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

• Published in: The Journal of clinical investigation Vol. 125; no. 4; pp. 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: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.04.2015
• 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
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI78450

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.