title: Evaluation of a novel immunogenic vaccine platform based on a genome replication-deficient Sendai vector.
abstract: We developed a novel vaccine platform based on a paramyxoviral, genome replication-deficient Sendai virus vector that can express heterologous genes inserted into the genome. To validate the novel approach in vivo, we generated a combined vaccine candidate against human respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (PIV3). The present study compares two different methods of displaying heterologous antigens: (i) the RSV fusion (F) protein, encoded as a secretable version in an additional transcription unit, serves as an antigen only after being expressed in infected cells; (ii) PIV3 fusion (F) and hemagglutinin-neuraminidase (HN) genes, replacing Sendai counterparts in the vector genome, are also expressed as structural components on the surface of vaccine particles. The efficacy of this prototype vaccine was assessed in a mouse model after mucosal administration. The vaccine candidate was able to elicit specific mucosal, humoral and T cell-mediated immune responses against RSV and PIV3. However, PIV3 antigen display on the vaccine particles' surface induced higher antibody titers than the RSV antigen, being expressed only after cell infection. Consequently, this construct induced an adequate neutralizing antibody response only to PIV3. Finally, replicating virus particles were not detected in the lungs of immunized mice, confirming the genome stability and replication deficiency of this vaccine vector in vivo. Both factors can contribute substantially to the safety profile of vaccine candidates. In conclusion, this replication-deficient Sendai vector represents an efficient platform that can be used for vaccine developments against various viral pathogens.
authors.affiliation: Department of Molecular Virology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany. wiegand@amvac-research.de
authors.forename: Marian
authors.initials: M
authors.lastname: Wiegand
authors.forename: Gianni
authors.initials: G
authors.lastname: Gori-Savellini
authors.forename: Barbara
authors.initials: B
authors.lastname: Martorelli
authors.forename: Sascha
authors.initials: S
authors.lastname: Bossow
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Neubert
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cusi
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D005260:Female; D005822:Genetic Vectors; D016679:Genome, Viral; D015707:HN Protein / Q000235:genetics; D056724:Immunity, Humoral; D051379:Mice; D008807:Mice, Inbred BALB C; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D022261:Respiratory Syncytial Virus Vaccines / Q000235:genetics / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000472:pathogenicity; D029082:Sendai virus / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics* / Q000276:immunology* / Q000494:pharmacology; D014760:Viral Fusion Proteins / Q000235:genetics; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; C526850:F protein, human respiratory syncytial virus; D015707:HN Protein; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D014760:Viral Fusion Proteins
keywords: Immunity; Mucosal; Replication-deficient vector; Respiratory diseases; Sendai virus; Vaccine