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1.
Nat Commun ; 13(1): 4710, 2022 Aug 11.
Article in English | MEDLINE | ID: covidwho-1991589

ABSTRACT

Comparative analyses of the immunogenicity and reactogenicity of homologous and heterologous SARS-CoV-2 vaccine-regimens will inform optimized vaccine strategies. Here we analyze the humoral and cellular immune response following heterologous and homologous vaccination strategies in a convenience cohort of 331 healthy individuals. All regimens induce immunity to the vaccine antigen. Immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (n = 66) or mRNA-1273 (n = 101) is equivalent to or more pronounced than homologous mRNA-regimens (n = 43 BNT162b2, n = 59 mRNA-1273) or homologous ChAdOx1-nCoV-19 vaccination (n = 62). We note highest levels of spike-specific CD8 T-cells following both heterologous regimens. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 are higher than respective combinations with BNT162b2. Polyfunctional T-cell levels are highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens are well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming, and ChAdOx1-nCoV-19/mRNA-1273-boosting. In conclusion, we present comparative analyses of immunogenicity and reactogenicity for heterologous vector/mRNA-boosting and homologous mRNA-regimens.


Subject(s)
COVID-19 Vaccines , COVID-19 , 2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Humans , RNA, Messenger , SARS-CoV-2/genetics , Vaccination/adverse effects
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292372

ABSTRACT

Head-to-head analyses of immunogenicity and reactogenicity between the authorized homologous vaccine-regimens and heterologous combinations thereof are currently limited. Using a convenience cohort of 331 healthy individuals, we show that humoral and cellular immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (n=66) or mRNA-1273 (n=101) is equivalent or superior to homologous mRNA-regimens (n=43 BNT162b2, n=59 mRNA-1273), and more pronounced than after homologous ChAdOx1-nCoV-19 vaccination (n=62). Levels of spike-specific CD8 T cells were highest in both heterologous regimens, and significantly higher than all three homologous combinations. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 were higher than respective combinations with BNT162b2. Polyfunctional T-cell levels were highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens were well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming and mRNA-1273-boosting. In conclusion, immunogenicity after heterologous vector/mRNA-boosting and homologous mRNA-regimens is superior to homologous vector-regimens with notable differences between mRNA vaccines.

3.
Am J Transplant ; 21(12): 3990-4002, 2021 12.
Article in English | MEDLINE | ID: covidwho-1373780

ABSTRACT

Knowledge on the immunogenicity of vector-based and mRNA-vaccines in solid organ transplant recipients is limited. Therefore, SARS-CoV-2-specific T cells and antibodies were analyzed in 40 transplant recipients and 70 controls after homologous or heterologous vaccine-regimens. Plasmablasts and SARS-CoV-2-specific CD4 and CD8 T cells were quantified using flow cytometry. Specific antibodies were analyzed by ELISA and neutralization assay. The two vaccine types differed after the first vaccination, as IgG and neutralizing activity were more pronounced after mRNA priming (p = .0001 each), whereas CD4 and CD8 T cell levels were higher after vector priming (p = .009; p = .0001). All regimens were well tolerated, and SARS-CoV-2-specific antibodies and/or T cells after second vaccination were induced in 100% of controls and 70.6% of transplant recipients. Although antibody and T cell levels were lower in patients, heterologous vaccination led to the most pronounced induction of antibodies and CD4 T cells. Plasmablast numbers were significantly higher in controls and correlated with SARS-CoV-2-specific IgG- and T cell levels. While antibodies were only detected in 35.3% of patients, cellular immunity was more frequently found (64.7%) indicating that assessment of antibodies is insufficient to identify COVID-19-vaccine responders. In conclusion, heterologous vaccination seems promising in transplant recipients, and combined analysis of humoral and cellular immunity improves the identification of responders among immunocompromised individuals.


Subject(s)
COVID-19 , Organ Transplantation , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Humans , Immunity, Cellular , Immunity, Humoral , RNA, Messenger/genetics , SARS-CoV-2 , Transplant Recipients
4.
Nat Med ; 27(9): 1530-1535, 2021 09.
Article in English | MEDLINE | ID: covidwho-1327210

ABSTRACT

Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , Immunization, Secondary/methods , SARS-CoV-2/immunology , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19/prevention & control , Humans , Immunogenicity, Vaccine/immunology , Immunoglobulin G/blood , Spike Glycoprotein, Coronavirus/immunology , Vaccination
5.
JCI Insight ; 5(20)2020 10 15.
Article in English | MEDLINE | ID: covidwho-877604

ABSTRACT

BACKGROUNDPatients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2-specific immunity correlate with disease severity.METHODSIn this study, SARS-CoV-2-specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2-specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-γ, IL-2, and TNF-α) and markers for activation, proliferation, and functional anergy. SARS-CoV-2-specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls.RESULTSDespite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2-specific T cells as compared with convalescent individuals. SARS-CoV-2-specific CD4+ T cells dominated over CD8+ T cells and closely correlated with the number of plasmablasts and SARS-CoV-2-specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2-specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4+ and CD8+ T cells in general.CONCLUSIONGiven the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung.FUNDINGThe study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung.


Subject(s)
Antibodies, Viral , Betacoronavirus , Coronavirus Infections , Cytokines/blood , Leukocyte Count , Pandemics , Pneumonia, Viral , T-Lymphocytes , Adult , Antibodies, Viral/blood , Antibodies, Viral/classification , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , COVID-19 , Cardiovascular Diseases/epidemiology , Comorbidity , Coronavirus Infections/blood , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Correlation of Data , Critical Care/methods , Critical Care/statistics & numerical data , Critical Illness/therapy , Female , Germany/epidemiology , Humans , Leukocyte Count/methods , Leukocyte Count/statistics & numerical data , Lymphocyte Subsets/classification , Male , Metabolic Diseases/epidemiology , Middle Aged , Pneumonia, Viral/blood , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/classification , T-Lymphocytes/virology
6.
J Clin Med ; 9(6)2020 Jun 12.
Article in English | MEDLINE | ID: covidwho-603147

ABSTRACT

Health care systems worldwide have been facing major challenges since the outbreak of the SARS-CoV-2 pandemic. Kidney transplantation (KT) has been tremendously affected due to limited personal protective equipment (PPE) and intensive care unit (ICU) capacities. To provide valid information on risk factors for ICU admission in a high-risk cohort of old kidney recipients from old donors in the Eurotransplant Senior Program (ESP), we retrospectively conducted a bi-centric analysis. Overall, 17 (16.2%) patients out of 105 KTs were admitted to the ICU. They had a lower BMI, and both coronary artery disease (CAD) and hypertensive nephropathy were more frequent. A risk model combining BMI, CAD and hypertensive nephropathy gained a sensitivity of 94.1% and a negative predictive value of 97.8%, rendering it a valuable search test, but with low specificity (51.1%). ICU admission also proved to be an excellent parameter identifying patients at risk for short patient and graft survivals. Patients admitted to the ICU had shorter patient (1-year 57% vs. 90%) and graft (5-year 49% vs. 77%) survival. To conclude, potential kidney recipients with a low BMI, CAD and hypertensive nephropathy should only be transplanted in the ESP in times of SARS-CoV-2 pandemic if the local health situation can provide sufficient ICU capacities.

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