title: The assembly conformation of rotavirus VP6 determines its protective efficacy against rotavirus challenge in mice.
abstract: Viral protein assemblies have shown to be superior immunogens used in commercial vaccines. However, little is known about the effect of protein assembly structure in immunogenicity and the protection conferred by a vaccine. In this work, rotavirus VP6, a polymorphic protein that assembles into nanotubes, icosahedra (dlRLP) or trimers was used to compare the immune response elicited by three different assemblies. VP6 is the most antigenic and abundant rotavirus structural protein. It has been demonstrated that antibodies against VP6 interfere with the replication cycle of rotavirus, making it a vaccine candidate. Groups of mice were immunized with either nanotubes, dlRLP or trimers and the humoral response (IgG and IgA titers) was measured. Immunized mice were challenged with EDIM rotavirus and protection against rotavirus infection, measured as viral shedding, was evaluated. Immunization with nanotubes resulted in the highest IgG titers, followed by immunization with dlRLP. While immunization with one dose of nanotubes was sufficient to reduce viral shedding by 70%, two doses of dlRLP or trimers were required to obtain a similar protection. The results show that the type of assembly of VP6 results in different humoral responses and protection efficacies against challenge with live virus. This information is important for the design of recombinant vaccines in general.
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Ave. Universidad 2001, Cuernavaca, Morelos 62210, Mexico. Electronic address: rpastor@ibt.unam.mx.
authors.forename: Ana Ruth
authors.initials: AR
authors.lastname: Pastor
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Ave. Universidad 2001, Cuernavaca, Morelos 62210, Mexico. Electronic address: william@ibt.unam.mx.
authors.forename: William A
authors.initials: WA
authors.lastname: Rodríguez-Limas
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Ave. Universidad 2001, Cuernavaca, Morelos 62210, Mexico. Electronic address: alicia@ibt.unam.mx.
authors.forename: Martha A
authors.initials: MA
authors.lastname: Contreras
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Ave. Universidad 2001, Cuernavaca, Morelos 62210, Mexico; Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico. Electronic address: neto@ibt.unam.mx.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Esquivel
authors.affiliation: Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico. Electronic address: fernando.esquivel@uaem.mx.
authors.forename: Fernando
authors.initials: F
authors.lastname: Esquivel-Guadarrama
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Ave. Universidad 2001, Cuernavaca, Morelos 62210, Mexico. Electronic address: tonatiuh@ibt.unam.mx.
authors.forename: Octavio T
authors.initials: OT
authors.lastname: Ramírez
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Ave. Universidad 2001, Cuernavaca, Morelos 62210, Mexico. Electronic address: laura@ibt.unam.mx.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Palomares
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D005260:Female; D056724:Immunity, Humoral; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D043942:Nanotubes; D011487:Protein Conformation; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000276:immunology*; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D022243:Rotavirus Vaccines; C061332:VP6 protein, Rotavirus
keywords: Challenge; Protein assembly; Rotavirus; VLP; VP6; Vaccine