Immunogenicity of concomitant SARS-CoV-2 and influenza vaccination in UK healthcare workers: a prospective longitudinal observational study

Joshua Nazareth; Christopher A Martin; Daniel Pan; Ian G Barr; Sheena G Sullivan; Heidi Peck; Neyme Veli; Mrinal Das; Luke Bryant; Nisha George; Marjan Gohar; Laura J Gray; Lucy Teece; Denny Vail; Val Renals; Aleesha Karia; Paul Renals; Paul Moss; Andrea Tattersall; Ashley D Otter; Pranab Haldar; Andrea Cooper; Iain Stephenson; Martin J Wiselka; Julian W Tang; Laura Nellums; Manish Pareek

doi:10.1016/j.lanepe.2024.101022

Immunogenicity of concomitant SARS-CoV-2 and influenza vaccination in UK healthcare workers: a prospective longitudinal observational study

Lancet Reg Health Eur. 2024 Aug 12:44:101022. doi: 10.1016/j.lanepe.2024.101022. eCollection 2024 Sep.

Authors

Joshua Nazareth^{1

2

3

4}, Christopher A Martin^{1

2

3

4}, Daniel Pan^{1

2

3

4

5

6}, Ian G Barr⁷, Sheena G Sullivan^{7

8

9}, Heidi Peck⁷, Neyme Veli¹, Mrinal Das¹, Luke Bryant^{1

3}, Nisha George^{1

2

3

4}, Marjan Gohar^{1

2

3

4}, Laura J Gray¹⁰, Lucy Teece¹⁰, Denny Vail¹¹, Val Renals¹¹, Aleesha Karia¹¹, Paul Renals¹¹, Paul Moss¹², Andrea Tattersall¹³, Ashley D Otter¹⁴, Pranab Haldar^{1

15}, Andrea Cooper^{1

3}, Iain Stephenson², Martin J Wiselka^{1

2}, Julian W Tang^{1

16}, Laura Nellums^{17

18}, Manish Pareek^{1

2

3

4}

Affiliations

¹ Department of Respiratory Sciences, University of Leicester, UK.
² Department of Infection and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK.
³ Leicester NIHR Biomedical Research Centre, Leicester, UK.
⁴ Development Centre for Population Health, University of Leicester, Leicester, UK.
⁵ Li Ka Shing Centre for Health Information and Discovery, Oxford Big Data Institute, University of Oxford, UK.
⁶ WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
⁷ WHO Collaborating Centre for Reference and Research on Influenza, Royal Melbourne Hospital, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
⁸ Department of Infectious Diseases, University of Melbourne, Melbourne, Australia.
⁹ Department of Epidemiology, University of California, Los Angeles, USA.
¹⁰ Department of Population Health Sciences, University of Leicester, UK.
¹¹ Research Space, University Hospitals of Leicester NHS Trust, UK.
¹² Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
¹³ Revvity (Certimmune), Abingdon, Oxfordshire, UK.
¹⁴ UK Health Security Agency, Porton Down, Salisbury, UK.
¹⁵ Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK.
¹⁶ Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, UK.
¹⁷ Lifespan and Population Health Academic Unit, School of Medicine, University of Nottingham, Nottingham, UK.
¹⁸ College of Population Health, University of New Mexico, NM, USA.

Abstract

Background: Co-administration of inactivated influenza vaccine (IIV) and SARS-CoV-2 vaccine may impact SARS-CoV-2 vaccine induced humoral immune responses. We aimed to compare IIV and SARS-CoV-2 vaccine induced cellular and humoral immune responses in those receiving concomitant vaccination to those receiving these vaccines separately.

Methods: We conducted a cohort study between 29th September 2021 and 5th August 2022 in healthcare workers who worked at the local NHS trust and in the surrounding area that were vaccinated with a mRNA SARS-CoV-2 booster and cell-based IIV. We measured haemagglutination inhibition assay (HAI) titres, SARS-CoV-2 anti-spike antibody and SARS-CoV-2 ELISpot count pre-vaccination, 1-month and 6-months post-vaccination and evaluated differences by vaccine strategy.

Findings: We recruited 420 participants, 234/420 (56%) were vaccinated concomitantly and 186/420 (44%) separately. The 1-month post-vaccination mean fold rise (MFR) in SARS-CoV-2 anti-spike antibodies was lower in those vaccinated concomitantly compared to separately (MFR [95% confidence interval (CI)] 9.7 [8.3, 11.4] vs 12.8 [10.3, 15.9], p = 0.04). After adjustment for age and sex, the adjusted geometric mean ratio (aGMR) remained lower for those vaccinated concomitantly compared to separately (aGMR [95% CI] 0.80 [0.70, 0.92], p = 0.001). At 6-months post-vaccination, we found no statistically significant difference in SARS-CoV-2 anti-spike antibody titres (aGMR [95% CI] 1.09 [0.87, 1.35], p = 0.45). We found no statistically significant correlation between vaccine strategy with SARS-CoV-2 ELISpot count and influenza HAI titres at 1-month and 6-months post-vaccination.

Interpretation: Our study found that concomitant vaccination with SARS-CoV-2 and IIV has no statistically significant impacts on long-term immunogenicity. Further research is required to understand the underlying mechanisms and assess the clinical significance of reduced anti-spike antibodies in those vaccinated concomitantly.

Funding: Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).

Keywords: Immunogenicity; Influenza; SARS-CoV-2; Vaccine co-administration.