Improved Resolution of Influenza Vaccination Responses With High-Throughput Live Virus Microneutralisation

Area of Science:

• Virology and Immunology
• Vaccinology
• Serological Assays

Background:

• Influenza poses a significant threat to human and animal health.
• Haemagglutinin inhibition (HAI) assays are traditionally used to assess serological protection against influenza, informing vaccine decisions and systems vaccinology.
• There is a need for advanced methods to better evaluate immune responses to influenza.

Purpose of the Study:

• To adapt a high-throughput live virus microneutralisation (LV-N) assay for influenza.
• To benchmark the adapted LV-N assay against traditional HAI assays.
• To report serological vaccine responsiveness in older adults using the new assay.

Main Methods:

• Assessed influenza-specific antibody responses in 73 individuals before and after receiving the 2021-22 quadrivalent influenza vaccine.
• Performed both HAI and LV-N assays against all four vaccine strains using sera collected at multiple time points.
• Compared serological responses within and between the HAI and LV-N assays.

Main Results:

• Both HAI and high-throughput LV-N assays detected vaccine-induced antibody titre boosts.
• High concordance was observed between the two assays (Spearman's correlation coefficient range 0.49-0.88).
• The LV-N assay provided improved granularity for estimating response fold changes and quantifying pre-existing antibody effects.

Conclusions:

• The high-throughput LV-N assay is a viable alternative for assessing influenza-specific serological responses with enhanced resolution.
• This method can improve annual assessment of antibody landscapes and evaluation of new vaccine strains.
• The assay offers potential advancements for systems vaccinology and laboratory-based pandemic preparedness.