Background:

Highly pathogenic avian influenza viruses continue to circulate in poultry and wild birds and occasionally infect humans, sometimes with fatal outcome. Development of vaccines is a priority to prepare for potential pandemics, however complicated by antigenic variation of the surface glycoprotein hemagglutinin. We report the immunological profile induced by human immunization with Modified Vaccinia virus Ankara expressing the hemagglutinin gene of H5N1 virus A/Vietnam/1194/04 (rMVA-H5).

Methods:

In a double-blind phase 1/2a clinical trial, 79 individuals received one or two injections of rMVA-H5 or vector control. Twenty-seven study subjects received a booster immunization after one year. The breadth, magnitude, and properties of vaccine-induced antibody and T-cell responses were characterised.

Results:

rMVA-H5 induced broadly-reactive antibody responses, demonstrated by protein microarray, hemagglutination inhibition, virus neutralization and antibody-dependent cellular cytotoxicity assays. Antibodies cross-reacted with antigenically distinct H5 viruses, including the recently emerged H5N6 and H5N8, and currently circulating H5N1 viruses. In addition, the induction of T-cells specific for H5 viruses of two different clades was demonstrated.

Conclusions:

rMVA-H5 induced immune responses that cross-reacted with H5 viruses of various clades. These findings validate rMVA-H5 as vaccine candidate against antigenically distinct H5 viruses. This trial is registered with the Dutch Trial Register, number NTR3401