Preclinical evaluation of influenza vaccines based on replication-deficient poxvirus vector MVA

Abstract

The zoonotic transmissions of highly pathogenic avian influenza viruses of the H5N1 subtype hat occur since 1997 have sparked the development of novel influenza vaccines. The advent of reverse genetics technology, cell culture production techniques and novel adjuvants has improved the vaccine strain preparation, the production process and the immunogenicity of the vaccines respectively and would accelerated the availability of pandemic influenza vaccines. However, there is still room for improvement and alternative vaccine preparations are explored such as recombinant antigens (e.g. baculovirus expression) and viral vectors. Modified Vaccinia virus Ankara (MVA), originally developed as a safe smallpox vaccine can be exploited as a viral vector. It has favourable properties, which makes it an attractive candidate as a pandemic influenza vaccine (for review see reference [1]). Recently we have evaluated a MVA-based vaccine for highly pathogenic influenza virus of the H5N1 subtype in mice and macaques. To this end, recombinant MVA was constructed expressing the gene encoding the hemagglutinin of H5N1 influenza virus A/Vietnam/1194/04 (clade 1) (MVA-HA-VN/04) and used to immunize C57BL/6 mice and cynomolgus macaques (macaca fascicularis). Two immunizations induced strong virus specific antibody responses in both species and protected the animals from the development of severe disease observed in control animals inoculated with empty MVA vector or PBS after challenge infection with the homologous or the antigenically distinct influenza virus A/Indonesia/5/05 (clade 2.1). In vaccinated animals virus replication in the respiratory tract was not detectable and the development of histopathological changes in the lungs was prevented. Furthermore, a MVA-based 2009 pandemic H1N1 vaccine protected against severe disease in a pH1N1 ferret model. The preclinical evaluation of MVA-based candidate vaccines indicated that they have potential as vaccines against highly pathogenic H5N1 and pH1N1 influenza viruses. The MVA-based vaccines proved to be immunogenic and induced broad-protective immune responses. MVA has favourable properties for the production, storage and use as a pandemic influenza vaccine and further clinical development seems warranted.