Antibody-Dependent Enhancement (ADE) and the role of complement system in disease pathogenesis

Thomas, Swapna; Smatti, Maria K.; Ouhtit, Allal; Cyprian, Farhan S.; Almaslamani, Muna; Thani, Asmaa A. Al; Yassine, Hadi M.

doi:10.1016/j.molimm.2022.11.010

“…Unfortunately, as of this writing, there is not data available on the long term impacts of Covid-19 vaccines, including effects resulting from rechallenge with the virus. Immune mediated danger from vaccines has been widely acknowledged to be an extant issue in the development of coronavirus vaccines [106][107][108][109][110][111][112], and is supported by current evidence [113].…”

Section: Harms Of Coronavirus Vaccinationmentioning

confidence: 88%

“…Immune mediated danger from vaccines has been widely acknowledged to be an extant issue in the development of coronavirus vaccines [106][107][108][109][110][111][112], and is supported by current evidence [113]. During the rapid development of Covid-19 vaccines, it was an issue of concern that sufficient long-term monitoring for antibody-dependent enhancement (ADE) effects be put into place [114,115].…”

Section: Harms Of Coronavirus Vaccinationmentioning

confidence: 98%

The Novelty of mRNA Vaccines and Potential Harms: A Scoping Review

Halma¹,

Rose²,

Lawrie³

2023

Preprint

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Pharmacovigilance databases are showing evidence of injury in the context of the COVID-19 modified mRNA shots. According to recent publications, adverse event reports linked to the mRNA COVID-19 products largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To assess the safety of current and future mRNA vaccines, further analysis on the risks due to the platform itself, and not specifically the expressed antigen. If harm can be exclusively and conclusively attributed to the spike protein, then it is possible that future mRNA vaccines expressing other antigens will be safe. If harms are attributable to the platform itself, then regardless of the toxicity, or lack thereof, of the chosen payload therein, the platform may be inherently unsafe, pending modification. In this work, we examine previous studies of RNA-based delivery by a lipid nanoparticle and break down the possible etiological elements of harm.

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“…Many genes connected with the immune system were also downregulated in all healthy people, such as IL6 (encoding interleukin 6), which stimulates antibody production [ 45 ], or IDO2 , which encodes indoleamine 2,3-dioxygenase 2, an enzyme that inhibits NK and T cell-induced cytotoxicity [ 46 ]. Surprisingly, the genes encoding components of the complement element 1q, C1QA (complement C1q A chain), C1QB (complement C1q B chain) and C1QC (complement C1q C chain) were also downregulated by 1,25D [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Immuno-Stimulating Activity of 1,25-Dihydroxyvitamin D in Blood Cells from Five Healthy People and in Blasts from Five Patients with Leukemias and Pre-Leukemic States

Marchwicka

¹

,

Nowak

²

,

Satyr

³

et al. 2023

IJMS

2

0

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(1) Hematological malignancies are characterized by an immortalization, uncontrolled proliferation of blood cells and their differentiation block, followed by the loss of function. The primary goal in the treatment of leukemias is the elimination of rapidly proliferating leukemic cells (named blasts). However, chemotherapy, which removes proliferating blasts, also prevents the remaining immune cells from being activated. Acute leukemias affect elderly people, who are often not fit to survive aggressive chemotherapy. Therefore, there is a need of milder treatment, named differentiation therapy, which might simulate the immune system of the patient. 1,25-Dihydroxyvitamin D, or low-calcemic analogs of this compound, were proposed as supporting therapy in acute leukemias. (2) Bone marrow blasts from patients with hematological malignancies, and leukocytes from healthy volunteers were ex vivo exposed to 1,25-dihydroxyvitamin D, and then their genomes and transcriptomes were investigated. (3) Our analysis indicates that 1,25-dihydroxyvitamin D regulates in blood cells predominantly genes involved in immune response, such as CAMP (cathelicidin antimicrobial peptide), CP (ceruloplasmin), CXCL9 (C-X-C motif chemokine ligand 9), CD14 (CD14 molecule) or VMO1 (vitelline membrane outer layer 1 homolog). This concerns blood cells from healthy people, as well as blasts from patients with hematological malignancies. In addition, in one patient, 1,25-dihydroxyvitamin D significantly downregulated transcription of genes responsible for cell division and immortalization. (4) In conclusion, the data presented in this paper suggest that addition of 1,25-dihydroxyvitamin D to the currently available treatments would stimulate immune system, inhibit proliferation and reduce immortal potential of blasts.

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“…Unfortunately, as of this writing, there is not data available on the long term impacts of Covid-19 vaccines, including effects resulting from rechallenge with the virus. Immune mediated danger from vaccines has been widely acknowledged to be an extant issue in the development of coronavirus vaccines [73][74][75][76][77][78][79], and is supported by current evidence [80]. During the rapid development of Covid-19 vaccines, it was an issue of concern that sufficient long-term monitoring for antibody-dependent enhancement (AD) effects be put into place [81,82].…”

Section: Harms Of Coronavirus Vaccinationmentioning

confidence: 98%

“…Furthermore, anti-spike IgG antibodies, as are produced by all of the mRNA vaccines, in addition to most other Covid-19 vaccines, are demonstrated to cause severe acute lung injury on re-exposure to the virus, suggesting a negative impact of a narrow immune response [71]. MERS-CoV vaccines have been tested in mice and rhesus macaques [72], revealing protection without visible histopathology Immune mediated danger from vaccines has been widely acknowledged to be an extant issue in the development of coronavirus vaccines [73][74][75][76][77][78][79], and is supported by current evidence [80]. During the rapid development of Covid-19 vaccines, it was an issue of concern that sufficient long-term monitoring for antibody-dependent enhancement (AD) effects be put into place [81,82].…”

Section: Harms Of Coronavirus Vaccinationmentioning

confidence: 99%

The Novelty of mRNA Vaccines and Potential Harms: A Scoping Review

Halma¹,

Rose²,

Jenks³

et al. 2023

Preprint

0

View full text Add to dashboard Cite

Pharmacovigilance databases are showing evidence of injury in the context of the COVID-19 modified mRNA shots. According to recent publications, adverse event reports linked to the mRNA COVID-19 products largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To assess the safety of current and future mRNA vaccines, further analysis on the risks due to the platform itself, and not specifically the expressed antigen. If harm can be exclusively and conclusively attributed to the spike protein, then it is possible that future mRNA vaccines expressing other antigens will be safe. If harms are attributable to the platform itself, then regardless of the toxicity, or lack thereof, of the chosen payload therein, the platform may be inherently unsafe, pending modification. In this work, we examine previous studies of RNA-based delivery by a lipid nanoparticle and break down the possible etiological elements of harm.

show abstract

Antibody-Dependent Enhancement (ADE) and the role of complement system in disease pathogenesis

Cited by 28 publications

References 137 publications

The Novelty of mRNA Vaccines and Potential Harms: A Scoping Review

The Novelty of mRNA Vaccines and Potential Harms: A Scoping Review

Immuno-Stimulating Activity of 1,25-Dihydroxyvitamin D in Blood Cells from Five Healthy People and in Blasts from Five Patients with Leukemias and Pre-Leukemic States

The Novelty of mRNA Vaccines and Potential Harms: A Scoping Review

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