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

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)

Deep immunophenotyping of peripheral blood cells in individuals exposed to Mycobacterium tuberculosis

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a worldwide public health issue. To control TB, we need prognostic tests to discriminate subjects infected but unlikely to succumb to disease (LTBI) from subjects developing disease (subclinical TB). To address this, we proposed that immunophenotyping could group LTBI from subclinical TB. We reasoned that in a high incidence, low exposure setting such as Leicester we would have a population of people wherein the immune response reflected the state of infection rather than the state of recent exposure to Mtb antigens. We therefore locally recruited 46 subjects designated as healthy unexposed (HC), active TB patients (ATB) or people with evidence of exposure but no clinical symptoms (latent tuberculosis infection, LTBI). We hypothesized that we could separate HC from ATB and that LTBI would be variable, reflecting the broad nature of the LTBI grouping. We compared the frequencies of specific cell types in peripheral blood mononuclear cells both ex vivo and post antigen-specific stimulation between these groups. We also compared the expression of inflammatory cytokines in plasma from the subjects. We developed an ELISA to determine the level of a novel biomarker of active TB, △TM-IL-12Rβ1. We found some individual characteristics were different for the ATB group compared to the other groups with more regulatory and antigen-specific T cells and fewer naïve CD4 T and NK cells. Principal component analysis showed that HC and ATB subjects could be grouped, while LTBI subjects were spread over the HC and ATB grouping. We have established a set of markers that can be used to group HC and ATB, we can now propose a longer follow up study to see whether any combination of these markers is an indicator of progression from latent to active TB.</p