No evidence of antigenic seniority in hemagglutinin specific antibody responses after adjuvanted pandemic 2009 influenza vaccination

Anders Madsen,Linda Azimi,Sarah Tete,Fan Zhou,Florian Krammer,Rebecca Jane Cox,Åsne Jul-Larsen

doi:10.1016/j.jvacx.2019.100029

Anders Madsen, Linda Azimi + Show 5 more

Open Access

https://doi.org/10.1016/j.jvacx.2019.100029

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Abstract

Influenza is a contagious respiratory illness caused by the influenza virus. The pandemic outbreak of influenza A H1N1 in 2009 (H1N1pdm09) gave us a unique opportunity to study humoral immune responses to a novel influenza vaccine strain. Here, we investigate how an individual’s previous encounter with different influenza subtypes influences the humoral response after pandemic vaccination in 2009.We retrospectively chose and grouped 80 vaccinated healthcare workers (HCWs) based on their year of birth into 4 groups, reflecting which influenza subtype they were likely first exposed to during childhood. Pre- and 21 days post- vaccination sera were analyzed. We investigated antibodies to the major surface protein hemagglutinin (HA), and specifically antibodies binding to the conserved stalk domain of the HA-protein. Serological assays were used to assess the quantity and functionality of the influenza-specific antibodies, including virus neutralization and activation of natural killer (NK) cells involved in antibody-dependent cell-mediated cytotoxicity (ADCC).The AS03-adjuvanted H1N1pdm09 vaccine elicited robust antibody responses in all groups of HCWs. We found that the more antigenically experienced individuals had higher pre-vaccination antibody-levels towards the stalk domain of the HA. We also demonstrated that despite their inferior pre-vaccination antibody levels, the younger individuals reached similar antibody levels as the older birth-cohorts after pandemic vaccination. Our findings are important for understanding the effect of AS03 adjuvant on the antibody response in individuals exposed to different influenza viruses during their early childhood years, which is crucial for developing vaccine strategies against influenza.

Highlights

Influenza is a contagious respiratory disease causing annual epidemics with an estimated 300,000–600,000 deaths each year [1]
We have investigated how priming to different circulating influenza subtypes during childhood influences the immune response to adjuvanted pandemic H1N1 vaccination in healthcare workers (HCW)
HCWs are an important risk group with high occupational exposure to influenza that were prioritised for the first rounds of vaccination against pandemic influenza [24]

Summary

Introduction

Influenza is a contagious respiratory disease causing annual epidemics with an estimated 300,000–600,000 deaths each year [1]. Morbidity and mortality can increase dramatically when, at an unpredictable interval, a pandemic occurs. In April 2009 a novel influenza A H1N1 virus emerged (H1N1pdm09), with high transmissibility among humans. The virus spread globally, and a pandemic was declared on June 11th 2009 [2]. Vaccination against influenza can reduce infection, disease severity and death, and. In 2009, Norway initiated a mass vaccination campaign to protect the population. Around 2.2 million people were vaccinated with the AS03 adjuvanted monovalent pandemic influenza vaccine during the pandemic, and healthcare workers (HCW) were prioritised for receiving the first round of vaccination before the peak of pandemic virus activity [3]

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