Immunogenicity of concomitant SARS-CoV-2 and influenza vaccination in UK healthcare workers: a prospective longitudinal observational study
Joshua Nazareth, Christopher Martin, Daniel Pan, Ian Barr, Sheena G. Sullivan, Heidi Peck, Neyme Veli, Mrinal K. 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 Otter, Pranabashis Haldar, Andrea M. Cooper, Iain Stephenson, Martin Wiselka, Julian W. Tang, Laura B Nellums, Manish Pareek
Abstract
BackgroundCo-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.MethodsWe 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.FindingsWe 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.InterpretationOur 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.FundingResearch and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).