co-expression of immune mediators has enormous potential for optimizing the composition of vaccine-induced immune responses, the impact on antigen expression and vector antigenicity must also be considered. Co-expression of IL-4 increased vaccinia virus vector titres, while IFN-γ co-expression reduced vaccinia virus replication in BALB/c mice and in C57BL/6 mice infected with some recombinant viruses. Protection against respiratory syncytial virus (RSV) challenge was similar in mice immunized with vaccinia virus expressing RSV G glycoprotein and IFN-γ, even though the replication efficiency of the vector was diminished. These data demonstrate the ability of vector-expressed cytokine to influence the virulence of the vector and to direct the development of selected immune responses. This suggests that the co-expression of cytokines and other immunomodulators has the potential to improve the safety of vaccine vectors while improving the immunogenicity of vaccine antigens.

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 Differential Histopathology and Chemokine Gene Expression in Lung Tissues following Respiratory Syncytial Virus (RSV) Challenge of Formalin-Inactivated RSV- or BBG2Na-Immunized Mice

2001 ◽  
Vol 75 (24) ◽  
pp. 12421-12430 ◽  
Author(s):  
Ultan F. Power ◽  
Thierry Huss ◽  
Vincent Michaud ◽  
Hélène Plotnicky-Gilquin ◽  
Jean-Yves Bonnefoy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Respiratory Syncytial Virus ◽  
Mouse Model ◽  
Subunit Vaccine ◽  
Late Time ◽  
Chemokine Gene ◽  
Time Points ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Chemokine Gene Expression

ABSTRACT A BALB/c mouse model of enhanced pulmonary pathology following vaccination with formalin-inactivated alum-adsorbed respiratory syncytial virus (FI-RSV) and live RSV challenge was used to determine the type and kinetics of histopathologic lesions induced and chemokine gene expression profiles in lung tissues. These data were compared and contrasted with data generated following primary and/or secondary RSV infection or RSV challenge following vaccination with a promising subunit vaccine, BBG2Na. Severe peribronchiolitis and perivascularitis coupled with alveolitis and interstitial inflammation were the hallmarks of lesions in the lungs of FI-RSV-primed mice, with peak histopathology evident on days 5 and 9. In contrast, primary RSV infection resulted in no discernible lesions, while challenge of RSV-primed mice resulted in rare but mild peribronchiolitis and perivascularitis, with no evidence of alveolitis or interstitial inflammation. Importantly, mice vaccinated with a broad dose range (20 to 0.02 μg) of a clinical formulation of BBG2Na in aluminium phosphate demonstrated histopathology similar to that observed in secondary RSV infection. At the molecular level, FI-RSV priming was characterized by a rapid and strong up-regulation of eotaxin and monocyte chemotactic protein 3 (MCP-3) relative gene expression (potent lymphocyte and eosinophil chemoattractants) that was sustained through late time points, early but intermittent up-regulation of GRO/melanoma growth stimulatory activity gene and inducible protein 10 gene expression, while macrophage inflammatory protein 2 (MIP-2) and especially MCP-1 were up-regulated only at late time points. By comparison, primary RSV infection or BBG2Na priming resulted in considerably lower eotaxin and MCP-3 gene expression increases postchallenge, while expression of lymphocyte or monocyte chemoattractant chemokine genes (MIP-1β, MCP-1, and MIP-2) were of higher magnitude and kinetics at early, but not late, time points. Our combined histopathologic and chemokine gene expression data provide a basis for differentiating between aberrant FI-RSV-induced immune responses and normal responses associated with RSV infection in the mouse model. Consequently, our data suggest that BBG2Na may constitute a safe RSV subunit vaccine for use in seronegative infants.

scholarly journals Inferior immunogenicity and efficacy of respiratory syncytial virus fusion protein-based subunit vaccine candidates in aged versus young mice

PLoS ONE ◽  
2017 ◽  
Vol 12 (11) ◽  
pp. e0188708 ◽  
Author(s):  
Corinne Cayatte ◽  
Angie Snell Bennett ◽  
Gaurav Manohar Rajani ◽  
Leigh Hostetler ◽  
Sean K. Maynard ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Fusion Protein ◽  
Subunit Vaccine ◽  
Vaccine Candidates ◽  
Virus Fusion ◽  
Syncytial Virus ◽  
Young Mice
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