München, Germany
München, Germany

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Zuniga A.,ZHAW Zurich University of Applied Sciences | Liniger M.,Institute of Virology and Immunoprophylaxis | Morin T.N.A.,Vifor Ltd | Marty R.R.,Spirig Pharma AG | And 5 more authors.
Human Vaccines and Immunotherapeutics | Year: 2013

The measles virus vaccine (MVbv) is a clinically certified and well-tolerated vaccine strain that has been given both parenterally and mucosally. It has been extensively used in children and has proven to be safe and effective in eliciting protective immunity. This specific strain was therefore chosen to generate a measles viral vector. The genome of the commercial MVbv vaccine strain was isolated, sequenced and a plasmid, p(+)MVb, enabling transcription of the viral antigenome and rescue of MVb, was constructed. Phylogenic and phenotypic analysis revealed that MVbv and the rescued MVb constitute another evolutionary branch within the hitherto classified measles vaccines. Plasmid p(+)MVb was modified by insertion of artificial MV-type transcription units (ATUs) for the generation of recombinant viruses (rMVb) expressing additional proteins. Replication characteristics and immunogenicity of rMVb vectors were similar to the parental MVbv and to other vaccine strains. The expression of the additional proteins was stable over 10 serial virus transfers, which corresponds to an amplification greater than 1020. The excellent safety record and its efficient application as aerosol may add to the usefulness of the derived vectors. © 2013 Landes Bioscience.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.0-1;HEALTH.2013.1.3-4 | Award Amount: 7.80M | Year: 2013

Although vaccination is the cornerstone of prophylaxis, current vaccines provide only moderate protection. Most employ inactivated or protein-based, including multimeric antigen, vaccines requiring annual updating. Their limited antigen loads provide limited capacity for inducing robust immune defences, without assurance that both humoral and cell mediated (CMI) responses, as well as durable immunity, will be induced. Replicating vaccines may provide several rounds of antigen production, increasing potential for humoral and CMI defence induction. Neither live, attenuated nor vector vaccines can be produced synthetically, being reliant on cell culture or egg production. They cannot be targeted to immune cells; interference from pre-existing immunity is also a risk. Efficacious, synthetic vaccines would be the answer, as seen with self-replicating RNA replicon (RepRNA) technology these replicate and translate without producing infectious progeny. RepRNA produced in vitro is combined with synthetic delivery vehicles targeting dendritic cell (DC) receptors essential for efficient immune defences with glycoconjugate ligands. The UniVax project promotes the first synergising of approaches with synthetic targeted delivery systems for RepRNA. The innovation integrates technologies of (i) RepRNA vaccines, (ii) lipoplexes (biodegradable lipid/adjuvant/RNA for cytosolic delivery), (iii) polyplexes (biodegradable, polysaccharide vehicles), (iv) glycoconjugates targeting DC receptors, (v) adjuvants with well-defined molecular targets and effector functions. This promotes efficacious mucosal and systemic responses, ensuring for the first time both humoral and CMI responses. Components developed in PANFLUVAC and Replixcel projects allow UniVax to create the first Universal Flu vaccine prototypes. This innovative approach creates the first synthetic vaccine of its kind, promoting consortium SMEs to a unique position of world leaders.

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