scholarly journals Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

2021 ◽  
Author(s):  
Michael Bonelli ◽  
Daniel Mrak ◽  
Selma Tobudic ◽  
Daniela Sieghart ◽  
Maximilian Koblischke ◽  
...  
Keyword(s):  
Immune Response ◽  
Cellular Immune Response ◽  
Controlled Trial ◽  
Seroconversion Rate ◽  
Booster Vaccination ◽  
Serious Adverse Events ◽  
Vector Vaccine ◽  
Vector Versus ◽  
Immunosuppressed Patients ◽  
Cellular Immune

ABSTRACTSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination. In this blinded randomized clinical trial (EudraCT 2021-002348-57) we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non-seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV-19 (Oxford-AstraZeneca). Patients were stratified according to the presence of peripheral B-cells. The primary efficacy endpoint was the difference in the SARS-CoV-2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week four. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at weeks one and four.Seroconversion rates at week four were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccine (p=0.6). Overall, 27% of patients seroconverted; specific T-cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. No serious adverse events, related to immunization, were observed. This enhanced humoral and/or cellular immune response supports an additional booster vaccination in non-seroconverted patients irrespective of a heterologous or homologous vaccination regimen.

scholarly journals Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomised controlled trial

2022 ◽  
pp. annrheumdis-2021-221558
Author(s):  
Michael Bonelli ◽  
Daniel Mrak ◽  
Selma Tobudic ◽  
Daniela Sieghart ◽  
Maximilian Koblischke ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Cellular Immune Response ◽  
Controlled Trial ◽  
Seroconversion Rate ◽  
Booster Vaccination ◽  
Vector Versus ◽  
Immunosuppressed Patients ◽  
Cellular Immune ◽  
Peripheral B Cells

ObjectivesSARS‐CoV‐2-induced COVID-19 has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination.MethodsIn this blinded randomised clinical trial, we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non-seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV-19 (Oxford–AstraZeneca). Patients were stratified according to the presence of peripheral B cells. The primary efficacy endpoint was the difference in the SARS-CoV-2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week 4. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at week 1 and week 4.ResultsSeroconversion rates at week 4 were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccines (p=0.6). Overall, 27% of patients seroconverted; specific T cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. 3/37 (8%) of patients without and 12/18 (67%) of the patients with detectable peripheral B cells seroconverted. No serious adverse events, related to immunisation, were observed.ConclusionsThis enhanced humoral and/or cellular immune response supports an additional booster vaccination in non-seroconverted patients irrespective of a heterologous or homologous vaccination regimen.

scholarly journals Enhancement of the Local CD8+ T-Cellular Immune Response to Mycobacterium tuberculosis in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1273
Author(s):  
Kirill Vasilyev ◽  
Anna-Polina Shurygina ◽  
Natalia Zabolotnykh ◽  
Mariia Sergeeva ◽  
Ekaterina Romanovskaya-Romanko ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Cellular Immune Response ◽  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Adaptive Immune Response ◽  
Reading Frame ◽  
Vector Vaccine ◽  
Specific Effector ◽  
Cellular Immune

BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of M.tb within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8+ lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by M.tb infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4+ and CD8+ T-lymphocytes.

scholarly journals PBMC transcriptomic responses to primary and secondary vaccination differ due to divergent lean growth and antibody titers in a pig model

2015 ◽  
Vol 47 (10) ◽  
pp. 470-478 ◽  
Author(s):  
Marcel Adler ◽  
Eduard Murani ◽  
Siriluck Ponsuksili ◽  
Klaus Wimmers
Keyword(s):  
Immune Response ◽  
Cellular Immune Response ◽  
High Performance ◽  
Booster Vaccination ◽  
Transcript Abundance ◽  
Cell Receptor ◽  
Growth Factor Signaling ◽  
Lean Growth ◽  
Antibody Titers ◽  
Cellular Immune

The genetic relationship between immune responsiveness and performance is not well understood, but a major topic of the evolution of resource allocation and of relevance in human medicine and livestock breeding, for instance. This study aims to show differences of transcript abundance changes during the time intervals before and after two tetanus toxoid (TT) vaccinations in domestic pigs differing in lean growth (LG) and anti-TT-antibody titers (AB) parameters of performance and immunocompetence. During response to the first vaccination all animals had a general decrease in transcript abundances related to various functional pathways as measured by comparative Affymetrix microarray hybridization and Ingenuity Pathway analyses. Low-AB phenotypes had predominantly decreased immune response transcripts. Combined phenotypes high-AB/high-LG had decreased transcripts related to growth factor signaling pathways. However, during the interval after the booster vaccination, high-LG and high-AB animals responded exclusively with increased immune transcripts, such as B-cell receptor signaling and cellular immune response pathways. In addition, high-LG and low-AB animals had predominantly increased transcripts of several cellular immune response pathways. Conversely, low-LG and high-AB animals had few elevated immune transcripts and decreased transcripts related to only two nonimmune-specific pathways. In response to booster vaccination high-LG phenotypes revealed enriched transcripts related to several different immune response pathways, regardless of AB phenotype. Different from the expected impact of AB titers, divergent AB phenotypes did not reflect considerable differences between immune transcripts. However, highly significant differences observed among divergent LG phenotypes suggest the compatibility of high performance and high vaccine responses.

Broad Antibody and Cellular Immune Response From a Phase 2 Clinical Trial With a Novel Multivalent Poxvirus-Based Respiratory Syncytial Virus Vaccine

2020 ◽  
Author(s):  
Elke Jordan ◽  
Steven J Lawrence ◽  
Thomas P H Meyer ◽  
Darja Schmidt ◽  
Stephanie Schultz ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Cellular Immune Response ◽  
Fold Increase ◽  
The Elderly ◽  
Surface Proteins ◽  
Phase 2 ◽  
Serious Adverse Events ◽  
Syncytial Virus ◽  
Cellular Immune

Abstract Background Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in young children and the elderly. Protective immunity is not generated after repeated infections, but vaccination may hopefully prove effective. Methods This phase 2 clinical study investigated a multivalent RSV vaccine (MVA-BN-RSV) designed to induce broad antibody and cellular immune responses by encoding RSV surface proteins F, G (for both A and B subtypes), and internal antigens (M2, N). This study evaluated the immune response in adults aged ≥55 years to identify the optimal MVA-BN-RSV dose and vaccination schedule. Results A single dose increased the levels of neutralizing (plaque reduction neutralization test to RSV A and B) and total (IgG and IgA ELISA) antibodies (1.6 to 3.4-fold increase from baseline) and induced a broad Th1-biased cellular immune response (interferon-γ ELISPOT) to all 5 vaccine inserts (5.4 to 9.7-fold increases). Antibody responses remained above baseline for 6 months. A 12-month booster dose elicited a booster effect in antibody and T-cell responses (up to 2.8-fold from preboost levels). No drug-related serious adverse events were reported. Conclusions MVA-BN-RSV induces a broad immune response that persists at least 6 months and can be boosted at 12 months, without significant safety findings. Clinical Trials Registration NCT02873286

Humoral and cellular immune response to a crude exo-antigen and purified keratinase of Microsporum canis in experimentally infected guinea pigs

1999 ◽  
Vol 37 (2) ◽  
pp. 123-129 ◽  
Author(s):  
B. R. Mignon ◽  
T. Leclipteux ◽  
CH. Focant ◽  
A. J. Nikkels ◽  
G. E. PIErard ◽  
...  
Keyword(s):  
Immune Response ◽  
Cellular Immune Response ◽  
Guinea Pigs ◽  
Microsporum Canis ◽  
Cellular Immune

The humoral and cellular immune response of sheep against Borna disease virus in endemic and non-endemic areas

2004 ◽  
Vol 146 (4) ◽  
pp. 159-172 ◽  
Author(s):  
D. Müller-Doblies ◽  
S. Baumann ◽  
P. Grob ◽  
A. Hülsmeier ◽  
U. Müller-Doblies ◽  
...  
Keyword(s):  
Immune Response ◽  
Disease Virus ◽  
Cellular Immune Response ◽  
Borna Disease Virus ◽  
Endemic Areas ◽  
Cellular Immune ◽  
Borna Disease

Does gamma knife surgery stimulate cellular immune response to metastatic brain tumors? A histopathological and immunohistochemical study

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 180-184 ◽  
Author(s):  
György T. Szeifert ◽  
Isabelle Salmon ◽  
Sandrine Rorive ◽  
Nicolas Massager ◽  
Daniel Devriendt ◽  
...  
Keyword(s):  
Immune Response ◽  
Brain Tumors ◽  
Gamma Knife ◽  
Cellular Immune Response ◽  
Lymphocytic Infiltration ◽  
Gamma Knife Surgery ◽  
Metastatic Brain Tumors ◽  
Content Type ◽  
Cellular Immune ◽  
Fine Print

Object. The aim of this study was to analyze the cellular immune response and histopathological changes in secondary brain tumors after gamma knife surgery (GKS). Methods. Two hundred ten patients with cerebral metastases underwent GKS. Seven patients underwent subsequent craniotomy for tumor removal between 1 and 33 months after GKS. Four of these patients had one tumor, two patients had two tumors, and one patient had three. Histological and immunohistochemical investigations were performed. In addition to routine H & E and Mallory trichrome staining, immunohistochemical reactions were conducted to characterize the phenotypic nature of the cell population contributing to the tissue immune response to neoplastic deposits after radiosurgery. Light microscopy revealed an intensive lymphocytic infiltration in the parenchyma and stroma of tumor samples obtained in patients in whom surgery was performed over 6 months after GKS. Contrary to this, extensive areas of tissue necrosis with either an absent or scanty lymphoid population were observed in the poorly controlled neoplastic specimens obtained in cases in which surgery was undertaken in patients less than 6 months after GKS. Immunohistochemical characterization demonstrated the predominance of CD3-positive T cells in the lymphoid infiltration. Conclusions. Histopathological findings of the present study are consistent with a cellular immune response of natural killer cells against metastatic brain tumors, presumably stimulated by the ionizing energy of focused radiation.

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