title: Rotavirus capsid VP6 protein acts as an adjuvant in vivo for norovirus virus-like particles in a combination vaccine.
abstract: Rotavirus (RV) and norovirus (NoV) are the 2 leading causes of acute viral gastroenteritis worldwide. We have developed a non-live NoV and RV vaccine candidate consisting of NoV virus-like particles (VLPs) and recombinant polymeric RV VP6 protein produced in baculovirus-insect cell expression system. Both components have been shown to induce strong potentially protective immune responses. As VP6 nanotubes are highly immunogenic, we investigated here a possible adjuvant effect of these structures on NoV-specific immune responses in vivo. BALB/c mice were immunized intramuscularly with a suboptimal dose (0.3 μg) of GII.4 or GI.3 VLPs either alone or in a combination with 10 μg dose of VP6 and induction of NoV-specific antibodies in sera of experimental animals were measured. Blocking assay using human saliva or synthetic histo-blood group antigens was employed to test NoV blocking antibodies. Suboptimal doses of the VLPs alone did not induce substantial anti-NoV antibodies. When co-administered with the VP6, considerable titers of not only type-specific but also cross-reactive IgG antibodies against NoV VLP genotypes not included in the vaccine composition were induced. Most importantly, NoV-specific blocking antibodies, a surrogate for neutralizing antibodies, were generated. Our results show that RV VP6 protein has an in vivo adjuvant effect on NoV-specific antibody responses and support the use of VP6 protein as a part of the NoV-RV combination vaccine, especially when addition of external adjuvants is not desirable.
authors.affiliation: a Vaccine Research Center, University of Tampere Medical School , Tampere , Finland.
authors.forename: Vesna
authors.initials: V
authors.lastname: Blazevic
authors.affiliation: a Vaccine Research Center, University of Tampere Medical School , Tampere , Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Malm
authors.affiliation: b R&D Project Office, UMN Pharma Inc. , Yokohama , Kanagawa , Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Arinobu
authors.affiliation: a Vaccine Research Center, University of Tampere Medical School , Tampere , Finland.
authors.forename: Suvi
authors.initials: S
authors.lastname: Lappalainen
authors.affiliation: a Vaccine Research Center, University of Tampere Medical School , Tampere , Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Vesikari
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000008:administration & dosage / Q000378:metabolism*; D016367:Baculoviridae / Q000235:genetics; D036022:Capsid Proteins / Q000008:administration & dosage / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D005822:Genetic Vectors; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007313:Insecta; D008807:Mice, Inbred BALB C; D017778:Vaccines, Combined; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D007074:Immunoglobulin G; C061332:VP6 protein, Rotavirus; D017778:Vaccines, Combined; D058425:Vaccines, Virus-Like Particle; D014765:Viral Vaccines
keywords: VLP; VP6; adjuvant; blocking antibodies; norovirus; rotavirus; vaccine