Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis

Abstract

Background: Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs).

Methods: In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine.

Findings: The total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were from ethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06-2.06], P = 0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05-2.89], P = 0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178-12,852] vs 5888 BAU/ml [5023-6902], P = 0.008 and 2851 95% CI [1811-4487] vs 1199 [984-1462], P < 0.001 respectively), increments which persisted after adjustment (aGMR 1.26, 95% CI [1.01-1.58], P = 0.04 and aGMR 2.01, 95% CI [1.34-3.01], P = 0.001). SARS-CoV-2 ELISpot responses to S1 and whole spike peptides (S1 + S2 response) were higher in HCWs from South Asian ethnic groups than those from White groups (S1: aIRR 2.33, 95% CI [1.09-4.94], P = 0.03; spike: aIRR, 2.04, 95% CI [1.02-4.08]).

Interpretation: This study provides evidence that, in an infection naïve cohort, humoral and cellular immune responses to SARS-CoV-2 vaccination are stronger in South Asian HCWs than White HCWs. These differences are most clearly seen in the early period following vaccination. Further research is required to understand the underlying mechanisms, whether differences persist with further exposure to vaccine or virus, and the potential impact on vaccine effectiveness.

Funding: DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).

Keywords: COVID-19; Ethnicity; Heathcare worker; SARS-CoV-2; Vaccine.

Fig. 1

Formation of the analysed cohort. Fig. 1 shows how the final number of observations in each analysis were derived. The number of observations included in the analyses conducted in the subcohort whose sample was collected within 50 days of a second vaccine dose are detailed in the relevant figures/tables. There are 40 participants who were enrolled into both studies. For clarity, these participants are included in the figures for DIRECT. ∗Excluded from all analyses as no data on anti-nucleocapsid antibody status. † included in sensitivity analysis of neutralising activity data.

Fig. 2

Comparison of total SARS-CoV-2 spike-specific antibody titres by ethnic group and vaccine type. Fig. 2 shows a comparison of log10 total SARS-CoV-2 anti-spike antibody titres (BAU/ml), stratified by by ethnic group and vaccine type. Panels A, B and C include all participants. Panels D, E and F include only those sampled within 50 days of second vaccine dose. Panel G shows geometric mean titres (GMTs) and their 95% confidence intervals with the number of participants in each ethnic group for panels A–F. Groups were compared (with the White group as reference) using unpaired t tests. ∗P < 0.05, ∗∗P < 0.01.

Fig. 3

Comparison of serum SARS-CoV-2 neutralising antibody titre by ethnic group and vaccine type. Fig. 3 shows a comparison of log10 mean titre for 50% neutralisation from the pseudotype-based neutralisation assay stratified by ethnic group and vaccine type. Panels A, B and C include all participants. Panels D, E and F include only those sampled within 50 days of second vaccine dose. Panel G shows geometric mean titres (GMTs) and their 95% confidence intervals with the number of participants in each ethnic group for panels A–F. Groups were compared (with the White group as reference) with unpaired t tests. ∗∗∗P < 0.001.

Fig. 4

Comparison of T cell responses to SARS-CoV-2 S1, S2 and spike (S1 + S2) epitopes by ethnic group. Fig. 4 shows results from the ELISpot assay. Results are expressed as spot forming units (SFU/10⁶ PBMCs) in response to peptides derived from SARS-CoV-2 spike protein (regions S1, S2 and spike [S1 + S2]) stratified by ethnic group. Panels A, B and C include all participants. Panels D, E and F include only those sampled within 50 days of second vaccine dose. Panel G shows median (IQR) SFU/10⁶ PBMCs for each ethnic group in panels A–F. Groups were compared (with the White group as reference) with Wilcoxon rank sum tests. ∗P < 0.05.