The impact of BNT162b2 mRNA vaccine on adaptive and innate immune responses

Föhse, Konstantin; Geckin, Büsra; Zoodsma, Martijn; Kılıç, Gizem; Liu, Zhaoli; Röring, Rutger J.; Overheul, Gijs J.; Maat, Josephine S. van de; Bulut, Özlem; Hoogerwerf, Jacobien J.; Oever, Jaap ten; Simonetti, Elles; Schaal, Heiner; Adams, Ortwin; Müller, Lisa; Ostermann, Philipp Niklas; Veerdonk, Frank L. van de; Joosten, Leo A. B.; Haagmans, Bart L.; Crevel, Reinout van; Rij, Ronald P. van; GeurtsvanKessel, Corine; Jonge, Marien I. de; Li, Yang; Domínguez‐Andrés, Jorge; Netea, Mihai G.

doi:10.1101/2021.05.03.21256520

Cited by 15 publications

(10 citation statements)

References 83 publications

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“…Local, such as so-called Covid arm [ 47 ], and distal inflammatory reactions in the heart and brain have been reported with the mRNA-LNP platform [ 48 – 53 ]. The robust inflammation driven by the ionizable lipid component of the LNPs [ 7 ] likely contributed to the innate and adaptive immune reprogramming recently reported with this vaccine platform [ 54 ]. Thus, we think that more basic and translational research would be needed before this platform gets full approval for human use.…”

Section: Discussionmentioning

confidence: 99%

Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 immune responses

et al. 2022

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Nucleoside modified mRNA combined with Acuitas Therapeutics’ lipid nanoparticles (LNPs) has been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs’ ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper (Tfh) cells and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, these mice remained protected from lethal influenza and SARS-CoV-2 challenges. We further found that IL-6, unlike neutrophils, was required to generate normal Tfh cells and antibody responses, but not for protection from influenza challenge. In summary, here we bring evidence that the mRNA-LNP platform can support the induction of protective immune responses in the absence of certain innate immune cells and cytokines.

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Section: Discussionmentioning

confidence: 99%

Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 immune responses

et al. 2022

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“…Second, the small probability will have no meaning if we consider multiple factor life model. In Based on sistent with the finding that Pfizer mRNA vaccine actually diminishes innate immunity [255].…”

Section: Deaths Without Any Cluementioning

confidence: 99%

FDA Should Re-evaluate All mRNA Vaccines and Revoke Their Use Authorizations (The Short Version).

Wu¹

2022

IJCV

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Drug industry, controlling medical publishers and large media promote flawed medicine for their revenues by systematically laundering medical knowledge in decades. They maintain and promote flawed research models and suppress disruptive discoveries, thereby precluding reform of medicine. In this study, I will deeply explore how the wrong life model, population-based research model, misused clinical trials, flawed statistical models, the symptom based research methods, binary disease classification, failure to address the massive vital organ capacities, failure to correct biases caused by expected delay in realizing side effects, and failure to address the interference effects of non-controllable factors affect the conclusions of “effectiveness and safety” for mRNA vaccines. I will directly analyze three studies that have been relied upon by FDA in approving mNRA use authorizations: one BNT162b2 effectiveness study published in NEJM, one booster shot study published in NEJM and a Seven Integrated Health Care Organizations study published by CDC. I will expose fatal flaws in the frequency risk concept, effectiveness rate, and hazard reduction ratios, and show why 3% death rate, 95% effectiveness rate and 90% mortality reduction are all meaningless and misleading, and should never have been used as treatment guidance. I will also examine common biases that can be easily practiced by sponsors’ researchers to alter conclusions in favor of approval. By relying on laundered medical “knowledge”, FDA has consistently failed to predict latent drug side effects for any drugs and vaccines in its history. FDA approved disastrous DES in 1941, Swine Flu vaccine in 1976, and mRNA vaccines in 2020. The vaccines are used to deliver short-term benefits on a small percent of persons at the costs of damaging health, causing deaths that could be avoided, and shortening lifespans for all people in the population. I thus urge FDA to reevaluate all mRNA vaccines and revoke their use authorizations.

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“…Immune receptor TLR3,7,8 and RIG-1 are intimately involved in targeting such secondary structures and their response is RNA modification dependent 19 . This has been described as "reprogramming the innate immune and adaptive immune response" 20 . This may explain the increased rate of Herpes Zoster, HHV6/HHV7 (Pityriasis rosea) and Epstein-Barr reactivation post mRNA vaccination [21][22][23][24][25][26] .…”

Section: Fidelity Of Spike Protein Expressionmentioning

confidence: 99%

“…There is limited literature describing fidelity of mRNA vaccine derived spike protein expression. The best in-vivo evidence of heterogeneous translation of vaccine derived spike protein is from Figure 2C While these truncated or elongated promiscuous translation products may be rare events, this does bring to focus the question of dosage and spike protein duration with mRNA vaccines that ablate many components of the innate immune system 20 .…”

Section: Limited Evidence Of Pure Vaccine Derived Spike Protein Expression In Humansmentioning

confidence: 99%

Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease

McKernan¹

2021

Preprint

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Codon optimization describes the process used to increase protein production by use of alternative but synonymous codon changes. In SARS-CoV-2 mRNA vaccines codon optimizations can result in differential secondary conformations that inevitably affect a protein’s function with significant consequences to the cell. Importantly, when codon optimization increases the GC content of synthetic mRNAs, there can be an inevitable enrichment of G-quartets which potentially form G-quadruplex structures. The emerging G-quadruplexes are favorable binding sites of RNA binding proteins like helicases that inevitably affect epigenetic reprogramming of the cell by altering transcription, translation and replication. In this study, we performed a RNAfold analysis to investigate alterations in secondary structures of mRNAs in SARS-CoV-2 vaccines due to codon optimization. We show a significant increase in the GC content of mRNAs in vaccines as compared to native SARS-CoV-2 RNA sequences encoding the spike protein. As the GC enrichment leads to more G-quadruplex structure formations, these may contribute to potential pathological processes initiated by SARS-CoV-2 molecular vaccination.

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The impact of BNT162b2 mRNA vaccine on adaptive and innate immune responses

Cited by 15 publications

References 83 publications

Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 immune responses

Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 immune responses

FDA Should Re-evaluate All mRNA Vaccines and Revoke Their Use Authorizations (The Short Version).

Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease

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