Dataset Information

Comparison of Humoral Antibody Responses and Seroconversion Rates between Two Homologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination in Patients Undergoing Maintenance Hemodialysis.

ABSTRACT:

Background

Hemodialysis patients are at an increased risk of SARS-CoV-2 infection and are excluded from preauthorization COVID-19 vaccine trials; therefore, their immunogenicity is uncertain.

Methods

To compare the antibody responses to homologous ChAdOx1 and mRNA-1273 SARS-CoV-2 vaccination in hemodialysis patients, 103 age- and sex-matched hemodialysis patients with two homologous prime-boost vaccinations were recruited to detect anti-receptor-binding domain (RBD) IgG levels and seroconversion rates (SCRs) 14 days after a prime dose (PD14), before and 28 days after a boost dose (pre-BD0 and BD28).

Results

Both mRNA-1273 and ChAdOx1 vaccinations elicited immunogenicity in study subjects, and the former induced higher anti-RBD IgG levels than the latter. The SCRs of both groups increased over time and varied widely from 1.82% to 97.92%, and were significantly different at PD14 and pre-BD0 regardless of different thresholds. At BD28, the SCRs of the ChAdOx1 group and the mRNA-1273 group were comparable using a threshold ≥ 7.1 BAU/mL (93.96% vs. 97.92%) and a threshold ≥ 17 BAU/mL (92.73% vs. 97.92%), respectively, but they were significantly different using a threshold ≥ 20.2% of convalescent serum anti-RBD levels (52.73% vs. 95.83%). The seroconversion (≥20.2% of convalescent level) at BD28 was associated with mRNA-1273 vaccination after being adjusted for age, sex, body mass index, and the presence of solicited reactogenicity after a prime vaccination.

Conclusion

Our prospective, observational cohort indicates that a full prime-boost mRNA-1273 vaccination is likely to provide higher immune protection in hemodialysis patients compared to ChAdOx1, and this population with a prime-boost ChAdOx1 vaccination should be prioritized for a third dose.

SUBMITTER: Hsiao SH

PROVIDER: S-EPMC10383458 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Comparison of Humoral Antibody Responses and Seroconversion Rates between Two Homologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination in Patients Undergoing Maintenance Hemodialysis.

Hsiao Shih-Hsin SH Sue Yuh-Mou YM Kao Chih-Chin CC Chang Hui-Wen HW Lin Yen-Chung YC Hung Ching-Sheng CS Hsieh Yi-Chen YC Hong Shiao-Ya SY Chung Chi-Li CL Chang Jer-Hwa JH Su Ying-Shih YS Liu Ming-Che MC Lai Kevin Shu-Leung KS Chien Ko-Ling KL Wang Jude Chu-Chun JC Cheng Chung-Yi CY Fang Te-Chao TC

Vaccines 20230627 7

<h4>Background</h4>Hemodialysis patients are at an increased risk of SARS-CoV-2 infection and are excluded from preauthorization COVID-19 vaccine trials; therefore, their immunogenicity is uncertain.<h4>Methods</h4>To compare the antibody responses to homologous ChAdOx1 and mRNA-1273 SARS-CoV-2 vaccination in hemodialysis patients, 103 age- and sex-matched hemodialysis patients with two homologous prime-boost vaccinations were recruited to detect anti-receptor-binding domain (RBD) IgG levels and ...[more]

PMID: 37514977

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Project description:The ChAdOx1 nCoV-19 (AZD1222) vaccine is one of the most commonly delivered SARS-CoV-2 vaccines worldwide; however, few clinical studies have investigated its immunogenicity in dialysis patients. We prospectively enrolled 123 patients on maintenance hemodialysis at a medical center in Taiwan. All patients were infection-naive, had received two doses of the AZD1222 vaccine, and were monitored for 7 months. The primary outcomes were anti-SARS-CoV-2 receptor-binding domain (RBD) antibody concentrations before and after each dose and 5 months after the second dose and neutralization capacity against ancestral SARS-CoV-2, delta, and omicron variants. The anti-SARS-CoV-2 RBD antibody titers significantly increased with time following vaccination, with a peak at 1 month after the second dose (median titer, 498.8 U/mL; interquartile range, 162.5 to 1,050 U/mL), and a 4.7-fold decrease at 5 months. At 1 month after the second dose, 84.6, 83.7, and 1.6% of the participants had neutralizing antibodies against the ancestral virus, delta variant, and omicron variant, respectively, measured by a commercial surrogate neutralization assay. The geometric mean 50% pseudovirus neutralization titers for the ancestral virus, delta variant, and omicron variant were 639.1, 264.2, and 24.7, respectively. The anti-RBD antibody titers correlated well with neutralization capacity against the ancestral virus and delta variant. Transferrin saturation and C-reactive protein were associated with neutralization against the ancestral virus and delta variant. Although two doses of the AZD1222 vaccine initially elicited high anti-RBD antibody titers and neutralization against the ancestral virus and delta variant in hemodialysis patients, neutralizing antibodies against omicron variant were rarely detected, and the anti-RBD and neutralization antibodies waned over time. Additional/booster vaccinations are warranted in this population. IMPORTANCE Patients with kidney failure have worse immune response following vaccination compared to general population, but few clinical studies have investigated immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccination in hemodialysis patients. Here, we showed two doses of AZD1222 vaccines lead to high seroconversion rate of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies, and more than 80% patients acquired neutralizing antibodies against ancestral virus and delta variant. However, seldom did they obtain neutralizing antibodies against the omicron variant. The geometric mean 50% pseudovirus neutralization titer against the ancestral virus was 25.9-fold higher than that against the omicron variant. Also, there was a substantial decay in anti-RBD titers with time. Our findings provided evidence supporting that more protective measures, including additional/booster vaccinations, is warranted in these patients during the current COVID-19 pandemic.

Project description:Background and objectivesThe immunogenicity of vaccines is known to be attenuated in patients with end-stage kidney disease due to uremia. Patients on dialysis were excluded from coronavirus disease 2019 (COVID-19) vaccine trials; thus, the effectiveness of vaccines for this population is unclear. The aim of this study was to explore whether Asian dialysis patients can effectively produce an immune response after being vaccinated with the first dose of the ChAdOx1 nCoV-19 vaccine.Design setting, participants, and measurementsIn this prospective cohort study, we included Asian hemodialysis patients who received the ChAdOx1 nCoV-19 vaccine. At 3 weeks after the first dose of vaccination, we assessed the humoral immune response by measuring anti-SARS-CoV-2 S antibody titers. The primary outcome was the seropositive rate following vaccination, defined as an antibody titer greater than or equal to 0.8 U/ml. Factors associated with seropositivity were explored in multivariate logistic regression analyses.ResultsIn total, 434 participants were included. The mean age was 64 years, the mean dialysis vintage was 6 years, and 61% of the participants were men. At a mean time of 22 days from vaccination, 56% of the participants were seropositive. The vast majority (88%) had low antibody titers (< 15 U/ml). The multivariate logistic regression analyses showed that older age (every increase of 10 years, odds ratio [OR] 0.80, 95% CI 0.65-0.98, p = 0.03) was negatively associated with seropositivity and that higher Kt/V (every increase of 0.1, OR 1.14, 95% CI 1.01-1.28, p = 0.03) and higher serum albumin level (every increase of 0.1 g/dl, OR 1.09, 95% CI 1.02-1.18, p = 0.02) were positively associated with seropositivity.ConclusionsIn Asian hemodialysis patients, the seropositive rate was low, and most had low antibody titers after the first dose of the ChAdOx1 nCoV-19 vaccine. Younger age, better dialysis adequacy, and higher albumin levels were associated with seropositivity.

Project description:BackgroundVaccines are an important means to overcome the SARS-CoV-2 pandemic. They induce specific antibody and T-cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 180 days after homologous or heterologous vaccination with either ChAdOx1-nCoV-19 (ChAd) or BNT162b2 (BNT) or both.MethodsVarious tests were used to determine the humoral and cellular immune response. To quantify the antibody levels, we used the surrogate neutralization (sVNT) assay from YHLO, which we augmented with pseudo- and real virus neutralization tests (pVNT and rVNT). Antibody avidity was measured by a modified ELISA. To determine cellular reactivity, we used an IFN-γ Elispot, IFN-γ/IL Flurospot, and intracellular cytokine staining.FindingsAntibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neutralize SARS-CoV-2 - including variants of concern such as Delta or Omicron - was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer-lasting humoral immunity than homologous ChAd immunization. All vaccination regimens induced stable, polyfunctional T-cell responses.InterpretationThese findings demonstrate that heterologous vaccination with ChAd and BNT is a potent alternative to induce humoral and cellular immune protection in comparison to the homologous vaccination regimens.FundingThe study was funded by the German Centre for Infection Research (DZIF), the European Union's "Horizon 2020 Research and Innovation Programme" under grant agreement No. 101037867 (VACCELERATE), the "Bayerisches Staatsministerium für Wissenschaft und Kunst" for the CoVaKo-2021 and the For-COVID projects and the Helmholtz Association via the collaborative research program "CoViPa". Further support was obtained from the Federal Ministry of Education and Science (BMBF) through the "Netzwerk Universitätsmedizin", project "B-Fast" and "Cov-Immune". KS is supported by the German Federal Ministry of Education and Research (BMBF, 01KI2013) and the Else Kröner-Stiftung (2020_EKEA.127).

Dataset Information

Comparison of Humoral Antibody Responses and Seroconversion Rates between Two Homologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination in Patients Undergoing Maintenance Hemodialysis.

Background

Methods

Results

Conclusion

Publications

Comparison of Humoral Antibody Responses and Seroconversion Rates between Two Homologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination in Patients Undergoing Maintenance Hemodialysis.

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