B cell-derived cfDNA after primary BNT162b2 mRNA vaccination anticipates memory B cells and SARS-CoV-2 neutralizing antibodies

Fox-Fisher, Ilana; Piyanzin, Sheina; Briller, Mayan; Oiknine‐Djian, Esther; Alfi, Or; Ben-Ami, Roni; Peretz, Ayelet; Neiman, Daniel; Ochana, Bracha-Lea; Fridlich, Ori; Drawshy, Zeina; Klochendler, Agnes; Magenheim, Judith; Share, Danielle; Avrahami, Ran; Ribak, Yaarit; Talmon, Aviv; Rubin, Limor; Milman, Neta; Segev, Meital; Feldman, Erik; Tal, Yuval; Shen-Orr, Shai S.; Gläser, Benjamin; Shemer, Ruth; Wolf, Dana; Dor, Yuval

doi:10.1016/j.medj.2022.05.005

Cited by 6 publications

(6 citation statements)

References 41 publications

(63 reference statements)

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“…19,20 Another study found that booster vaccinations increase circulating cell-free DNA in B cells, T cells, and monocytes. 21 Therefore, it can be speculated that mRNA vaccination in uences autoimmunity, contributing to SLE development. Our study found that the risk for SLE was higher in the vaccinated group regardless of sex.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Risk of Autoimmune Diseases After mRNA-based COVID-19 Vaccination: A Korean Population-based Nationwide Cohort Study

Lee,

Jung,

Jeon

et al. 2024

Preprint

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The long-term association between mRNA-based Coronavirus Disease 2019 (COVID-19) vaccination and the development of autoimmune connective tissue diseases (AI-CTDs) remains unclear. In this nationwide population-based cohort study involving 9,258,803 individuals, we investigated the incidence of AI-CTDs associated with mRNA vaccines for ≥1 year and further analysed the risk by stratifying by sex, age, mRNA vaccine type, COVID-19 diagnosis, cross-vaccination with a non-mRNA vaccine, and booster vaccination. The risk of developing most AI-CTDs did not increase following mRNA vaccination. However, systemic lupus erythematosus and bullous pemphigoid were significantly more prevalent in vaccinated individuals than in controls. Comparable results were reported in the subgroup analyses, especially in the subgroups comprising women or patients aged ≥40 years who showed a higher risk of developing bullous pemphigoid following mRNA vaccination. Our results suggest that mRNA-based COVID-19 vaccinations are not associated with a high incidence of most AI-CTDs. However, further research is needed regarding its potential association with certain conditions including systemic lupus erythematosus and bullous pemphigoid.

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Section: Discussionmentioning

confidence: 99%

Long-Term Risk of Autoimmune Diseases After mRNA-based COVID-19 Vaccination: A Korean Population-based Nationwide Cohort Study

Lee,

Jung,

Jeon

et al. 2024

Preprint

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“…In addition, I have focused on the mechanisms in order to discuss all interpretations of pro-inflammatory and immunogenic effects of DNA, because detrimental innate immune activation and inflammation represent the shared element between HIV-1, COVID-19 and adverse vaccine effects. For example alternative interpretations leading to different conclusions exist even for the observation of elevated levels of cfDNA in vaccinee plasma, which has been interpreted as a favourable indicator of the formation of memory B cells after vaccination ( 127 ). In general, we must not forget that DNA-induced inflammation and pyroptotic cell death usually represent adaptive immune responses which benefit the host.…”

Section: Drawbacks and Limitations Of The Present Workmentioning

confidence: 99%

“…Multiple reports on elevated levels of anti-dsDNA antibodies in the plasma of vaccinees ( 126 – 132 ) indicate that increased cfDNA levels might be common in this group, although direct evidence for elevated levels of cfDNA in plasma of vaccinated individuals is scarce (but see ( 127 )).…”

Section: Introductionmentioning

confidence: 99%

Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies

Heil

2024

Front. Immunol.

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The coronavirus disease 2019 (COVID-19) pandemic triggered an unprecedented concentration of economic and research efforts to generate knowledge at unequalled speed on deregulated interferon type I signalling and nuclear factor kappa light chain enhancer in B-cells (NF-κB)-driven interleukin (IL)-1β, IL-6, IL-18 secretion causing cytokine storms. The translation of the knowledge on how the resulting systemic inflammation can lead to life-threatening complications into novel treatments and vaccine technologies is underway. Nevertheless, previously existing knowledge on the role of cytoplasmatic or circulating self-DNA as a pro-inflammatory damage-associated molecular pattern (DAMP) was largely ignored. Pathologies reported ‘de novo’ for patients infected with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 to be outcomes of self-DNA-driven inflammation in fact had been linked earlier to self-DNA in different contexts, e.g., the infection with Human Immunodeficiency Virus (HIV)-1, sterile inflammation, and autoimmune diseases. I highlight particularly how synergies with other DAMPs can render immunogenic properties to normally non-immunogenic extracellular self-DNA, and I discuss the shared features of the gp41 unit of the HIV-1 envelope protein and the SARS-CoV 2 Spike protein that enable HIV-1 and SARS-CoV-2 to interact with cell or nuclear membranes, trigger syncytia formation, inflict damage to their host’s DNA, and trigger inflammation – likely for their own benefit. These similarities motivate speculations that similar mechanisms to those driven by gp41 can explain how inflammatory self-DNA contributes to some of most frequent adverse events after vaccination with the BNT162b2 mRNA (Pfizer/BioNTech) or the mRNA-1273 (Moderna) vaccine, i.e., myocarditis, herpes zoster, rheumatoid arthritis, autoimmune nephritis or hepatitis, new-onset systemic lupus erythematosus, and flare-ups of psoriasis or lupus. The hope is to motivate a wider application of the lessons learned from the experiences with COVID-19 and the new mRNA vaccines to combat future non-COVID-19 diseases.

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“…The possibility of evaluating the effect of vaccination against COVID-19 and post-COVID-19 complications was studied using methylation-based cfDNA biomarkers. cfDNA released from dying immune cells to blood after SARS-CoV-2 vaccination have been studied by Fox-Fisher et al [ 217 ]. The primary vaccination caused elevated levels of B-cell cfDNA, which correlates with memory B-cells and neutralizing antibodies against SARS-CoV-2, both measured after the booster.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

The Diagnostic, Prognostic, and Therapeutic Potential of Cell-Free DNA with a Special Focus on COVID-19 and Other Viral Infections

Hovhannisyan,

Harutyunyan,

Aroutiounian

et al. 2023

IJMS

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Cell-free DNA (cfDNA) in human blood serum, urine, and other body fluids recently became a commonly used diagnostic marker associated with various pathologies. This is because cfDNA enables a much higher sensitivity than standard biochemical parameters. The presence of and/or increased level of cfDNA has been reported for various diseases, including viral infections, including COVID-19. Here, we review cfDNA in general, how it has been identified, where it can derive from, its molecular features, and mechanisms of release and clearance. General suitability of cfDNA for diagnostic questions, possible shortcomings and future directions are discussed, with a special focus on coronavirus infection.

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B cell-derived cfDNA after primary BNT162b2 mRNA vaccination anticipates memory B cells and SARS-CoV-2 neutralizing antibodies

Cited by 6 publications

References 41 publications

Long-Term Risk of Autoimmune Diseases After mRNA-based COVID-19 Vaccination: A Korean Population-based Nationwide Cohort Study

Long-Term Risk of Autoimmune Diseases After mRNA-based COVID-19 Vaccination: A Korean Population-based Nationwide Cohort Study

Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies

The Diagnostic, Prognostic, and Therapeutic Potential of Cell-Free DNA with a Special Focus on COVID-19 and Other Viral Infections

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