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Effects of elicited and pre-existing purified anti-Neu5Gc antibodies on human endothelial cells

ABSTRACT: Effects of elicited and pre-existing purified anti-Neu5Gc antibodies on human endothelial cells

PROVIDER: PRJNA481307 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7525260_1.fastq.gz	Fastqsanger.gz
	SRR7525260_2.fastq.gz	Fastqsanger.gz
	SRR7525270_1.fastq.gz	Fastqsanger.gz
	SRR7525270_2.fastq.gz	Fastqsanger.gz
	SRR7525280_1.fastq.gz	Fastqsanger.gz

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Effects of elicited and pre-existing purified anti-Neu5Gc antibodies on human endothelial cells

Project description:Human beings are unable to synthetize the glycolylated neuraminidic acid (Neu5Gc) following a mutation of the CMAH gene and diet induced anti-Neu5Gc antibodies develop in the first year of life. However, because humans can absorb Neu5Gc which deposits at low levels on endothelial cells (EC), activation of endothelium by anti-Neu5Gc has been raised. Understanding whether this interaction contributes to EC normal biology or may induce a potentially detrimental EC activation is crucial, particularly in patients developing elicited anti-Neu5Gc following introduction of animal derived molecules or bio-devices. Ten EC lines were cultured with immune-affinity purified anti-Neu5Gc from normal sera (diet induced) or sera harvested following rabbit-IgG infusion (elicited) anti-Neu5Gc. After a 4h-incubation of Neu5Gc loaded ECs at levels close to those of freshly harvested ECs, ECs were stimulated with both anti-Neu5Gc types and with or without human complement. Anti-Neu5Gc induce a differential expression (DE) of 967 out of expressed 12,208 genes, with transcript accumulation in 93%. Most DE transcripts are shared following activation by pre-existing or elicited anti-Neu5Gc. Compared to ATG pre-existing antibodies, elicited anti-Neu5Gc down-regulated 66 genes, involving master genes such as IL8, ICAM1, MAPKINASES or NFKb1. Furthermore, addition of elicited anti-Neu5Gc to non-heat inactivated sera down-regulated most of the transcripts mobilized by serum alone, including key transcripts involved in apoptosis, fitting with no increase in apoptotic cells. Altogether, the RNA profiling following culture of human ECs and anti-Neu5Gc suggests that pre-existing anti-Neu5Gc contribute to normal human EC homeostasis rather than to an inflammatory oriented transcriptome. Elicited anti-Neu5Gc do not also skew EC transcriptome toward inflammation either, but trigger the release cytokines or chemokines in culture supernatants.

2019-07-18 | GSE117146 | GEO

Passive Transfer of Vaccine-Elicited Antibodies Protects Against SIV in Rhesus Macaques

Project description:In this study, we show that passive transfer of purified antibodies from vaccinated macaques can protect naïve animals against SIVmac251 challenges. The protective signature included multiple antibody functions and correlated with upregulation of interferon pathways in the vaccinated animals. Adoptive transfer of purified IgG from the vaccinated animals with the most robust protective signatures provided partial protection against SIVmac251 challenges in naïve recipient rhesus macaques. These data demonstrate the protective efficacy of purified vaccine-elicited antiviral antibodies, even in the absence of virus neutralization.

2020-08-14 | GSE156177 | GEO

Pre-existing cell states predict resistance to multiple treatments

Project description:Pre-existing cell states predict resistance to multiple treatments

| PRJNA1171004 | ENA

IL1β-dependent extravasation of pre-existing lung-restricted autoantibodies activates complement to promote primary graft dysfunction

Project description:Pre-existing lung restricted autoantibodies (LRA) are associated with a higher incidence of primary graft dysfunction (PGD) although it remains unclear whether LRA can drive its pathogenesis. In syngeneic murine left lung transplant recipients, pre-existing LRA worsened graft dysfunction, which was evident by impaired gas exchange, increased pulmonary edema, and activation of damage-associated pathways in lung epithelial cells. LRA-mediated injury was distinct from ischemia-reperfusion injury since deletion of donor non-classical monocytes as well as host neutrophils could not prevent graft dysfunction in LRA-pretreated recipients. Whole LRA IgG molecule was necessary for lung injury which was mediated by the classical and alternative complement pathways and reversed by complement inhibition. However, deletion of Fc receptors in donor macrophages or mannose-binding lectin proteins failed to rescue lung function. LRA- mediated injury was localized to the transplanted lung and dependent on IL1β-mediated permeabilization of pulmonary vascular endothelium which allowed extravasation of antibodies. Genetic deletion or pharmacological inhibition of IL1R in the donor lungs prevented LRA-induced graft injury. In humans, pre-existing LRA was an independent risk factor for severe PGD and could be treated with plasmapheresis and complement blockade. We conclude that pre-existing LRA can compound ischemia-reperfusion injury to worsen PGD for which complement inhibition may be effective.

2022-10-19 | GSE211501 | GEO

Passive Transfer of Vaccine-Elicited Antibodies Protects Against SIV in Rhesus Macaques

Project description:Passive Transfer of Vaccine-Elicited Antibodies Protects Against SIV in Rhesus Macaques

| PRJNA657000 | ENA

Pre-existing cross-reactive antibody responses do not significantly impact inactivated COVID-19 vaccine-induced neutralization

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2021-10-13 | E-MTAB-11084 | biostudies-arrayexpress

Pre-existing cross-reactive antibody responses do not significantly impact inactivated COVID-19 vaccine-induced neutralization

2021-10-29 | E-MTAB-11117 | biostudies-arrayexpress

Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity

Project description:Currently available COVID-19 vaccines include inactivated virus, live attenuated virus, mRNA-based, viral vectored and adjuvanted protein-subunit-based vaccines. All of them contain the spike glycoprotein as the main immunogen and result in reduced disease severity upon SARS-CoV-2 infection. While we and others have shown that mRNA-based vaccination reactivates pre-existing, cross-reactive immunity, the effect of vector vaccines in this regard is unknown. Here, we studied cellular and humoral responses in heterologous adenovirus-vector-based ChAdOx1 nCOV-19 (AZ; Vaxzeria, AstraZeneca) and mRNA-based BNT162b2 (BNT; Comirnaty, BioNTech/Pfizer) vaccination and compared it to a homologous BNT vaccination regimen. AZ primary vaccination did not lead to measurable reactivation of cross-reactive cellular and humoral immunity compared to BNT primary vaccination. Moreover, humoral immunity induced by primary vaccination with AZ displayed differences in linear spike peptide epitope coverage and a lack of anti-S2 IgG antibodies. Contrary to primary AZ vaccination, secondary vaccination with BNT reactivated pre-existing, cross-reactive immunity, comparable to homologous primary and secondary mRNA vaccination. While induced anti-S1 IgG antibody titers were higher after heterologous vaccination, induced CD4+ T cell responses were highest in homologous vaccinated. However, the overall TCR repertoire breadth was comparable between heterologous AZ-BNT-vaccinated and homologous BNT-BNT-vaccinated individuals, matching TCR repertoire breadths after SARS-CoV-2 infection, too. The reasons why AZ and BNT primary vaccination elicits different immune response patterns to essentially the same antigen, and the associated benefits and risks, need further investigation to inform vaccine and vaccination schedule development.

2023-01-16 | GSE222872 | GEO

Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity

Project description:Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity

| PRJNA923688 | ENA

Reversal of pre-existing NGFR-driven tumor and immune therapy resistance

Project description:Reversal of pre-existing NGFR-driven tumor and immune therapy resistance

| PRJNA613021 | ENA