title: Rabbit hemorrhagic disease virus capsid, a versatile platform for foreign B-cell epitope display inducing protective humoral immune responses.
abstract: Virus-like particles (VLPs), comprised of viral structural proteins devoid of genetic material, are tunable nanoparticles that can be chemically or genetically engineered, to be used as platforms for multimeric display of foreign antigens. Here, we report the engineering of chimeric VLPs, derived from rabbit hemorrhagic disease virus (RHDV) for presentation of foreign B-cell antigens to the immune system. The RHDV capsid comprises 180 copies of a single capsid subunit (VP60). To evaluate the ability of chimeric RHDV VLPs to elicit protective humoral responses against foreign antigens, we tested two B-cell epitopes: a novel neutralizing B-cell epitope, derived from feline calicivirus capsid protein, and a well characterized B-cell epitope from the extracellular domain of influenza A virus M2 protein (M2e). We generated sets of chimeric RHDV VLPs by insertion of the foreign B-cell epitopes at three different locations within VP60 protein (which involved different levels of surface accessibility) and in different copy numbers per site. The immunogenic potential of the chimeric VLPs was analyzed in the mouse model. The results presented here indicated that chimeric RHDV VLPs elicit potent protective humoral responses against displayed foreign B-cell epitopes, demonstrated by both, in vitro neutralization and in vivo protection against a lethal challenge.
authors.affiliation: Centro de Investigación en Sanidad Animal (INIA-CISA), Valdeolmos, 28130 Madrid, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Moreno
authors.affiliation: Centro de Investigación en Sanidad Animal (INIA-CISA), Valdeolmos, 28130 Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Mena
authors.affiliation: Centro de Investigación en Sanidad Animal (INIA-CISA), Valdeolmos, 28130 Madrid, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Angulo
authors.affiliation: Centro de Investigación en Sanidad Animal (INIA-CISA), Valdeolmos, 28130 Madrid, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Gómez
authors.affiliation: Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Crisci
authors.affiliation: Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.|The Pirbright Institute, Ash Road, Woking, Surrey, GU24 0NF, United Kingdom.
authors.forename: María
authors.initials: M
authors.lastname: Montoya
authors.affiliation: Department of Structure of Macromolecules, Centro Nacional de Biotecnología/CSIC, Cantoblanco, 28049 Madrid, Spain.
authors.forename: José R
authors.initials: JR
authors.lastname: Castón
authors.affiliation: Centro de Investigación en Sanidad Animal (INIA-CISA), Valdeolmos, 28130 Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Blanco
authors.affiliation: Centro de Investigación en Sanidad Animal (INIA-CISA), Valdeolmos, 28130 Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Bárcena
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D017929:Hemorrhagic Disease Virus, Rabbit / Q000235:genetics / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology*; D007114:Immunization; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015202:Protein Engineering / Q000379:methods; D011817:Rabbits; D014763:Viral Matrix Proteins / Q000276:immunology; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology; D000086082:Viroporin Proteins
chemical_list: D036022:Capsid Proteins; D018985:Epitopes, B-Lymphocyte; D014763:Viral Matrix Proteins; D015678:Viral Structural Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins