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

The Journal of Clinical Investigation
Jeanne H SchickliDavid R Milich

Abstract

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.

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Citations

Oct 28, 2015·Expert Review of Vaccines·Noushin JaberolansarMariusz Skwarczynski
Aug 8, 2015·Vaccine·Fernando P Polack
Apr 9, 2016·Human Vaccines & Immunotherapeutics·Jon Oscherwitz
Jun 27, 2015·Antiviral Research·Timothy M BlockCarol L Brosgart
Jun 14, 2016·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Hirokazu KimuraAkihide Ryo
Jun 28, 2016·Current Opinion in Immunology·Antonio LanzavecchiaDavide Corti
Aug 25, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Pierre-Louis HervéSabine Riffault
May 18, 2018·Antiviral Chemistry & Chemotherapy·M S BoukhvalovaJcg Blanco
Dec 18, 2015·Clinical and Vaccine Immunology : CVI·Patricio L AcostaFernando P Polack
Dec 7, 2019·Human Vaccines & Immunotherapeutics·D C WhitacreD R Milich
May 14, 2020·Viruses·Allison E Norlander, R Stokes Peebles
Feb 13, 2021·Scientific Reports·Kristina BorochovaRudolf Valenta
Dec 22, 2020·Future Virology·Laura M Stephens, Steven M Varga
Apr 27, 2021·Monoclonal Antibodies in Immunodiagnosis and Immunotherapy·Deepak KumarNagendra R Hegde
Jun 10, 2016·Clinical Microbiology Reviews·Erik De Clercq, Guangdi Li

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Methods Mentioned

BETA
ELISA
gel filtration

Software Mentioned

Prism Graphpad
Excel

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