Abstract
BackgroundNew highly pathogenic H5N1 influenza viruses are continuing to evolve with a potential threat for an influenza pandemic. So far, the H5N1 influenza viruses have not widely circulated in humans and therefore constitute a high risk for the non immune population. The aim of this study was to evaluate the cross-protective potential of the hemagglutinins of five H5N1 strains of divergent clades using a live attenuated modified vaccinia Ankara (MVA) vector vaccine.Methodology/Principal FindingsThe replication-deficient MVA virus was used to express influenza hemagglutinin (HA) proteins. Specifically, recombinant MVA viruses expressing the HA genes of the clade 1 virus A/Vietnam/1203/2004 (VN/1203), the clade 2.1.3 virus A/Indonesia/5/2005 (IN5/05), the clade 2.2 viruses A/turkey/Turkey/1/2005 (TT01/05) and A/chicken/Egypt/3/2006 (CE/06), and the clade 2.3.4 virus A/Anhui/1/2005 (AH1/05) were constructed. These experimental live vaccines were assessed in a lethal mouse model. Mice vaccinated with the VN/1203 hemagglutinin-expressing MVA induced excellent protection against all the above mentioned clades. Also mice vaccinated with the IN5/05 HA expressing MVA induced substantial protection against homologous and heterologous AH1/05 challenge. After vaccination with the CE/06 HA expressing MVA, mice were fully protected against clade 2.2 challenge and partially protected against challenge of other clades. Mice vaccinated with AH1/05 HA expressing MVA vectors were only partially protected against homologous and heterologous challenge. The live vaccines induced substantial amounts of neutralizing antibodies, mainly directed against the homologous challenge virus, and high levels of HA-specific IFN-γ secreting CD4 and CD8 T-cells against epitopes conserved among the H5 clades and subclades.Conclusions/SignificanceThe highest level of cross-protection was induced by the HA derived from the VN/1203 strain, suggesting that pandemic H5 vaccines utilizing MVA vector technology, should be based on the VN/1203 hemagglutinin. Furthermore, the recombinant MVA-HA-VN, as characterized in the present study, would be a promising candidate for such a vaccine.
Highlights
Influenza A viruses infect, among other hosts, aquatic birds, poultry, swine and humans [1]
According to the standard nomenclature system based upon the evolution of the H5 hemagglutinin genes, the H5N1 influenza viruses are grouped in different clades [25]
For a direct comparison of the cross protective capacity of HA antigens from different clades, the HA genes were engineered into otherwise identical recombinant modified vaccinia Ankara (MVA) vectors that were used for immunization experiments
Summary
Influenza A viruses infect, among other hosts, aquatic birds, poultry, swine and humans [1]. The highly pathogenic avian influenza (HPAI) viruses are considered candidates for a new pandemic. The H5N1 influenza subtype has not circulated in the human population. Since the exact subtype and clade of a potential future pandemic strain is not known, broad crossprotection is a highly desirable feature of any pre-pandemic vaccine. New highly pathogenic H5N1 influenza viruses are continuing to evolve with a potential threat for an influenza pandemic. The H5N1 influenza viruses have not widely circulated in humans and constitute a high risk for the non immune population. The aim of this study was to evaluate the cross-protective potential of the hemagglutinins of five H5N1 strains of divergent clades using a live attenuated modified vaccinia Ankara (MVA) vector vaccine
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