Repeat vaccination reduces antibody affinity maturation across different influenza vaccine platforms in humans

Surender Khurana,Megan Hahn,Lisa R King,Andrea Sant,Elizabeth M Coyle,John Treanor,Tsai-Lien Lin,Hana Golding

doi:10.1038/s41467-019-11296-5

Surender Khurana, Megan Hahn + Show 6 more

Open Access

https://doi.org/10.1038/s41467-019-11296-5

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Abstract

Several vaccines are approved in the United States for seasonal influenza vaccination every year. Here we compare the impact of repeat influenza vaccination on hemagglutination inhibition (HI) titers, antibody binding and affinity maturation to individual hemagglutinin (HA) domains, HA1 and HA2, across vaccine platforms. Fold change in HI and antibody binding to HA1 trends higher for H1N1pdm09 and H3N2 but not against B strains in groups vaccinated with FluBlok compared with FluCelvax and Fluzone. Antibody-affinity maturation occurs against HA1 domain of H1N1pdm09, H3N2 and B following vaccination with all vaccine platforms, but not against H1N1pdm09-HA2. Importantly, prior year vaccination of subjects receiving repeat vaccinations demonstrated reduced antibody-affinity maturation to HA1 of all three influenza virus strains irrespective of the vaccine platform. This study identifies an important impact of repeat vaccination on antibody-affinity maturation following vaccination, which may contribute to lower vaccine effectiveness of seasonal influenza vaccines in humans

Highlights

Several vaccines are approved in the United States for seasonal influenza vaccination every year
The Fluzone group had a higher percentage of subjects vaccinated in the previous year, and had a higher pre-vaccination baseline hemagglutination inhibition (HI) titer against H1N1
Since we observed clear trend for serum antibody affinity maturation following vaccination, in both years of the current study, (Fig. 3), we evaluated the impact of repeat vaccination on affinity maturation for the 16 individuals who received identical vaccine type in both the years across the three vaccine platforms

Summary

Introduction

Several vaccines are approved in the United States for seasonal influenza vaccination every year. We compare the impact of repeat influenza vaccination on hemagglutination inhibition (HI) titers, antibody binding and affinity maturation to individual hemagglutinin (HA) domains, HA1 and HA2, across vaccine platforms. While FluBlok contains pure HAs, the Fluzone and FluCelvax vaccines contain additional viral proteins (neuraminidase, NP, M1) as well as different host cellderived proteins, which are not measured routinely and are not included in the release specifications These viral and cellular proteins are likely to contribute to the immune response by eliciting antibodies, CD4, and CD8 T cell-specific responses. We report the HI titers and in-depth analyses of the realtime antibody-binding kinetics to individual HA domains, HA1 and HA2, using surface plasmon resonance (SPR) following vaccination with products manufactured using the three vaccine platforms and monitoring the impact of repeat/prior vaccination on the quality of the humoral immune response. Since antibodies are bivalent, the proper term for their binding to multivalent antigens like viruses is avidity, but here we use the term affinity throughout since we measured primarily monovalent interactions

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