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.
Highlights
Over 400 human cases of infections with highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype have been reported since 2003
The minimal requirements were assessed for the induction of protective immunity in mice against antigenically distinct influenza A/H5N1 viruses with a recombinant modified vaccinia virus Ankara (MVA) expressing the HA gene of a clade 1 influenza A/ H5N1virus
Two immunizations with a dose as low as 104 pfu of MVA-HA-virus neutralization (VN)/04 were sufficient for the induction of protective immunity against the homologous strain and against the antigenically distinct strain A/IND/5/05 from clade 2.1
Summary
Over 400 human cases of infections with highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype have been reported since 2003. More than 60% of these cases had a fatal outcome and new cases continue to be reported frequently[1]. Once these viruses become transmittable from human-to-human by adaption to their new host, a new influenza pandemic is imminent. Neutralizing antibodies against H5N1 viruses are virtually absent in the human population and already nine different clades of antigenically distinct viruses have been identified [2]. The use of adjuvants can increase the immunogenicity of seasonal and pandemic influenza vaccines and may lower the amount of antigen needed for the induction of protective antibody responses [15,16,17,18,19]
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