Palivizumab epitope-displaying virus-like particles protect rodents from RSV challenge

Respiratory syncytial virus (RSV) is the most common cause of serious viral bronchiolitis in infants, young children, and the elderly. Currently, there is not an FDA-approved vaccine available for RSV, though the mAb palivizumab is licensed to reduce the incidence of RSV disease in premature or at-r...

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Bibliographic Details
Published in:The Journal of clinical investigation 2015-04, Vol.125 (4), p.1637-1647
Main Authors: Schickli, Jeanne H, Whitacre, David C, Tang, Roderick S, Kaur, Jasmine, Lawlor, Heather, Peters, Cory J, Jones, Joyce E, Peterson, Darrell L, McCarthy, Michael P, Van Nest, Gary, Milich, David R
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal, Humanized - immunology
Antibodies, Viral - biosynthesis
Antibodies, Viral - immunology
Antibody Specificity
Antigenic determinants
Antigens, Viral - immunology
Binding sites
Biomedical research
Combinatorial Chemistry Techniques
Cryoelectron Microscopy
Enzyme-Linked Immunosorbent Assay
Gene therapy
Health aspects
Helix-Loop-Helix Motifs - immunology
Hepadnavirus
Hepatitis B Virus, Woodchuck - genetics
Humans
Immunodominant Epitopes - immunology
Immunoglobulin G - biosynthesis
Immunoglobulin G - immunology
Innovations
Mice
Mice, Inbred BALB C
Palivizumab
Prevention
Protein Conformation
Proteins
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - immunology
Respiratory syncytial virus
Respiratory Syncytial Virus Infections - prevention & control
Respiratory Syncytial Viruses - immunology
Sigmodontinae
Software
Technical Advance
Vaccination
Vaccines
Vaccines, Virus-Like Particle
Viral Fusion Proteins - chemistry
Viral Fusion Proteins - immunology
Viral Vaccines - immunology
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Summary:Respiratory syncytial virus (RSV) is the most common cause of serious viral bronchiolitis in infants, young children, and the elderly. Currently, there is not an FDA-approved vaccine available for RSV, though the mAb palivizumab is licensed to reduce the incidence of RSV disease in premature or at-risk infants. The palivizumab epitope is a well-characterized, approximately 24-aa helix-loop-helix structure on the RSV fusion (F) protein (F254-277). Here, we genetically inserted this epitope and multiple site variants of this epitope within a versatile woodchuck hepadnavirus core-based virus-like particle (WHcAg-VLP) to generate hybrid VLPs that each bears 240 copies of the RSV epitope in a highly immunogenic arrayed format. A challenge of such an epitope-focused approach is that to be effective, the conformational F254-277 epitope must elicit antibodies that recognize the intact virus. A number of hybrid VLPs containing RSV F254-277 were recognized by palivizumab in vitro and elicited high-titer and protective neutralizing antibody in rodents. Together, the results from this proof-of-principle study suggest that the WHcAg-VLP technology may be an applicable approach to eliciting a response to other structural epitopes.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI78450