Comparison of assays used to detect antibody response in COVID-19 vaccine trials: Results from of a UK multi-Centre randomised controlled trial to determine the immunogenicity responses of COVID-19 vaccines administered concomitantly with seasonal influenza vaccines (ComFluCOV)

Vaccine. 2024 Dec 2;42(26):126369. doi: 10.1016/j.vaccine.2024.126369. Epub 2024 Sep 23.

Abstract

Background: The ComFluCOV trial tested the safety and immunogenicity of COVID-19 and influenza vaccines co-administration. Binding and functional SARS-CoV2 anti-spike responses were measured using assays developed in response to the COVID-19 pandemic. The three assays used to measure the immunogenicity outcomes are reported here and their performance compared to inform future vaccine development.

Methods: Adults aged over 18 were vaccinated with a COVID-19 and either an influenza vaccine or saline placebo. Serum sampled one month after vaccination was used to measure SARS-CoV2 anti-spike antibody concentrations using a commercial in-house enzyme-linked immunosorbent assay (ELISA), a commercial fast throughput electrochemiluminescence immunoassay (ECLIA) and a viral neutralisation assay (VNA). Geometric mean ratios were used to compare the response to COVID-19 with or without influenza vaccine with a threshold of 0.67 considered non-inferior. The relationship between the different assays was examined using Kendall rank correlations.

Results: The geometric mean ratios exceeded 0.67 using all assays for all COVID-19 and influenza vaccine combinations tested. Moderate rank correlations were found between the three assays.

Conclusion: All three assays confirmed that vaccine co-administration did not significantly impact on immunogenicity of any of the vaccines tested.

Trial registration: ISRCTN14391248, registered on 17/03/2021.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral* / blood
  • Antibody Formation / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Humans
  • Immunogenicity, Vaccine
  • Influenza Vaccines* / administration & dosage
  • Influenza Vaccines* / immunology
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control
  • Male
  • Middle Aged
  • Neutralization Tests / methods
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / immunology
  • United Kingdom
  • Vaccination / methods
  • Young Adult

Substances

  • Influenza Vaccines
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus