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  Evaluation of a novel immunogenic vaccine platform based on a genome replication-deficient Sendai vector

Wiegand, M., Gori-Savellini, G., Martorelli, B., Bossow, S., Neubert, W. J., & Cusi, M. G. (2013). Evaluation of a novel immunogenic vaccine platform based on a genome replication-deficient Sendai vector. VACCINE, 31(37), 3888-3893. doi:10.1016/j.vaccine.2013.06.053.

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Datensatz-Permalink: http://hdl.handle.net/11858/00-001M-0000-0014-78D3-C Versions-Permalink: http://hdl.handle.net/11858/00-001M-0000-0014-78D4-A
Genre: Zeitschriftenartikel

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 Urheber:
Wiegand, Marian1, Autor              
Gori-Savellini, Gianni2, Autor
Martorelli, Barbara2, Autor
Bossow, Sascha3, Autor              
Neubert, Wolfgang J.3, Autor              
Cusi, Maria Grazia2, Autor
Affiliations:
1Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society, escidoc:1565172              
2external, escidoc:persistent22              
3Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society, escidoc:1565145              

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Schlagwörter: RESPIRATORY-SYNCYTIAL-VIRUS; T-CELL RESPONSES; CONFERS PROTECTION; IMMUNE-RESPONSES; RSV INFECTION; F PROTEIN; RECOMBINANT; GENE; TYPE-3; IMMUNOPATHOLOGYReplication-deficient vector; Sendai virus; Vaccine; Respiratory diseases; Mucosal; Immunity;
 Zusammenfassung: 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. (C) 2013 Elsevier Ltd. All rights reserved.

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Sprache(n): eng - Englisch
 Datum: 2013
 Publikationsstatus: Im Druck publiziert
 Seiten: 6
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: ISI: 000324444200020
DOI: 10.1016/j.vaccine.2013.06.053
 Art des Abschluß: -

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Titel: VACCINE
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND : ELSEVIER SCI LTD
Seiten: - Band / Heft: 31 (37) Artikelnummer: - Start- / Endseite: 3888 - 3893 Identifikator: ISSN: 0264-410X