Persistently high antibody responses after AS03-adjuvanted H1N1pdm09 vaccine: Dissecting the HA specific antibody response

Anders Madsen,Rebecca J Cox,Åsne Jul-Larsen,Florian Krammer,Mai-Chi Trieu

doi:10.1038/s41541-021-00308-5

Abstract

Current influenza vaccines have a suboptimal effectiveness. The introduction of a novel A/H1N1 influenza virus in 2009 (H1N1pdm09) provided a unique opportunity to study the humoral response to the AS03-adjuvanted H1N1pdm09 vaccine and repeated annual vaccination with the homologous virus in subsequent influenza seasons. Thirty-two HCWs immunized with the AS03-adjuvanted H1N1pdm09 vaccine in 2009 were divided into four groups based on the longevity of their antibody responses (persistently high or transient), and whether they were repeatedly annually vaccinated in the subsequent four influenza seasons or not. Serological assays were utilized to measure the quantity, quality and functionality of antibodies targeting the major surface glycoprotein hemagglutinin (HA). Persistent high responders (hemagglutination inhibition (HI) titre ≥ 80 at 12 months after H1N1pdm09 vaccination) had protective levels of HI antibodies throughout the study period. In addition, the quality and functionality of these antibodies were greater than the individuals who had a transient antibody response to the pandemic vaccine (HI titre < 40 at 12 months after H1N1pdm09 vaccination). All groups had similar levels of antibodies towards the conserved HA stalk domain. The level of HA head-specific antibodies gradually increased over time with annual vaccination in the transient responders. The AS03-adjuvanted H1N1pdm09 vaccine elicited a robust humoral response that persisted up to 5 years in some individuals. Seasonal annual vaccination boosted the HA-antibodies over time in individuals with a transient response to the pandemic H1N1pdm09 vaccine.

Highlights

Influenza is a contagious respiratory pathogen that causes annual epidemics with an estimated 290,000–650,000 deaths each year[1]
While the licensed seasonal inactivated influenza vaccines (IIV) are effective, they lack two essential attributes; firstly the antibody response provide limited potential for crossprotection; and secondly, immunity appears to be of a short of duration[2]
The HA protein consists of a stalk domain and a head domain, the latter being the immunodominant part of the HA protein

Summary

INTRODUCTION

Influenza is a contagious respiratory pathogen that causes annual epidemics with an estimated 290,000–650,000 deaths each year[1]. Vaccination against influenza is the most effective measure to prevent infection and induces B cell responses leading to the production of neutralizing antibodies. HA-head-specific antibodies generated in response to prior infection or immunizations are no longer neutralizing due to the antigenic plasticity of the influenza virus[6]. In Norway, a novel monovalent pandemic vaccine containing the H1N1pdm[09] virus with an oil-in-water emulsion AS03-adjuvant was available in October 2009, just before the peak of the pandemic activity. A 5-year cohort study of HCWs vaccinated with the AS03-adjuvanted. Our initial results from the HCW cohort have shown that the AS03-adjuvanted vaccine provided robust durable antibody responses. The H1N1pdm09-specific antibody titres varied considerably between HCW one year after pandemic vaccination, ranging from protective levels in some individuals to undetectable in others. In order to better understand the longevity of the antibody responses, we dissected the HAspecific antibody response after the AS03-adjuvanted H1N1pdm[09] vaccine with or without annual seasonal vaccination in the subsequent four influenza seasons

RESULTS

DISCUSSION

Findings

METHODS