Impact of pre-existing immunity on the induction of functional cross-reactive anti-hemagglutinin stalk antibodies following vaccination with an AS03 adjuvanted pandemic H1N1 vaccine

Abstract The 2009 pandemicH1N1 (A(H1N1)pdm09) virus had a highly divergent hemagglutinin(HA) compared to pre-2009 seasonal H1N1 strains. Most peoples were immunologically naive to the A(H1N1)pdm09, although hospital workers were exposed early in the pandemicbefore pandemicvaccines became available. Here, we evaluated how pre-existingantibodies influence the induction of cross-functional HA stalkantibodies following A(H1N1)pdm09 vaccination. Fifty-six healthcare workers vaccinated with AS03adjuvanted A(H1N1)pdm09 vaccine were chosen by their pre-vaccination priming status (primed HI titers ≥ 40 or unprimed  Primed individuals had higher pre-existingHA head- and stalk-specific IgG1, as well as higher ADCC functionality of stalkantibodies. However, following vaccination with the adjuvanted pandemicvaccine, only the quantity of HA head specific IgG1 antibodies were significantly higher than in unprimed individuals. The priming status did not impact upon the cross-reactive HA stalkspecific IgG antibodies or their ability to neutralize virus or induce ADCC post-vaccination. In conclusion, a single dose of AS03adjuvanted pandemicvaccine elicited similar levels of functional antibodies in naive and primed individuals. These findings are important for understanding the immunological factors that impact or modulate pandemicvaccine responses in humans.