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. 2024 Aug 12:44:101022.
doi: 10.1016/j.lanepe.2024.101022. eCollection 2024 Sep.

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

Joshua Nazareth  1   2   3   4 , Christopher A Martin  1   2   3   4 , Daniel Pan  1   2   3   4   5   6 , Ian G Barr  7 , Sheena G Sullivan  7   8   9 , Heidi Peck  7 , Neyme Veli  1 , Mrinal Das  1 , Luke Bryant  1   3 , Nisha George  1   2   3   4 , Marjan Gohar  1   2   3   4 , Laura J Gray  10 , Lucy Teece  10 , Denny Vail  11 , Val Renals  11 , Aleesha Karia  11 , Paul Renals  11 , Paul Moss  12 , Andrea Tattersall  13 , Ashley D Otter  14 , Pranab Haldar  1   15 , Andrea Cooper  1   3 , Iain Stephenson  2 , Martin J Wiselka  1   2 , Julian W Tang  1   16 , Laura Nellums  17   18 , Manish Pareek  1   2   3   4
Affiliations

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

Joshua Nazareth et al. Lancet Reg Health Eur. .

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.

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Conflict of interest statement

PM has received honoraria from Moderna, BioNTech, Gilead, AstraZeneca and GSK, support for attending meetings from AstraZeneca and has participated on an advisory board for AstraZeneca and Moderna. IB declares shares in an influenza vaccine manufacturing company. PH received an honorarium for hosting a COVID-19 webinar, on behalf of Oxford Immunotec (now Revvity) who are manufacturers of the ELISpot technology used in the manuscript. AT is an employee of Revvity. MP reports grants from UKRI-MRC for the current work and UKRI-MRC, NIHR, Sanofi, Gilead and Moderna outside the current work and has received consulting fees from QIAGEN. SGS reports consultancy or advisory role for CSL Seqirus, Novavax, Moderna, Sanofi and Evo Health. The WHO Collaborating Centre for Reference and Research on Influenza received funding from the International Federation of Pharmaceutical Manufacturers and Associations and from CSL Seqirus for the production of influenza vaccines. DP is supported by a NIHR Doctoral Research Fellowship. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Figures

Fig. 1
Fig. 1
Flowchart illustrating the analysed cohort. Flowchart of study participants included in the analysed cohort: 1-month post-vaccine and 6-months postvaccine for influenza immune responses and 1-month post-booster and 6-months post-booster for SARS-CoV-2 immune responses.
Fig. 2
Fig. 2
Comparison of mean fold rise in SARS-CoV-2 anti-spike antibody titres by vaccine strategy. Comparison of mean fold rise in SARS-CoV-2 anti-spike antibody titres between (a) pre- and 1-month post-booster and (b) 1-month post-booster to 6-months post-booster with the SARS-CoV-2 booster stratified by vaccine strategy. The table (c) shows the geometric mean fold rise and corresponding 95% confidence intervals between pre- and 1-month post-booster and 1-month post-booster to 6-months post-booster SARS-CoV-2 antispike antibody titres stratified by vaccine strategy. The two vaccine strategy groups were compared using an unpaired t test. MFR, mean fold rise; CI, confidence interval; ∗p value < 0.05.
Fig. 3
Fig. 3
Linear regression models showing the association between vaccine strategy and other parameters with ln SARS-CoV-2 post-booster anti-spike antibody titre. Linear regression models showing the association between vaccine strategy, previous anti-spike antibody titre, age and sex with natural logarithm (ln) SARS-CoV-2 anti-spike 1-month and 6-months post-booster titres. Results are shown for a fully adjusted model (red) which included all variables and a simplified model (blue) which just adjusted for vaccine strategy and previous anti-spike titre.
Fig. 4
Fig. 4
Negative binomial regression model showing the association between vaccine strategy and other parameters with S1, S2 and Spike specific T cell responses. Negative binomial regression models showing the association between vaccine strategy, previous ELISpot count, age and sex with ELISpot count in response to peptides derived from SARS-CoV-2 S1, S2 and spike (S1 + S2) 1-month post-booster and 6-months post-booster. Results are shown for a fully adjusted model (red) which included all variables and a simplified model (blue) which just adjusted for vaccine strategy and previous ELISpot count.
Fig. 5
Fig. 5
Comparison of mean fold rise in HAI titres by vaccine strategy. Comparison of mean fold rise in Haemagglutinin inhibition assay (HAI) titres between (a) pre- and 1- month post-vaccination and (b) 1-month and 6-months post-vaccination with the influenza vaccine stratified by vaccine strategy for each strain of influenza contained in the vaccine. Bars indicate the 95% CI, The table (c) shows the mean fold rise and corresponding 95% confidence intervals between pre- and post-vaccination and post-vaccination to 6-months post-vaccination HAI titres stratified by vaccine strategy for each strain of influenza. The two vaccine strategy groups were compared using an unpaired t test. MFR, mean fold rise; CI, confidence interval.
Fig. 6
Fig. 6
Linear regression models showing the association between vaccine strategy and other parameters with ln HAI post-vaccine titre. Linear regression models showing the association between vaccine strategy, previous haemagglutinin inhibition assay (HAI) titre, age and sex with natural logarithm (ln) HAI 1-month and 6-months post-vaccine titres for each influenza strain. Results are shown for a fully adjusted model (red) which included all variables and a simplified model (blue) which just adjusted for vaccine strategy and previous HAI titre.
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