Immunogenicity of standard, high-dose, MF59-adjuvanted, and recombinant-HA seasonal influenza vaccination in older adults

Athena P Y Li,Carolyn A Cohen,Vicky J Fang,Shivaprakash Gangappa,Benjamin J Cowling,A Danielle Iuliano,Suryaprakash Sambhara,Mark G Thompson,Min Z Levine,J S Malik Peiris,Ranawaka A P M Perera,Sophie A Valkenburg,Dennis K M Ip,Nancy H L Leung

doi:10.1038/s41541-021-00289-5

Abstract

The vaccine efficacy of standard-dose seasonal inactivated influenza vaccines (S-IIV) can be improved by the use of vaccines with higher antigen content or adjuvants. We conducted a randomized controlled trial in older adults to compare cellular and antibody responses of S-IIV versus enhanced vaccines (eIIV): MF59-adjuvanted (A-eIIV), high-dose (H-eIIV), and recombinant-hemagglutinin (HA) (R-eIIV). All vaccines induced comparable H3-HA-specific IgG and elevated antibody-dependent cellular cytotoxicity (ADCC) activity at day 30 post vaccination. H3-HA-specific ADCC responses were greatest following H-eIIV. Only A-eIIV increased H3-HA-IgG avidity, HA-stalk IgG and ADCC activity. eIIVs also increased polyfunctional CD4+ and CD8+ T cell responses, while cellular immune responses were skewed toward single-cytokine-producing T cells among S-IIV subjects. Our study provides further immunological evidence for the preferential use of eIIVs in older adults as each vaccine platform had an advantage over the standard-dose vaccine in terms of NK cell activation, HA-stalk antibodies, and T cell responses.

Highlights

Older adults (≥65 years) account for the majority of influenzarelated morbidity and mortality each year[1] and are considered a priority group for annual vaccination
Besides A-Enhanced inactivated influenza vaccines (eIIV) stimulating a greater proportion of high-avidity HA protein from A/ Switzerland/9715293/2013 (H3-2013) HA IgG and group 2 (G2)-stalk IgG compared to seasonal inactivated influenza vaccine (S-IIV), there were no significant differences in the induction of IgG response against another influenza A virus vaccine antigens between the vaccine groups (Fig. 1h and Supplementary Fig. 3f)
We found that A-eIIV stimulated an early increase in the proportion of high-avidity antibodies compared to S-IIV but it is not maintained long term, which has been observed by others[29]

Summary

INTRODUCTION

Older adults (≥65 years) account for the majority of influenzarelated morbidity and mortality each year[1] and are considered a priority group for annual vaccination. Enhanced inactivated influenza vaccines (eIIV) that induce greater hemagglutinin inhibition (HAI) titers to the immunodominant surface HA glycoprotein and confer superior immunogenicity and/or vaccine efficacy compared to S-IIV in preventing influenza-related medical complications have recently become available[3,4,5] These eIIVs, include Fluad (MF59-adjuvanted IIV, A-eIIV), fluzone-high-dose (IIV, H-eIIV), and Flublok (recombinant-HA IIV, R-eIIV). R-eIIV was superior when neutralizing antibody titers were assessed using cell-derived A (H3N2) virus, followed by H-eIIV and A-eIIV, and all eIIVs stimulated some boosting of T cell responses to multiple influenza virus strains In this current study, we further analyzed a subset of participants to determine whether improved immunogenicity following enhanced vaccination may be attributable to other humoral and cellular parameters besides HAI. A-eIIV elicited an early day 7 significant increase in G2 stalk-specific IgG (Fig. 1g), for which the magnitude of response was significantly greater than S-

Study design and population

DISCUSSION

METHODS

Study design and sampling