ISCOMATRIX™ adjuvant promotes epitope spreading and antibody affinity maturation of influenza A H7N9 virus like particle vaccine that correlate with virus neutralization in humans

•H7N9 VLP vaccine with ISCOMATRIX™ adjuvant showed enhanced neutralizing antibody responses in humans.•Unadjuvanted H7N9-VLP vaccine generated primarily antibodies targeting the C-terminus of the globular HA1 domain.•Adjuvanted H7N9-VLP vaccine generated antibodies against large conformational epitopes in the HA1 spanning the receptor binding domain (RBD).•Adjuvanted H7N9-VLP promotes better antibody affinity maturation to HA1 than unadjuvanted vaccine that correlates with Virus neutralization.•This study shows that ISCOMATRIX™ adjuvanted vaccine promotes higher quality antibody immune response against avian influenza in humans.