Impaired Vaccine-Induced Antibody Response Against Clade 6B H1N1 Viruses in Individuals Before Viral Emergence

Open Forum Infect Dis. 2020 Jan 11;7(1):ofz513. doi: 10.1093/ofid/ofz513. eCollection 2020 Jan.

Abstract

Background: Clade 6B H1N1 pdm09 influenza viruses cause substantial morbidity and mortality worldwide. Human antibody profiles elicited upon vaccination against the clade 6B virus are largely unclear before viral emergence.

Methods: Healthy volunteers, including children aged 3-8 years, adolescents aged 9-17 years, and adults, were enrolled before the clade 6B H1N1 outbreak and received the 2013-2014 inactivated influenza vaccine. We determined antibody responses before and after vaccination. Vaccine-induced plasmablast-derived antibodies were tested against H1N1 pdm09 reference and clade 6B viruses.

Results: The majority of the subjects generated robust hemagglutination inhibition and neutralizing antibody responses upon vaccination across the different age groups. Nevertheless, a subset of young adults preferentially produced antibodies that failed to neutralize clade 6B viruses that emerged and circulated in 2014-2016. The hemagglutinin K163Q change at the Sa antigenic site, one of the substitutions that define clade 6B viruses, was responsible for resistance to neutralization by both postvaccination sera and vaccine-induced plasmablast-derived antibodies.

Conclusions: Vaccine-induced antibody immunity is compromised by the antigenic change of H1N1 pdm09 virus in a subset of adults, and this may warrant the incorporation of human serology in the antigenic characterization of virus and vaccine strain selection.

Keywords: antigenic drift; clade 6B H1N1 pdm09 virus; human serum; inactivated influenza vaccine; plasmablast-derived polyclonal antibodies.