title: MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization.
abstract: Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, result in high morbidity and mortality. It is feared that these viruses become pandemic, therefore the development of safe and effective vaccines is desirable. MVA-based H5N1 vaccines already proved to be effective when two immunizations with high doses were used. Dose-sparing strategies would increase the number of people that can be vaccinated when the amount of vaccine preparations that can be produced is limited. Furthermore, protective immunity is induced ideally after a single immunization. Therefore the minimal requirements for induction of protective immunity with a MVA-based H5N1 vaccine were assessed in mice. To this end, mice were vaccinated once or twice with descending doses of a recombinant MVA expressing the HA gene of influenza virus A/Vietnam/1194/04. The protective efficacy was determined after challenge infection with the homologous clade 1 virus and a heterologous virus derived from clade 2.1, A/Indonesia/5/05 by assessing weight loss, virus replication and histopathological changes. It was concluded that MVA-based vaccines allowed significant dose-sparing and afford cross-clade protection, also after a single immunization, which are favorable properties for an H5N1 vaccine candidate.
authors.affiliation: Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Joost H C M
authors.initials: JH
authors.lastname: Kreijtz
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Suezer
authors.forename: Gerrie
authors.initials: G
authors.lastname: de Mutsert
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.forename: Astrid
authors.initials: A
authors.lastname: Schwantes
authors.forename: Judith M A
authors.initials: JM
authors.lastname: van den Brand
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.forename: Johannes
authors.initials: J
authors.lastname: Löwer
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Gerd
authors.initials: G
authors.lastname: Sutter
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
mesh_terms: D000818:Animals; D004285:Dogs; D005260:Female; D006801:Humans; D007114:Immunization; D007150:Immunohistochemistry / Q000379:methods; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics*; D007252:Influenza Vaccines / Q000235:genetics*; D007251:Influenza, Human / Q000517:prevention & control; D008168:Lung / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D011994:Recombinant Proteins / Q000737:chemistry; D014612:Vaccines / Q000737:chemistry
chemical_list: D007252:Influenza Vaccines; D011994:Recombinant Proteins; D014612:Vaccines