ARE WE STARTING TO SEE A.D.E.? Supporting source #1:

Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus
Chien-Te Tseng,Elena Sbrana,Naoko Iwata-Yoshikawa,Patrick C. Newman,Tania Garron,Robert L. Atmar,Clarence J. Peters,Robert B. Couch
Published: April 20, 2012

Results
All vaccines induced serum neutralizing antibody with increasing dosages and/or alum significantly increasing responses. Significant reductions of SARS-CoV two days after challenge was seen for all vaccines and prior live SARS-CoV. All mice exhibited histopathologic changes in lungs two days after challenge including all animals vaccinated (Balb/C and C57BL/6) or given live virus, influenza vaccine, or PBS suggesting infection occurred in all. Histopathology seen in animals given one of the SARS-CoV vaccines was uniformly a Th2-type immunopathology with prominent eosinophil infiltration, confirmed with special eosinophil stains. The pathologic changes seen in all control groups lacked the eosinophil prominence.

Conclusions
These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035421

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ARE WE STARTING TO SEE A.D.E.? Supporting source #2:

Informed consent disclosure to vaccine trial subjects of risk of COVID‐19 vaccines worsening clinical disease
Timothy Cardozo and Ronald Veazey

Results of the study
COVID‐19 vaccines designed to elicit neutralising antibodies may sensitise vaccine recipients to more severe disease than if they were not vaccinated. Vaccines for SARS, MERS and RSV have never been approved, and the data generated in the development and testing of these vaccines suggest a serious mechanistic concern: that vaccines designed empirically using the traditional approach (consisting of the unmodified or minimally modified coronavirus viral spike to elicit neutralising antibodies), be they composed of protein, viral vector, DNA or RNA and irrespective of delivery method, may worsen COVID‐19 disease via antibody‐dependent enhancement (ADE). This risk is sufficiently obscured in clinical trial protocols and consent forms for ongoing COVID‐19 vaccine trials that adequate patient comprehension of this risk is unlikely to occur, obviating truly informed consent by subjects in these trials.

Conclusions drawn from the study and clinical implications
The specific and significant COVID‐19 risk of ADE should have been and should be prominently and independently disclosed to research subjects currently in vaccine trials, as well as those being recruited for the trials and future patients after vaccine approval, in order to meet the medical ethics standard of patient comprehension for informed consent.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645850/

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ARE WE STARTING TO SEE A.D.E.? Supporting source #3:

Pfizer says immunity can drop to 83% within four months in people who got its COVID-19 shot, further bolstering the company case for a booster
Last Updated: Aug. 5, 2021

The effectiveness of Pfizer’s COVID-19 shot can drop to 83.7% within four to six months after getting the second dose of its vaccine. This is the latest indication that vaccine-induced immunity to the virus can wane and some kind of boost may be necessary in the future.

New research published Wednesday as a preprint indicates that the Pfizer Inc. PFE, +0.34% shot provides 96.2% protection for the first two months, 90.1% effectiveness between the second and fourth months, and 83.7% of protection for the fourth, fifth, and six months.

“We will need a booster eight to 12 months from the second dose,” Pfizer CEO Albert Bourla said Wednesday, according to a FactSet transcript of the company’s second-quarter earnings call.

The drug maker has been making the case for booster shots, citing limited data from its own clinical research and real-world data out of Israel, where Pfizer’s vaccine is the predominant shot in circulation....

www.marketwatch.com/story/pfizer-says-immunity-drops-to-83-within-six-months-in-people-who-got-its-covid-19-shot-further-bolstering-the-company-case-for-a-booster-11627579817

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ARE WE STARTING TO SEE A.D.E.? Supporting source #4:

Infection-enhancing anti-SARS-CoV-2 antibodies recognize both the original Wuhan/D614G strain and Delta variants. A potential risk for mass vaccination?
Nouara Yahi, Henri Chahinian, Jacques Fantini

Abstract
Antibody dependent enhancement (ADE) of infection is a safety concern for vaccine strategies. In a recent publication, Li et al. (Cell 184 :4203-4219, 2021) have reported that infection-enhancing antibodies directed against the N-terminal domain (NTD) of the SARS-CoV-2 spike protein facilitate virus infection in vitro, but not in vivo. However, this study was performed with the original Wuhan/D614G strain. Since the Covid-19 pandemic is now dominated with Delta variants, we analyzed the interaction of facilitating antibodies with the NTD of these variants. Using molecular modeling approaches, we show that enhancing antibodies have a higher affinity for Delta variants than for Wuhan/D614G NTDs. We show that enhancing antibodies reinforce the binding of the spike trimer to the host cell membrane by clamping the NTD to lipid raft microdomains. This stabilizing mechanism may facilitate the conformational change that induces the demasking of the receptor binding domain. As the NTD is also targeted by neutralizing antibodies, our data suggest that the balance between neutralizing and facilitating antibodies in vaccinated individuals is in favor of neutralization for the original Wuhan/D614G strain. However, in the case of the Delta variant, neutralizing antibodies have a decreased affinity for the spike protein, whereas facilitating antibodies display a strikingly increased affinity. Thus, ADE may be a concern for people receiving vaccines based on the original Wuhan strain spike sequence (either mRNA or viral vectors). Under these circumstances, second generation vaccines with spike protein formulations lacking structurally-conserved ADE-related epitopes should be considered.

https://pubmed.ncbi.nlm.nih.gov/34384810/

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ARE WE STARTING TO SEE A.D.E.? Supporting source #5:

UK scientists back Covid boosters as study finds post-jab falls in antibodies
Exclusive: Waning antibody levels are possible warning sign of lower protection in months after vaccination

The UCL Virus Watch study found that antibodies generated by two doses of the Oxford/AstraZeneca and Pfizer/BioNTech vaccines started to wane as early as six weeks after the second shot, in some cases falling more than 50% over 10 weeks.

https://www.theguardian.com/world/2021/jul/22/uk-scientists-back-covid-boosters-as-study-finds-post-jab-falls-in-antibodies

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ARE WE STARTING TO SEE A.D.E.? Supporting source #6:

Israel says Pfizer Covid vaccine is just 39% effective as delta spreads, but still prevents severe illness
JUL 23 2021

https://www.cnbc.com/2021/07/23/delta-variant-pfizer-covid-vaccine-39percent-effective-in-israel-prevents-severe-illness.html

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ARE WE STARTING TO SEE A.D.E.? Supporting source #7:

Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections
Sivan Gazit, Roei Shlezinger, Galit Perez, Roni Lotan, Asaf Peretz, Amir Ben-Tov, Dani Cohen, Khitam Muhsen, Gabriel Chodick, Tal Patalon

Results
SARS-CoV-2-naïve vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naïve vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected.

https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v1.full

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ARE WE STARTING TO SEE A.D.E.? Supporting source #8:

The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood–brain barrier
Tetyana P. Buzhdygan, Brandon J. DeOre, Abigail Baldwin-Leclair, Trent A. Bullock, Hannah M. McGary, Jana A. Khan, Roshanak Razmpour, Jonathan F. Hale, Peter A. Galie, Raghava Potula, Allison M. Andrews, and Servio H. Ramireza

Abstract
As researchers across the globe have focused their attention on understanding SARS-CoV-2, the picture that is emerging is that of a virus that has serious effects on the vasculature in multiple organ systems including the cerebral vasculature. Observed effects on the central nervous system include neurological symptoms (headache, nausea, dizziness), fatal microclot formation and in rare cases encephalitis. However, our understanding of how the virus causes these mild to severe neurological symptoms and how the cerebral vasculature is impacted remains unclear. Thus, the results presented in this report explored whether deleterious outcomes from the SARS-CoV-2 viral spike protein on primary human brain microvascular endothelial cells (hBMVECs) could be observed. The spike protein, which plays a key role in receptor recognition, is formed by the S1 subunit containing a receptor binding domain (RBD) and the S2 subunit. First, using postmortem brain tissue, we show that the angiotensin converting enzyme 2 or ACE2 (a known binding target for the SARS-CoV-2 spike protein), is ubiquitously expressed throughout various vessel calibers in the frontal cortex. Moreover, ACE2 expression was upregulated in cases of hypertension and dementia. ACE2 was also detectable in primary hBMVECs maintained under cell culture conditions. Analysis of cell viability revealed that neither the S1, S2 or a truncated form of the S1 containing only the RBD had minimal effects on hBMVEC viability within a 48 h exposure window. Introduction of spike proteins to invitro models of the blood-brain barrier (BBB) showed significant changes to barrier properties. Key to our findings is the demonstration that S1 promotes loss of barrier integrity in an advanced 3D microfluidic model of the human BBB, a platform that more closely resembles the physiological conditions at this CNS interface. Evidence provided suggests that the SARS-CoV-2 spike proteins trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function. Together, these results are the first to show the direct impact that the SARS-CoV-2 spike protein could have on brain endothelial cells; thereby offering a plausible explanation for the neurological consequences seen in COVID-19 patients.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547916/

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ARE WE STARTING TO SEE A.D.E.? Supporting source #9:

SARS-CoV-2 spike proteins disrupt the blood-brain barrier, new research shows
Potentially raising risk of neurological damage in COVID-19 patients
Date: October 29, 2020

The researchers then investigated the effects of the SARS-CoV-2 spike protein on brain endothelial cells in cell culture models. Introduction of the spike protein, particularly a portion designated subunit 1, produced substantial changes in endothelial barrier function that led to declines in barrier integrity. The researchers also uncovered evidence that subunit 2 of the SARS-CoV-2 spike protein can directly impact blood-brain barrier function. "This is of importance because unlike subunit 1, subunit 2 of the spike protein doesn't bind to ACE2, meaning that a breach to the blood-brain barrier could occur in a manner that is independent of ACE2," explained postdoctoral fellow and first author on the new report Tetyana P. Buzhdygan, PhD.

https://www.sciencedaily.com/releases/2020/10/201029141941.htm

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ARE WE STARTING TO SEE A.D.E.? Supporting source #10 of 10—final in the series:

Intravenous injection of COVID-19 mRNA vaccine can induce acute myopericarditis in mouse model
Can Li, Yanxia Chen, Yan Zhao, David Christopher Lung, Zhanhong Ye, Wenchen Song, Fei-Fei Liu, Jian-Piao Cai, Wan-Man Wong, Cyril Chik-Yan Yip....

Post-vaccination myopericarditis is reported after immunization with COVID-19 mRNA-vaccines. The effect of accidental intravenous injection of this vaccine on the heart is unknown.

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab707/6353927

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