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Age-related differences in humoral and cellular immune responses after primary immunisation: indications for stratified vaccination schedules.

ABSTRACT: Immunosenescence is characterised by reduced B and T cell responses. Evidence shows that booster vaccinations are less effective in elderly people, but data on the efficacy of primary immunisation are sparse. We conducted a monocentric, open label, phase IV trial to compare immune responses to primary vaccinations using the inactivated, adjuvanted Japanese Encephalitis vaccine by 30 elderly people (mean 69, range 61-78?years) and 30 younger people (mean 24, range 18-30?years). Humoral and cellular immune responses were analysed in relation to age and cytomegalovirus (CMV) seropositivity. Vaccine-specific antibody titres were significantly lower in elderly participants and 47% of them were non- or low responders after the two doses of the vaccine neo-antigen. The reduced humoral immune responses in elderly people correlated with reduced cytokine production, such as interferon gamma (IFN-?) in vitro, as well as higher frequencies of late-differentiated effector and effector memory T cells and T regulatory cells. These cellular changes and lower antibody titres were particularly prominent in CMV-seropositive elderly participants. If primary vaccination before the age of 60 is not possible, elderly patients may require different vaccination strategies to ensure sufficient long-lasting immunity, such as adapted or accelerated schedules and the use of different adjuvants.

SUBMITTER: Wagner A

PROVIDER: S-EPMC6026142 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Age-related differences in humoral and cellular immune responses after primary immunisation: indications for stratified vaccination schedules.

Wagner Angelika A Garner-Spitzer Erika E Jasinska Joanna J Kollaritsch Herwig H Stiasny Karin K Kundi Michael M Wiedermann Ursula U

Scientific reports 20180629 1

Immunosenescence is characterised by reduced B and T cell responses. Evidence shows that booster vaccinations are less effective in elderly people, but data on the efficacy of primary immunisation are sparse. We conducted a monocentric, open label, phase IV trial to compare immune responses to primary vaccinations using the inactivated, adjuvanted Japanese Encephalitis vaccine by 30 elderly people (mean 69, range 61-78 years) and 30 younger people (mean 24, range 18-30 years). Humoral and cellul ...[more]

PMID: 29959387

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Project description:BackgroundIndividual doses of dual-dose vaccine-regimens are sequentially administered into the deltoid muscle, but little attention has so far been paid to the immunological effects of choosing the ipsilateral or the contralateral side for the second dose.MethodsIn an observational study, 303 previously naive individuals were recruited, who received the second dose of the COVID-19 vaccine BNT162b2 on either the ipsilateral (n = 147) or the contralateral side (n = 156). Spike-specific IgG, IgG-avidity, and neutralizing antibodies were quantified using ELISA and a surrogate assay 2 weeks after dose 2. A subgroup of 143 individuals (64 ipsilateral, 79 contralateral) was analysed for spike-specific CD4 and CD8 T-cells using flow-cytometry.FindingsMedian spike-specific IgG-levels did not differ after ipsilateral (4590 (IQR 3438) BAU/ml) or contralateral vaccination (4002 (IQR 3524) BAU/ml, p = 0.106). IgG-avidity was also similar (p = 0.056). However, neutralizing activity was significantly lower after contralateral vaccination (p = 0.024). Likewise, median spike-specific CD8 T-cell levels were significantly lower (p = 0.004). Consequently, the percentage of individuals with detectable CD8 T-cells was significantly lower after contralateral than after ipsilateral vaccination (43.0% versus 67.2%, p = 0.004). Spike specific CD4 T-cell levels were similar in both groups, but showed significantly higher CTLA-4 expression after contralateral vaccination (p = 0.011). These effects were vaccine-specific, as polyclonally stimulated T-cell levels did not differ.InterpretationBoth ipsilateral and contralateral vaccination induce a strong immune response, but secondary boosting is more pronounced when choosing vaccine administration-routes that allows for drainage by the same lymph nodes used for priming. Higher neutralizing antibody activity and higher levels of spike-specific CD8 T-cells may have implications for protection from infection and severe disease and support general preference for ipsilateral vaccination.FundingFinancial support was provided in part by the State chancellery of the Saarland to M.S.

Project description:ObjectiveSARS-CoV-2 vaccinations have demonstrated vaccine-immunogenicity in healthy volunteers, however, efficacy in immunosuppressed patients is less well characterised. There is an urgent need to address the impact of immunosuppression on vaccine immunogenicity.MethodsSerological, T-cell ELISpot, cytokines and immunophenotyping were used to assess vaccine responses (either BNT162b2 mRNA or ChAdOx1 nCoV-19) in double-vaccinated patients receiving immunosuppression for renal transplants or haematological malignancies (n = 13). Immunological responses in immunosuppressed patients (VACC-IS) were compared to immunocompetent vaccinated (VACC-IC, n = 12), unvaccinated (UNVACC, n = 11) and infection-naïve unvaccinated (HC, n = 3) cohorts.ResultsNo significant different differences in T-cell responses were observed between VACC-IS and VACC-IC (92%) to spike-peptide (S) stimulation. UNVACC had the highest T-cell non-responders (n = 3), whereas VACC-IC and VACC-IS both had one T-cell non-responder. No significant differences in humoral responses were observed between VACC-IC and VACC-IS, with 92% (12/13) of VACC-IS patients demonstrating seropositivity. One VACC-IS failed to seroconvert, however had detectable T-cell responses. All VACC-IC participants were seropositive for anti-spike antibodies. VACC-IS and VACC-IC participants elicited strong Th1 cytokine response with immunodominance towards S-peptide. Differences in T-cell immunophenotyping were seen between VACC-IS and VACC-IC, with lower CD8+ activation and T-effector memory phenotype observed in VACC-IS.ConclusionSARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppressive therapy, with responses comparable to vaccinated immunocompetent participants. Lower humoral responses were seen in patients treated with B-cell depleting therapeutics, but with preserved T-cell responses. We suggest further work to correlate both protective immunity and longevity of these responses in both healthy and immunosuppressed patients.

Project description:BackgroundFew 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).MethodsIn 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.FindingsThe 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]).InterpretationThis 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.FundingDIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).

Project description:BackgroundThe Sinovac SARS-CoV-2 inactivated vaccine (CoronaVac) has been demonstrated to be safe, well tolerated, and efficacious in preventing mild and severe Covid-19. Although different studies have demonstrated its short-term immunogenicity, long-term cellular and humoral response evaluations are still lacking.MethodsCellular and humoral responses were assessed after enrollment of volunteers in the PROFISCOV phase 3 double-blind, randomized, placebo-controlled clinical trial to evaluate CoronaVac. Assays were performed using flow cytometry to evaluate cellular immune response and an antigen binding electrochemiluminescence assay to detect antigen-specific antibodies to the virus.ResultsFifty-three volunteers were selected for long term assessment of their SARS-CoV-2-specific immune responses. CD4 + T cell responses (including circulating follicular helper (cTfh, CD45RA - CXCR5 + ) expressing CD40L, as well as non-cTfh cells expressing CXCR3) were observed early upon the first vaccine dose, increased after the second dose, remaining stable for 6-months. Memory CD4 + T cells were detected in almost all vaccinees, the majority being central memory T cells. IgG levels against Wuhan/WH04/2020 N, S and receptor binding domain (RBD) antigens and the variants of concern (VOCs, including B.1.1.7/Alpha, B.1.351/Beta and P.1/Gamma) S and RBD antigens peaked 14 days after the second vaccine shot, and were mostly stable for a 1-year period.ConclusionsCoronaVac two-doses regimen is able to induce a potent and durable SARS-CoV-2 specific cellular response. The cellular reaction is part of a coordinated immune response that includes high levels of specific IgG levels against parental and SARS-CoV-2 VOC strains, still detected after one year.FundingFundação Butantan, Instituto Butantan and São Paulo Research Foundation (FAPESP) (grants 2020/10127-1 and 2020/06409-1). This work has also been supported by NIH contract 75N93019C00065 (A.S, D.W). PATH facilitated reagent donations for this work with support by the Bill & Melinda Gates Foundation (INV-021239). Under the grant conditions of the foundation, a Creative Commons Attribution 4.0 generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission.

Dataset Information

Age-related differences in humoral and cellular immune responses after primary immunisation: indications for stratified vaccination schedules.

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Age-related differences in humoral and cellular immune responses after primary immunisation: indications for stratified vaccination schedules.

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