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Humoral immune response to authentic circulating severe acute respiratory syndrome coronavirus 2 variants elicited by booster vaccination with distinct receptor-binding domain subunits in mice.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants could induce immune escape by mutations of the spike protein which are threatening to weaken vaccine efficacy. A booster vaccination is expected to increase the humoral immune response against SARS-CoV-2 variants in the population. We showed that immunization with two doses of wild type receptor-binding domain (RBD) protein, and booster vaccination with wild type or variant RBD protein all significantly increased binding and neutralizing antibody titers against wild type SARS-CoV-2 and its variants in mice. Only the booster immunization by Omicron (BA.1)RBD induced a strong antibody titer against the omicron virus strain and comparable antibody titers against all the other virus strains. These findings might shed the light on coronavirus disease 2019 booster immunogens.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC9347575 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Humoral immune response to authentic circulating severe acute respiratory syndrome coronavirus 2 variants elicited by booster vaccination with distinct receptor-binding domain subunits in mice.

Jiang Yushan Y Zhang Huan H Yu Jianhai J Huang Dong D Zhai Linlin L Li Mengjun M Wang Yuelin Y Ren Zuning Z Zou Lirong L Zheng Zhonghua Z Hu Huanyu H Zhang Junfang J Zhang Bao B Zhao Wei W Yang Xingfen X Li Baisheng B Shen Chenguang C

Journal of medical virology 20220603 9

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants could induce immune escape by mutations of the spike protein which are threatening to weaken vaccine efficacy. A booster vaccination is expected to increase the humoral immune response against SARS-CoV-2 variants in the population. We showed that immunization with two doses of wild type receptor-binding domain (RBD) protein, and booster vaccination with wild type or variant RBD protein all significantly increased binding and n ...[more]

PMID: 35614018

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Project description:End-stage renal disease (ESRD) patients are amongst the vulnerable groups and thus prioritized in the Coronavirus disease-2019 vaccination programmes. However, this cohort was excluded from vaccine-trials and yet shares the same vaccination scheme with the general population. Here, we explore trends of immune response-proportions amongst ESRD patients on renal replacement therapy for up to 4 weeks post-vaccination completion with Pfizer/Moderna vaccines. From inception to 10 July 2021, we searched six online-databases for articles reporting humoral and cellular immune response proportions for up to 4 weeks post booster-vaccination. We pooled the responders' proportions by meta-analysis and conducted a meta-regression stratifying outcomes by significant confounders. Twenty-seven eligible studies reported 2789 ESRD patients. 1337, 1452 and 477 were on haemodialysis, received kidney transplantation, and healthy controls, respectively. Haemodialysis patients' proportions of humoral and cellular immune responses varied from 87.29% (80.77-93.81)-88.78% (86.76-90.80) and 62.86% (56.56, 69.17)-85.78% (78.99, 92.57), respectively, between first- and fourth-weeks. Kidney transplant patients' proportions of humoral and cellular immune responses ranged from 2.6% (0.06-13.48)-29.87% (27.68, 32.07) and 5.13% (0.63-17.3)-59.84% (54.57-65.10), respectively, between first- and fourth-weeks. All healthy controls maintained ≥93% proportions of both responses throughout the follow-up. Study design and country of study influenced the pooled response proportions. Conclusively, haemodialysis and kidney transplant patients have lower proportions of humoral and cellular immune responses than healthy controls. However, haemodialysis patients' response proportions improve, reaching near healthy-control levels by the fourth week. Kidney transplant patients' lower responses' proportions also improve but remain significantly lower than healthy controls throughout four-weeks. The "one-size-fits-all" vaccination scheme might be inadequate for kidney transplant patients.

Project description:Background and aimsDialysis patients are extremely vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with high rates of hospitalization and mortality rates. In January 2021, the University of Virginia Dialysis Program initiated a program-wide vaccination campaign to administer the Pfizer BioNTech messenger RNA SARS-CoV-2 (BNT162b2) vaccine. The aim of this study was to characterize the long-term time-dependent decline in humoral immunity in hemodialysis patients.MethodsA prospective cohort study measuring serial monthly semiquantitative IgG antibody levels to the SARS-CoV-2 spike protein receptor binding domain in fully vaccinated in-center hemodialysis patients. Samples were collected monthly and tested for anti-SARS-CoV-2 antibodies against the anti-spike S1 domain for 2-6 months post full vaccination. Results were presented as internationally harmonized binding antibody units (BAU/ml). To analyze the change in antibody levels over time, a linear mixed model with random intercept and random slope was used for longitudinal antibody levels. A multivariable model was used to estimate the slope of antibody levels by adjusting for selected patient characteristics. Based on the estimated intercepts and slopes for each subject from the unadjusted model, 10-month antibody levels were projected.ResultsThe mean baseline antibody level was 647.59 BAU/ml and 87.88% (29/33) of patients were considered qualitatively positive. Two patients were negative at baseline and an additional two had borderline results. Patient antibody levels declined at an adjusted average rate of 31% per month. At 6 months postvaccination, 40% of patients remaining in the cohort possessed either negative or borderline IgG antibody levels. Projecting future antibody levels suggests that 65% of the cohort will progress to borderline or negative antibody levels at 10 months post full vaccination.ConclusionThe long-term vaccine response following vaccination with the BNT162b2 in hemodialysis patients was characterized. Our data add to the limited pool of data in this patient population and emphasize the critical need for vaccine boosters.

Dataset Information

Humoral immune response to authentic circulating severe acute respiratory syndrome coronavirus 2 variants elicited by booster vaccination with distinct receptor-binding domain subunits in mice.

Publications

Humoral immune response to authentic circulating severe acute respiratory syndrome coronavirus 2 variants elicited by booster vaccination with distinct receptor-binding domain subunits in mice.

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