All of you Jacklegs screaming about COVID
- Thread starter Skulnik
- Start date
-
- Tags
- bullshit kulnik is a fag
- Status
Trumka- dead of heart attack
The head of the AFL-CIO said on Tuesday that the labor organization supports vaccine mandates for workers.
AFL-CIO President Richard Trumka outlined the group's position during an interview on C-SPAN's "The Washington Journal," explaining why such mandates are important.
"Yes we do," Trumka said, when asked if the AFL-CIO supports vaccine mandates. "If you are coming back into the workplace, you have to know what's around you."
After we get everybody vaccinated in the United States, we have to help people around the world get vaccinated
[link to thehill.com (secure)]
https://thehill.com/business-a-lobb...l-cio-backing-vaccine-requirement-for-workers
The head of the AFL-CIO said on Tuesday that the labor organization supports vaccine mandates for workers.
AFL-CIO President Richard Trumka outlined the group's position during an interview on C-SPAN's "The Washington Journal," explaining why such mandates are important.
"Yes we do," Trumka said, when asked if the AFL-CIO supports vaccine mandates. "If you are coming back into the workplace, you have to know what's around you."
After we get everybody vaccinated in the United States, we have to help people around the world get vaccinated
[link to thehill.com (secure)]
https://thehill.com/business-a-lobb...l-cio-backing-vaccine-requirement-for-workers
It doesn't change the fact that ALL 3 sources I provided are listed as "High Credibility". Like I said, thanks for trying. :0008
Journal ListWiley-Blackwell Online OpenPMC7645850
Logo of blackwellopen
International Journal of Clinical Practice
Int J Clin Pract. 2021 Mar; 75(3): e13795.
Published online 2020 Dec 4. doi: 10.1111/ijcp.13795
PMCID: PMC7645850
PMID: 33113270
Informed consent disclosure to vaccine trial subjects of risk of COVID‐19 vaccines worsening clinical disease
Timothy Cardozocorresponding author 1 and Ronald Veazey 2
Author information Copyright and License information Disclaimer
This article has been cited by other articles in PMC.
Associated Data
Data Availability Statement
Go to:
Abstract
Aims of the study
Patient comprehension is a critical part of meeting medical ethics standards of informed consent in study designs. The aim of the study was to determine if sufficient literature exists to require clinicians to disclose the specific risk that COVID‐19 vaccines could worsen disease upon exposure to challenge or circulating virus.
Methods used to conduct the study
Published literature was reviewed to identify preclinical and clinical evidence that COVID‐19 vaccines could worsen disease upon exposure to challenge or circulating virus. Clinical trial protocols for COVID‐19 vaccines were reviewed to determine if risks were properly disclosed.
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.
Go to:
1. THE RISK OF ADE IN COVID‐19 VACCINES IS NON‐THEORETICAL AND COMPELLING
Vaccine‐elicited enhancement of disease was previously observed in human subjects with vaccines for respiratory syncytial virus (RSV), dengue virus and measles. 1 Vaccine‐elicited enhancement of disease was also observed with the SARS and MERS viruses and with feline coronavirus, which are closely related to SARS‐CoV‐2, the causative pathogen of COVID‐19 disease. The immune mechanisms of this enhancement have invariably involved antibodies, from direct antibody‐dependent enhancement, to immune complex formation by antibodies, albeit accompanied by various coordinated cellular responses, such as Th2 T‐cell skewing. 2 , 3 , 4 , 5 , 6 , 7 Notably, both neutralising and non‐neutralising antibodies have been implicated. A recent study revealed IgG‐mediated acute lung injury in vivo in macaques infected with SARS that correlated with a vaccine‐elicited, neutralising antibody response. 8 Inflammation and tissue damage in the lung in this animal model recapitulated the inflammation and tissue damage in the lungs of SARS‐infected patients who succumbed to the disease. The time course was also similar, with the worst damage occurring in delayed fashion in synchrony with ramping up of the immune response. Remarkably, neutralising antibodies controlled the virus in the animal, but then would precipitate a severe, tissue‐damaging, inflammatory response in the lung. This is a similar profile to immune complex‐mediated disease seen with RSV vaccines in the past, wherein vaccinees succumbed to fatal enhanced RSV disease because of the formation of antibody‐virus immune complexes that precipitated harmful, inflammatory immune responses. It is also similar to the clinical course of COVID‐19 patients, in whom severe COVID‐19 disease is associated with the development of anti‐SARS‐CoV‐2 serum antibodies, 9 with titres correlating directly with the severity of disease. 10 Conversely, subjects who recover quickly may have low or no anti‐SARS‐CoV‐2 serum antibodies. 11
The elicitation of antibodies, specifically neutralising antibodies, is the goal of nearly every current SARS‐CoV‐2 vaccine candidate. The prior evidence that vaccine‐elicited, antibody‐dependent enhancement (ADE) of disease is likely to occur to some degree with COVID‐19 vaccines is vertically consistent from controlled SARS studies in primates to clinical observations in SARS and COVID‐19. Thus, a finite, non‐theoretical risk is evident in the medical literature that vaccine candidates composed of the SARS‐CoV‐2 viral spike and eliciting anti‐SARS‐CoV‐2 antibodies, be they neutralising or not, place vaccinees at higher risk for more severe COVID‐19 disease when they encounter circulating viruses. Indeed, studies in mice of prior SARS vaccines revealed this exact phenotype, with four human vaccine candidates eliciting neutralising antibodies and protecting against SARS challenge, but viral re‐challenge of thus vaccinated animals resulting in immunopathologic lung disease. 5 Independently, SARS/MERS vaccine candidates, commonly exhibited ADE associated with high inflammatory morbidity in preclinical models, obstructing their advancement to the clinic. 4 , 12 SARS ADE of both disease in non‐human primates and viral infection of cells in vitro was clearly mapped to specific antibody‐targeted SARS viral spike epitopes. 6 This phenomenon was consistent across a variety of vaccine platforms, including DNA, vector primes and virus‐like particles (VLP), irrespective of inoculation method (oral, intramuscular, subcutaneous, etc). An unknown variable is how long this tissue damage lasts, possibly resulting in permanent morbidity (eg, diabetes from pancreatic damage 7 ).
Current data on COVID‐19 vaccines is limited, but does not so far reveal evidence of ADE of disease. Non‐human primate studies of Moderna's mRNA‐1273 vaccine showed excellent protection, with no detectable immunopathology. 13 Phase 1 trials of several vaccines have not reported any immunopathology in subjects administered the candidate vaccines. However, these subjects were unlikely to have yet encountered circulating virus. 14 Nevertheless, all preclinical studies to date have been performed with the Wuhan or closely related strains of the virus, while a mutant D614G virus is now the most prevalent circulating form. Several observations suggest that this alternative form may be antigenically distinct from the Wuhan derived strain, not so much in composition, but in conformation of the viral spike and exposure of neutralisation epitopes. 15 , 16 , 17 , 18 Similarly, Phase 1 and 2 clinical trials of vaccine candidates have only been designed around immunogenicity as an efficacy end point and have not been designed to capture exposure of subjects to circulating virus after vaccination, which is when ADE/immunopathology is designed to occur. Thus, the absence of ADE evidence in COVID‐19 vaccine data so far does not absolve investigators from disclosing the risk of enhanced disease to vaccine trial participants, and it remains a realistic, non‐theoretical risk to the subjects.
Go to:
2. CHALLENGES TO INFORMED CONSENT FOR COVID‐19 VACCINE STUDIES
Informed consent procedures for vaccine trials commonly include disclosure of very minor risks such as injection site reactions, rare risks from past, unrelated vaccines/viruses, such as Guillain‐Barre syndrome for swine flu (interest in which is likely behind the interest in Astra Zeneca's recent vaccine transverse myelitis event) and generic statements about the risk of idiosyncratic systemic adverse events and death. Specific risks to research participants derived from biological mechanism are rarely included, often because of ambiguity about their applicability. 19
Signed consent forms from the COVID‐19 vaccine trials are not publicly available because of privacy concerns. They also vary from clinical site to clinical site, and sample consent forms on which they are based are not required to be disclosed until after the trial is over, if at all. However, these consent forms are usually very similar in content to the ?Risks to participants? section of the trial protocols, which have been released publicly by Pfizer, Moderna and Johnson & Johnson for their COVID‐19 vaccine trials ( 20 & Supplement). As these three vaccines are representative of the diversity of vaccines being tested, it is very likely that the consent form inferred from these protocols is similar or identical to those from any and all of the vaccine trials currently underway. All three protocols mention the risk of disease enhancement by the vaccine, but all three list this risk last or next to last in the list of risks, after risks from the Ad26‐Cov2 vector, adenovirus vectors in general, risks of vaccination in general, risks for pregnancy and birth control (which are said to be ?unknown?), risks of blood draws and risks from collection of nasal swab samples (for the Johnson and Johnson vaccine), after allergy, fainting, local site injection reaction, general systemic adverse reactions and laboratory abnormalities for the Moderna vaccine and after local site injection reactions and general systemic adverse events for the Pfizer vaccine. In addition, both Moderna and Johnson and Johnson term the risk of vaccine‐elicited disease enhancement as ?theoretical.? Finally, in citing the risk, Pfizer and Moderna note prior evidence of vaccine‐elicited disease enhancement with RSV and dengue, as well as feline coronavirus (Pfizer) and measles (Moderna), however, SARS and MERS are not mentioned. Johnson and Johnson discusses SARS and MERS, but make an unusual scientific argument that vaccine‐elicited disease enhancement is because of non‐neutralising antibodies and Th2‐skewed cellular responses and that Ad26 vaccination does not exhibit this profile.Blank consent forms for AstraZeneca and Johnson and Johnson are also available online at https://restoringtrials.org/2020/09/18/covid19trialprotocolandstudydocs/, and while the AstraZeneca form clearly discloses the specific risk of ADE, the disclosure is listed last among risks only in an attached information sheet. In all, the evidence from the Pfizer, Moderna and Johnson & Johnson protocols for their COVID‐19 vaccine trials and the sample consent forms, when contrasted with the evidence for antibody‐dependent enhancement of disease presented by this report and widely available to any skilled practitioner in the field, establishes that patient comprehension of the specific risk that receiving the COVID‐19 vaccine could convert a subject from someone who experiences mild disease to someone who experiences severe disease, lasting morbidity or even death is unlikely to be achieved by the informed consent procedures planned for these clinical trials.
Medical ethics standards required that, given the extent of evidence in the medical literature reviewed above, the risk of ADE should be clearly and emphatically distinguished in the informed consent from risks observed rarely as well as the more obvious risk of lack of efficacy, which is unrelated to the specific risk of ADE. Based on the published literature, it should have been obvious to any skilled medical practitioner in 2019 that there is a significant risk to vaccine research subjects that they may experience severe disease once vaccinated, while they might only have experienced a mild, self‐limited disease if not vaccinated. The consent should also clearly distinguish the specific risk of worsened COVID‐19 disease from generic statements about risk of death and generic risk of lack of efficacy of the vaccine.
Go to:
3. CONCLUSION
Given the strong evidence that ADE is a non‐theoretical and compelling risk for COVID‐19 vaccines and the ?laundry list? nature of informed consents, disclosure of the specific risk of worsened COVID‐19 disease from vaccination calls for a specific, separate, informed consent form and demonstration of patient comprehension in order to meet medical ethics standards. The informed consent process for ongoing COVID‐19 vaccine trials does not appear to meet this standard. While the COVID‐19 global health emergency justifies accelerated vaccine trials of candidates with known liabilities, such an acceleration is not inconsistent with additional attention paid to heightened informed consent procedures specific to COVID‐19 vaccine risks.
Go to:
DISCLOSURE
The authors have declared no conflicts of interest for this article.
Go to:
AUTHOR CONTRIBUTIONS
TC and RV conceived this commentary. TC wrote the manuscript. RV edited and approved the manuscript.
Go to:
ACKNOWLEDGEMENTS
Supported by NIH award R21AI157604 (to TC).
Go to:
DATA AVAILABILITY STATEMENT
All data referenced in this report have been published in peer‐reviewed literature or are available on the World Wide Web/Internet at the URL?s indicated in the References section. Therefore, all data referenced in this report are publicly available in widely available data repositories.
Go to:
REFERENCES
1. Huisman W, Martina BE, Rimmelzwaan GF, Gruters RA, Osterhaus AD. Vaccine‐induced enhancement of viral infections. Vaccine. 2009;27:505‐512. [PMC free article] [PubMed] [Google Scholar]
2. Boyoglu‐Barnum S, Chirkova T, Anderson LJ. Biology of infection and disease pathogenesis to guide RSV vaccine development. Front Immunol. 2019;10:1675. [PMC free article] [PubMed] [Google Scholar]
3. Chen WH, Hotez PJ, Bottazzi ME. Potential for developing a SARS‐CoV receptor‐binding domain (RBD) recombinant protein as a heterologous human vaccine against coronavirus infectious disease (COVID)‐19. Human Vacc Immunother. 2020;16:1239‐1242. [PMC free article] [PubMed] [Google Scholar]
4. Jiang S, He Y, Liu S. SARS vaccine development. Emerg Infect Dis. 2005;11:1016‐1020. [PMC free article] [PubMed] [Google Scholar]
5. Tseng CT, Sbrana E, Iwata‐Yoshikawa N, et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One. 2012;7:e35421. [PMC free article] [PubMed] [Google Scholar]
6. Wang Q, Zhang L, Kuwahara K, et al. Immunodominant SARS coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in non‐human primates. ACS Infect Dis. 2016;2:361‐376. [PMC free article] [PubMed] [Google Scholar]
7. Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010;47:193‐199. [PMC free article] [PubMed] [Google Scholar]
8. Liu L, Wei Q, Lin Q, et al. Anti‐spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS‐CoV infection. JCI insight. 2019;4:e123158. [PMC free article] [PubMed] [Google Scholar]
9. Liu ZL, Liu Y, Wan LG, et al. Antibody profiles in mild and severe cases of COVID‐19. Clin Chem. 2020;66:1102?1104. [PMC free article] [PubMed] [Google Scholar]
10. Piccoli L, Park YJ, Tortorici MA, et al. Mapping neutralizing and immunodominant sites on the SARS‐CoV‐2 spike receptor‐binding domain by structure‐guided high‐resolution serology. Cell. 2020;S0092‐8674:31234‐4 [PMC free article] [PubMed] [Google Scholar]
11. Robbiani DF, Gaebler C, Muecksch F, et al. Convergent antibody responses to SARS‐CoV‐2 infection in convalescent individuals. bioRxiv. 2020. [PMC free article] [PubMed] [Google Scholar]
12. Yong CY, Ong HK, Yeap SK, Ho KL, Tan WS. Recent advances in the vaccine development against middle east respiratory syndrome‐coronavirus. Front Microbiol. 2019;10:1781. [PMC free article] [PubMed] [Google Scholar]
13. Corbett KS, Flynn B, Foulds KE, et al. Evaluation of the mRNA‐1273 Vaccine against SARS‐CoV‐2 in Nonhuman Primates. N Engl J Med. 2020;383:1544?1555. [PMC free article] [PubMed] [Google Scholar]
14. Mulligan MJ, Lyke KE, Kitchin N, et al. Phase 1/2 study of COVID‐19 RNA vaccine BNT162b1 in adults. Nature. 2020;586:589?593. [PubMed] [Google Scholar]
15. Becerra‐Flores M, Cardozo T. SARS‐CoV‐2 viral spike G614 mutation exhibits higher case fatality rate. Int J Clin Pract. 2020;74:e13525. [PMC free article] [PubMed] [Google Scholar]
16. Korber B, Fischer WM, Gnanakaran S, et al. Tracking changes in SARS‐CoV‐2 spike: evidence that D614G increases infectivity of the COVID‐19 virus. Cell. 2020;182:812‐827.e819. [PMC free article] [PubMed] [Google Scholar]
17. Mansbach RA, Chakraborty S, Nguyen K, Montefiori D, Korber B, Gnanakaran S. The SARS‐CoV‐2 spike variant D614G favors an open conformational state. bioRxiv. 2020. [PMC free article] [PubMed] [Google Scholar]
18. Zhang L, Jackson C, Mou H, et al. The D614G mutation in the SARS‐CoV‐2 spike protein reduces S1 shedding and increases infectivity. bioRxiv. 2020. [Google Scholar]
19. Wendler D. What should be disclosed to research participants? Am J Bioeth. 2013;13:3‐8. [PMC free article] [PubMed] [Google Scholar]
20. McNamara D.Three Major COVID Vaccine Developers Release Detailed Trial Protocols. https://wwwmedscapecom/viewarticle/937845; 2020.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645850/
Logo of blackwellopen
International Journal of Clinical Practice
Int J Clin Pract. 2021 Mar; 75(3): e13795.
Published online 2020 Dec 4. doi: 10.1111/ijcp.13795
PMCID: PMC7645850
PMID: 33113270
Informed consent disclosure to vaccine trial subjects of risk of COVID‐19 vaccines worsening clinical disease
Timothy Cardozocorresponding author 1 and Ronald Veazey 2
Author information Copyright and License information Disclaimer
This article has been cited by other articles in PMC.
Associated Data
Data Availability Statement
Go to:
Abstract
Aims of the study
Patient comprehension is a critical part of meeting medical ethics standards of informed consent in study designs. The aim of the study was to determine if sufficient literature exists to require clinicians to disclose the specific risk that COVID‐19 vaccines could worsen disease upon exposure to challenge or circulating virus.
Methods used to conduct the study
Published literature was reviewed to identify preclinical and clinical evidence that COVID‐19 vaccines could worsen disease upon exposure to challenge or circulating virus. Clinical trial protocols for COVID‐19 vaccines were reviewed to determine if risks were properly disclosed.
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.
Go to:
1. THE RISK OF ADE IN COVID‐19 VACCINES IS NON‐THEORETICAL AND COMPELLING
Vaccine‐elicited enhancement of disease was previously observed in human subjects with vaccines for respiratory syncytial virus (RSV), dengue virus and measles. 1 Vaccine‐elicited enhancement of disease was also observed with the SARS and MERS viruses and with feline coronavirus, which are closely related to SARS‐CoV‐2, the causative pathogen of COVID‐19 disease. The immune mechanisms of this enhancement have invariably involved antibodies, from direct antibody‐dependent enhancement, to immune complex formation by antibodies, albeit accompanied by various coordinated cellular responses, such as Th2 T‐cell skewing. 2 , 3 , 4 , 5 , 6 , 7 Notably, both neutralising and non‐neutralising antibodies have been implicated. A recent study revealed IgG‐mediated acute lung injury in vivo in macaques infected with SARS that correlated with a vaccine‐elicited, neutralising antibody response. 8 Inflammation and tissue damage in the lung in this animal model recapitulated the inflammation and tissue damage in the lungs of SARS‐infected patients who succumbed to the disease. The time course was also similar, with the worst damage occurring in delayed fashion in synchrony with ramping up of the immune response. Remarkably, neutralising antibodies controlled the virus in the animal, but then would precipitate a severe, tissue‐damaging, inflammatory response in the lung. This is a similar profile to immune complex‐mediated disease seen with RSV vaccines in the past, wherein vaccinees succumbed to fatal enhanced RSV disease because of the formation of antibody‐virus immune complexes that precipitated harmful, inflammatory immune responses. It is also similar to the clinical course of COVID‐19 patients, in whom severe COVID‐19 disease is associated with the development of anti‐SARS‐CoV‐2 serum antibodies, 9 with titres correlating directly with the severity of disease. 10 Conversely, subjects who recover quickly may have low or no anti‐SARS‐CoV‐2 serum antibodies. 11
The elicitation of antibodies, specifically neutralising antibodies, is the goal of nearly every current SARS‐CoV‐2 vaccine candidate. The prior evidence that vaccine‐elicited, antibody‐dependent enhancement (ADE) of disease is likely to occur to some degree with COVID‐19 vaccines is vertically consistent from controlled SARS studies in primates to clinical observations in SARS and COVID‐19. Thus, a finite, non‐theoretical risk is evident in the medical literature that vaccine candidates composed of the SARS‐CoV‐2 viral spike and eliciting anti‐SARS‐CoV‐2 antibodies, be they neutralising or not, place vaccinees at higher risk for more severe COVID‐19 disease when they encounter circulating viruses. Indeed, studies in mice of prior SARS vaccines revealed this exact phenotype, with four human vaccine candidates eliciting neutralising antibodies and protecting against SARS challenge, but viral re‐challenge of thus vaccinated animals resulting in immunopathologic lung disease. 5 Independently, SARS/MERS vaccine candidates, commonly exhibited ADE associated with high inflammatory morbidity in preclinical models, obstructing their advancement to the clinic. 4 , 12 SARS ADE of both disease in non‐human primates and viral infection of cells in vitro was clearly mapped to specific antibody‐targeted SARS viral spike epitopes. 6 This phenomenon was consistent across a variety of vaccine platforms, including DNA, vector primes and virus‐like particles (VLP), irrespective of inoculation method (oral, intramuscular, subcutaneous, etc). An unknown variable is how long this tissue damage lasts, possibly resulting in permanent morbidity (eg, diabetes from pancreatic damage 7 ).
Current data on COVID‐19 vaccines is limited, but does not so far reveal evidence of ADE of disease. Non‐human primate studies of Moderna's mRNA‐1273 vaccine showed excellent protection, with no detectable immunopathology. 13 Phase 1 trials of several vaccines have not reported any immunopathology in subjects administered the candidate vaccines. However, these subjects were unlikely to have yet encountered circulating virus. 14 Nevertheless, all preclinical studies to date have been performed with the Wuhan or closely related strains of the virus, while a mutant D614G virus is now the most prevalent circulating form. Several observations suggest that this alternative form may be antigenically distinct from the Wuhan derived strain, not so much in composition, but in conformation of the viral spike and exposure of neutralisation epitopes. 15 , 16 , 17 , 18 Similarly, Phase 1 and 2 clinical trials of vaccine candidates have only been designed around immunogenicity as an efficacy end point and have not been designed to capture exposure of subjects to circulating virus after vaccination, which is when ADE/immunopathology is designed to occur. Thus, the absence of ADE evidence in COVID‐19 vaccine data so far does not absolve investigators from disclosing the risk of enhanced disease to vaccine trial participants, and it remains a realistic, non‐theoretical risk to the subjects.
Go to:
2. CHALLENGES TO INFORMED CONSENT FOR COVID‐19 VACCINE STUDIES
Informed consent procedures for vaccine trials commonly include disclosure of very minor risks such as injection site reactions, rare risks from past, unrelated vaccines/viruses, such as Guillain‐Barre syndrome for swine flu (interest in which is likely behind the interest in Astra Zeneca's recent vaccine transverse myelitis event) and generic statements about the risk of idiosyncratic systemic adverse events and death. Specific risks to research participants derived from biological mechanism are rarely included, often because of ambiguity about their applicability. 19
Signed consent forms from the COVID‐19 vaccine trials are not publicly available because of privacy concerns. They also vary from clinical site to clinical site, and sample consent forms on which they are based are not required to be disclosed until after the trial is over, if at all. However, these consent forms are usually very similar in content to the ?Risks to participants? section of the trial protocols, which have been released publicly by Pfizer, Moderna and Johnson & Johnson for their COVID‐19 vaccine trials ( 20 & Supplement). As these three vaccines are representative of the diversity of vaccines being tested, it is very likely that the consent form inferred from these protocols is similar or identical to those from any and all of the vaccine trials currently underway. All three protocols mention the risk of disease enhancement by the vaccine, but all three list this risk last or next to last in the list of risks, after risks from the Ad26‐Cov2 vector, adenovirus vectors in general, risks of vaccination in general, risks for pregnancy and birth control (which are said to be ?unknown?), risks of blood draws and risks from collection of nasal swab samples (for the Johnson and Johnson vaccine), after allergy, fainting, local site injection reaction, general systemic adverse reactions and laboratory abnormalities for the Moderna vaccine and after local site injection reactions and general systemic adverse events for the Pfizer vaccine. In addition, both Moderna and Johnson and Johnson term the risk of vaccine‐elicited disease enhancement as ?theoretical.? Finally, in citing the risk, Pfizer and Moderna note prior evidence of vaccine‐elicited disease enhancement with RSV and dengue, as well as feline coronavirus (Pfizer) and measles (Moderna), however, SARS and MERS are not mentioned. Johnson and Johnson discusses SARS and MERS, but make an unusual scientific argument that vaccine‐elicited disease enhancement is because of non‐neutralising antibodies and Th2‐skewed cellular responses and that Ad26 vaccination does not exhibit this profile.Blank consent forms for AstraZeneca and Johnson and Johnson are also available online at https://restoringtrials.org/2020/09/18/covid19trialprotocolandstudydocs/, and while the AstraZeneca form clearly discloses the specific risk of ADE, the disclosure is listed last among risks only in an attached information sheet. In all, the evidence from the Pfizer, Moderna and Johnson & Johnson protocols for their COVID‐19 vaccine trials and the sample consent forms, when contrasted with the evidence for antibody‐dependent enhancement of disease presented by this report and widely available to any skilled practitioner in the field, establishes that patient comprehension of the specific risk that receiving the COVID‐19 vaccine could convert a subject from someone who experiences mild disease to someone who experiences severe disease, lasting morbidity or even death is unlikely to be achieved by the informed consent procedures planned for these clinical trials.
Medical ethics standards required that, given the extent of evidence in the medical literature reviewed above, the risk of ADE should be clearly and emphatically distinguished in the informed consent from risks observed rarely as well as the more obvious risk of lack of efficacy, which is unrelated to the specific risk of ADE. Based on the published literature, it should have been obvious to any skilled medical practitioner in 2019 that there is a significant risk to vaccine research subjects that they may experience severe disease once vaccinated, while they might only have experienced a mild, self‐limited disease if not vaccinated. The consent should also clearly distinguish the specific risk of worsened COVID‐19 disease from generic statements about risk of death and generic risk of lack of efficacy of the vaccine.
Go to:
3. CONCLUSION
Given the strong evidence that ADE is a non‐theoretical and compelling risk for COVID‐19 vaccines and the ?laundry list? nature of informed consents, disclosure of the specific risk of worsened COVID‐19 disease from vaccination calls for a specific, separate, informed consent form and demonstration of patient comprehension in order to meet medical ethics standards. The informed consent process for ongoing COVID‐19 vaccine trials does not appear to meet this standard. While the COVID‐19 global health emergency justifies accelerated vaccine trials of candidates with known liabilities, such an acceleration is not inconsistent with additional attention paid to heightened informed consent procedures specific to COVID‐19 vaccine risks.
Go to:
DISCLOSURE
The authors have declared no conflicts of interest for this article.
Go to:
AUTHOR CONTRIBUTIONS
TC and RV conceived this commentary. TC wrote the manuscript. RV edited and approved the manuscript.
Go to:
ACKNOWLEDGEMENTS
Supported by NIH award R21AI157604 (to TC).
Go to:
DATA AVAILABILITY STATEMENT
All data referenced in this report have been published in peer‐reviewed literature or are available on the World Wide Web/Internet at the URL?s indicated in the References section. Therefore, all data referenced in this report are publicly available in widely available data repositories.
Go to:
REFERENCES
1. Huisman W, Martina BE, Rimmelzwaan GF, Gruters RA, Osterhaus AD. Vaccine‐induced enhancement of viral infections. Vaccine. 2009;27:505‐512. [PMC free article] [PubMed] [Google Scholar]
2. Boyoglu‐Barnum S, Chirkova T, Anderson LJ. Biology of infection and disease pathogenesis to guide RSV vaccine development. Front Immunol. 2019;10:1675. [PMC free article] [PubMed] [Google Scholar]
3. Chen WH, Hotez PJ, Bottazzi ME. Potential for developing a SARS‐CoV receptor‐binding domain (RBD) recombinant protein as a heterologous human vaccine against coronavirus infectious disease (COVID)‐19. Human Vacc Immunother. 2020;16:1239‐1242. [PMC free article] [PubMed] [Google Scholar]
4. Jiang S, He Y, Liu S. SARS vaccine development. Emerg Infect Dis. 2005;11:1016‐1020. [PMC free article] [PubMed] [Google Scholar]
5. Tseng CT, Sbrana E, Iwata‐Yoshikawa N, et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One. 2012;7:e35421. [PMC free article] [PubMed] [Google Scholar]
6. Wang Q, Zhang L, Kuwahara K, et al. Immunodominant SARS coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in non‐human primates. ACS Infect Dis. 2016;2:361‐376. [PMC free article] [PubMed] [Google Scholar]
7. Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010;47:193‐199. [PMC free article] [PubMed] [Google Scholar]
8. Liu L, Wei Q, Lin Q, et al. Anti‐spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS‐CoV infection. JCI insight. 2019;4:e123158. [PMC free article] [PubMed] [Google Scholar]
9. Liu ZL, Liu Y, Wan LG, et al. Antibody profiles in mild and severe cases of COVID‐19. Clin Chem. 2020;66:1102?1104. [PMC free article] [PubMed] [Google Scholar]
10. Piccoli L, Park YJ, Tortorici MA, et al. Mapping neutralizing and immunodominant sites on the SARS‐CoV‐2 spike receptor‐binding domain by structure‐guided high‐resolution serology. Cell. 2020;S0092‐8674:31234‐4 [PMC free article] [PubMed] [Google Scholar]
11. Robbiani DF, Gaebler C, Muecksch F, et al. Convergent antibody responses to SARS‐CoV‐2 infection in convalescent individuals. bioRxiv. 2020. [PMC free article] [PubMed] [Google Scholar]
12. Yong CY, Ong HK, Yeap SK, Ho KL, Tan WS. Recent advances in the vaccine development against middle east respiratory syndrome‐coronavirus. Front Microbiol. 2019;10:1781. [PMC free article] [PubMed] [Google Scholar]
13. Corbett KS, Flynn B, Foulds KE, et al. Evaluation of the mRNA‐1273 Vaccine against SARS‐CoV‐2 in Nonhuman Primates. N Engl J Med. 2020;383:1544?1555. [PMC free article] [PubMed] [Google Scholar]
14. Mulligan MJ, Lyke KE, Kitchin N, et al. Phase 1/2 study of COVID‐19 RNA vaccine BNT162b1 in adults. Nature. 2020;586:589?593. [PubMed] [Google Scholar]
15. Becerra‐Flores M, Cardozo T. SARS‐CoV‐2 viral spike G614 mutation exhibits higher case fatality rate. Int J Clin Pract. 2020;74:e13525. [PMC free article] [PubMed] [Google Scholar]
16. Korber B, Fischer WM, Gnanakaran S, et al. Tracking changes in SARS‐CoV‐2 spike: evidence that D614G increases infectivity of the COVID‐19 virus. Cell. 2020;182:812‐827.e819. [PMC free article] [PubMed] [Google Scholar]
17. Mansbach RA, Chakraborty S, Nguyen K, Montefiori D, Korber B, Gnanakaran S. The SARS‐CoV‐2 spike variant D614G favors an open conformational state. bioRxiv. 2020. [PMC free article] [PubMed] [Google Scholar]
18. Zhang L, Jackson C, Mou H, et al. The D614G mutation in the SARS‐CoV‐2 spike protein reduces S1 shedding and increases infectivity. bioRxiv. 2020. [Google Scholar]
19. Wendler D. What should be disclosed to research participants? Am J Bioeth. 2013;13:3‐8. [PMC free article] [PubMed] [Google Scholar]
20. McNamara D.Three Major COVID Vaccine Developers Release Detailed Trial Protocols. https://wwwmedscapecom/viewarticle/937845; 2020.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645850/
COVID-19
Antibody-Dependent Enhancement
By Derek Lowe 18 December, 2020
I?ve had several questions about antibody-dependent enhancement, which has always been a worry as the coronavirus vaccines have been developed. I figured it might be worth a look at just what we know about it, why one might be worried, and why (on the other hand) one might be hopeful.
The simple definition of ADE is ?raising antibodies that don?t protect, but actually make a viral infection even worse?. And obviously, that?s the opposite of what you want. Remember that there are ?neutralizing? antibodies as opposed to non-neutralizing ones ? a neutralizing antibody, as the name implies, binds to its target in a way that shuts its function down. That?s generally done by blocking the ?business end? of a given protein target, smothering the binding surface that it would need to do its usual job. For the coronavirus, a straightforward example of a neutralizing antibody would be on that binds to the tip of the Spike protein, the receptor-binding domain (RBD) that is the part that recognizes and binds to the human ACE2 protein on a cell surface. Block that thoroughly enough, and it would seem that you have blocked the virus?s ability to infect your cells.
There are other ways, as this blog post earlier this year makes clear (or tries to!) You don?t have to just completely cap the end of the Spike protein to shut it down ? as it turns out, you can bind an antibody further down the Spike and have it be neutralizing, just so long as it interferes with the structural changes that the Spike protein needs to undergo when it starts binding to a human cell membrane. There?s a whole subunit of the Spike (S2) that is involved in the membrane-fusion step, so throwing a wrench into that will work for you, too. Proteins make all sorts of adjustments as they fit to each other: this part has to shift down and over, that bond has to rotate, and some of those adjustments may be non-negotiable (and thus targets for blocking the whole process).
So there are plenty of ways to get neutralizing antibodies, with various ways of binding to the Spike protein and in binding to other coronavirus proteins as well. But there are also plenty of ways to get non-neutralizing antibodies, ones that stick to some part of the coronavirus particle without really inconveniencing it much. That?s obviously useless, and antibody-dependent enhancement takes things down another notch, from useless to outright harmful. With ADE, the binding of such an antibody actually assists the virus, by (for example) actually making it easier for the virus to get taken up through the outer membranes of human cells. Another possibility is that an antibody that would be neutralizing if present in sufficient amounts can actually enhance infection in lower dilutions, which has been seen with influenza antibodies and other viruses as well. This seems to be through aggregation of viral particles, although other factors might be at work.
You really don?t want ADE through any of these mechanisms ? bad things happen. Dengue fever is a classic example, because it infects humans through four distinct serotypes. If you are infected with one of these and raise a successful immune response, you may well be at increased risk of serious infection with one of the other serotypes. The neutralizing antibodies for one of the types are often not neutralizing for the others, but instead allow that cell-antibody-receptor mechanism to kick in (easier infection of human monocytes), known as ?extrinsic ADE?. There?s also an ?intrinsic ADE? seen with dengue, which leads to greater viral replication inside infected monocyte cells before they burst and release their contents. The mechanisms for that are still being worked out, but seem to involve suppression of cytokine pathways.
ADE has been seen with HIV infection (where it may be mediated by one of the complement pathways, which kicks in after an antibody binds to its target), with Ebola (where a completely different complement-driven mechanism seems to be operating), with coxsackievirus (and other picornaviruses), and in many others. It should be noted that inappropriate complement activation can cause troubles of its own, which can contribute to the severity of ADE-driven disease ? this is particularly noticeable in respiratory viruses (influenza and others) and their effects in the lungs.
Evolutionarily, you?d figure that developing such things would be under positive selection pressure: higher organisms are constantly fighting off viral infections by raising antibodies to them, so something that causes this to backfire would probably be an advantage for any virus that hits on such a mechanism. So ADE is not some weirdo exception in viral infections, unfortunately ? it?s pretty widespread.
And in the same way that viral infections can involve ADE, so can the antibody responses raised by vaccines. There was an inactivated-virus vaccine tried in the 1960s against RSV (respiratory syncitial virus) that in human trials actually caused infants to come down with worse cases of RSV. This effect has been duplicated with RSV in cell cultures and in primate models, and one hypothesis has been that (as with the extrinsic-ADE of dengue), the exposed regions of the antibodies bound to the viral particles bind in turn to receptors on human cell surfaces, and allow them to be taken into the cell more directly. A 1960s inactivated measles vaccine candidate showed similar effects.
Here?s a recent paper taking all this into the context of the current pandemic. And since this post up until now has been rather gloomy, you?ll be glad to hear that the news starts to improve at this point. For one thing, the current coronavirus does not seem to productively infect macrophages, which are by far the main target for that antibody-receptor-uptake ADE mechanism. The related MERS coronavirus was able to do this, but not SARS-CoV-2, fortunately. So the two mechanisms seen in (for example) dengue do not seem to be as much of a worry. The complement-driven stuff is still on the table, though, and indeed matches up well with the ?cytokine storm? lung damage seen in severe patients.
But as that new paper says, thus far ?No definitive role for ADE in human coronavirus diseases has been established.? That may be a bit surprising, if you?ve been seeing worried stories about antibody-dependent enhancement over the last few months. That doesn?t mean that ADE can?t be operating, of course, just that we don?t have the solid evidence that it is. Another surprise in that line: there?s been a lot of talk about a possible protective effect of prior infection with the other respiratory coronaviruses. Well, there?s a flip side: antibodies raised against those could potentially make SARS-CoV-2 infection worse through ADE, if they?re non-neutralizing.
Now, there have been worries about ADE with coronavirus vaccines as well. This is another case where having all the work done against the 2003 SARS epidemic has paid big dividends this year. Some of the earlier attempts at a SARS vaccine showed ADE effects in mouse models, and further work showed that this seemed to be linked not so much to the antibody response as to the T cell response. Specifically, a ?Th2? heavy response (as opposed to more Th1 or a balance between the two), was linked to lung pathology. Those are subdivisions of the CD4+ T cells, based on which cytokines they produce, and these results alerted everyone to keep an eye out for that. Mouse immunogenicity studies with the current vaccine candidates did not show these effects.
In primate models, there were reports on the earlier SARS front like this one: four different peptides as vaccine candidates, three of which seemed to generate protective responses and one of which made things worse. But that also reminded everyone to watch carefully, and it has to be noted that the primate models for the current SARS-CoV-2 vaccines showed no signs of this, either. Not all the earlier SARS work in primates did, either: these two studies went well, with no ADE signs. But immunology being what it is, one has to watch carefully as you move into humans, and the clinical trials that we have been seeing read out have been alert to these possibilities. So far, so good.
This has been why we?ve seen so many vaccines taking care to put the Spike protein into its ?prefusion? conformation. The worry has been that if antibodies are generated to it after it?s had a chance to bind to human cells, that gives you a better chance for nonneutralizing ones (and thus potentially a better chance for ADE). And you?ll have noticed the emphasis on neutralizing antibody titers along the way as well ? that would have been there anyway, but a high proportion of outright neutralizing antibodies is also a safeguard against antibody-driven enhancement of disease.
At this point, I would say that the main worry for any ADE effects would be if the coronavirus mutates to the point that the antibodies generated by the current vaccines become non-neutralizing. And honestly, I don?t see that happening (it certainly doesn?t seem to have happened yet). Targeting the Spike protein is another big benefit that we got from the earlier SARS work; which suggested that (for example) targeting the Nucleocapsid (N) protein was riskier. With the Spike, you put the virus in an evolutionary tight spot: evading the antibodies while trying not to lose the ability to bind to the human ACE2 protein. So far, that looks like too narrow a path for the virus to stumble through.
160 comments on ?Antibody-Dependent Enhancement?
https://blogs.sciencemag.org/pipeline/archives/2020/12/18/antibody-dependent-enhancement
Antibody-Dependent Enhancement
By Derek Lowe 18 December, 2020
I?ve had several questions about antibody-dependent enhancement, which has always been a worry as the coronavirus vaccines have been developed. I figured it might be worth a look at just what we know about it, why one might be worried, and why (on the other hand) one might be hopeful.
The simple definition of ADE is ?raising antibodies that don?t protect, but actually make a viral infection even worse?. And obviously, that?s the opposite of what you want. Remember that there are ?neutralizing? antibodies as opposed to non-neutralizing ones ? a neutralizing antibody, as the name implies, binds to its target in a way that shuts its function down. That?s generally done by blocking the ?business end? of a given protein target, smothering the binding surface that it would need to do its usual job. For the coronavirus, a straightforward example of a neutralizing antibody would be on that binds to the tip of the Spike protein, the receptor-binding domain (RBD) that is the part that recognizes and binds to the human ACE2 protein on a cell surface. Block that thoroughly enough, and it would seem that you have blocked the virus?s ability to infect your cells.
There are other ways, as this blog post earlier this year makes clear (or tries to!) You don?t have to just completely cap the end of the Spike protein to shut it down ? as it turns out, you can bind an antibody further down the Spike and have it be neutralizing, just so long as it interferes with the structural changes that the Spike protein needs to undergo when it starts binding to a human cell membrane. There?s a whole subunit of the Spike (S2) that is involved in the membrane-fusion step, so throwing a wrench into that will work for you, too. Proteins make all sorts of adjustments as they fit to each other: this part has to shift down and over, that bond has to rotate, and some of those adjustments may be non-negotiable (and thus targets for blocking the whole process).
So there are plenty of ways to get neutralizing antibodies, with various ways of binding to the Spike protein and in binding to other coronavirus proteins as well. But there are also plenty of ways to get non-neutralizing antibodies, ones that stick to some part of the coronavirus particle without really inconveniencing it much. That?s obviously useless, and antibody-dependent enhancement takes things down another notch, from useless to outright harmful. With ADE, the binding of such an antibody actually assists the virus, by (for example) actually making it easier for the virus to get taken up through the outer membranes of human cells. Another possibility is that an antibody that would be neutralizing if present in sufficient amounts can actually enhance infection in lower dilutions, which has been seen with influenza antibodies and other viruses as well. This seems to be through aggregation of viral particles, although other factors might be at work.
You really don?t want ADE through any of these mechanisms ? bad things happen. Dengue fever is a classic example, because it infects humans through four distinct serotypes. If you are infected with one of these and raise a successful immune response, you may well be at increased risk of serious infection with one of the other serotypes. The neutralizing antibodies for one of the types are often not neutralizing for the others, but instead allow that cell-antibody-receptor mechanism to kick in (easier infection of human monocytes), known as ?extrinsic ADE?. There?s also an ?intrinsic ADE? seen with dengue, which leads to greater viral replication inside infected monocyte cells before they burst and release their contents. The mechanisms for that are still being worked out, but seem to involve suppression of cytokine pathways.
ADE has been seen with HIV infection (where it may be mediated by one of the complement pathways, which kicks in after an antibody binds to its target), with Ebola (where a completely different complement-driven mechanism seems to be operating), with coxsackievirus (and other picornaviruses), and in many others. It should be noted that inappropriate complement activation can cause troubles of its own, which can contribute to the severity of ADE-driven disease ? this is particularly noticeable in respiratory viruses (influenza and others) and their effects in the lungs.
Evolutionarily, you?d figure that developing such things would be under positive selection pressure: higher organisms are constantly fighting off viral infections by raising antibodies to them, so something that causes this to backfire would probably be an advantage for any virus that hits on such a mechanism. So ADE is not some weirdo exception in viral infections, unfortunately ? it?s pretty widespread.
And in the same way that viral infections can involve ADE, so can the antibody responses raised by vaccines. There was an inactivated-virus vaccine tried in the 1960s against RSV (respiratory syncitial virus) that in human trials actually caused infants to come down with worse cases of RSV. This effect has been duplicated with RSV in cell cultures and in primate models, and one hypothesis has been that (as with the extrinsic-ADE of dengue), the exposed regions of the antibodies bound to the viral particles bind in turn to receptors on human cell surfaces, and allow them to be taken into the cell more directly. A 1960s inactivated measles vaccine candidate showed similar effects.
Here?s a recent paper taking all this into the context of the current pandemic. And since this post up until now has been rather gloomy, you?ll be glad to hear that the news starts to improve at this point. For one thing, the current coronavirus does not seem to productively infect macrophages, which are by far the main target for that antibody-receptor-uptake ADE mechanism. The related MERS coronavirus was able to do this, but not SARS-CoV-2, fortunately. So the two mechanisms seen in (for example) dengue do not seem to be as much of a worry. The complement-driven stuff is still on the table, though, and indeed matches up well with the ?cytokine storm? lung damage seen in severe patients.
But as that new paper says, thus far ?No definitive role for ADE in human coronavirus diseases has been established.? That may be a bit surprising, if you?ve been seeing worried stories about antibody-dependent enhancement over the last few months. That doesn?t mean that ADE can?t be operating, of course, just that we don?t have the solid evidence that it is. Another surprise in that line: there?s been a lot of talk about a possible protective effect of prior infection with the other respiratory coronaviruses. Well, there?s a flip side: antibodies raised against those could potentially make SARS-CoV-2 infection worse through ADE, if they?re non-neutralizing.
Now, there have been worries about ADE with coronavirus vaccines as well. This is another case where having all the work done against the 2003 SARS epidemic has paid big dividends this year. Some of the earlier attempts at a SARS vaccine showed ADE effects in mouse models, and further work showed that this seemed to be linked not so much to the antibody response as to the T cell response. Specifically, a ?Th2? heavy response (as opposed to more Th1 or a balance between the two), was linked to lung pathology. Those are subdivisions of the CD4+ T cells, based on which cytokines they produce, and these results alerted everyone to keep an eye out for that. Mouse immunogenicity studies with the current vaccine candidates did not show these effects.
In primate models, there were reports on the earlier SARS front like this one: four different peptides as vaccine candidates, three of which seemed to generate protective responses and one of which made things worse. But that also reminded everyone to watch carefully, and it has to be noted that the primate models for the current SARS-CoV-2 vaccines showed no signs of this, either. Not all the earlier SARS work in primates did, either: these two studies went well, with no ADE signs. But immunology being what it is, one has to watch carefully as you move into humans, and the clinical trials that we have been seeing read out have been alert to these possibilities. So far, so good.
This has been why we?ve seen so many vaccines taking care to put the Spike protein into its ?prefusion? conformation. The worry has been that if antibodies are generated to it after it?s had a chance to bind to human cells, that gives you a better chance for nonneutralizing ones (and thus potentially a better chance for ADE). And you?ll have noticed the emphasis on neutralizing antibody titers along the way as well ? that would have been there anyway, but a high proportion of outright neutralizing antibodies is also a safeguard against antibody-driven enhancement of disease.
At this point, I would say that the main worry for any ADE effects would be if the coronavirus mutates to the point that the antibodies generated by the current vaccines become non-neutralizing. And honestly, I don?t see that happening (it certainly doesn?t seem to have happened yet). Targeting the Spike protein is another big benefit that we got from the earlier SARS work; which suggested that (for example) targeting the Nucleocapsid (N) protein was riskier. With the Spike, you put the virus in an evolutionary tight spot: evading the antibodies while trying not to lose the ability to bind to the human ACE2 protein. So far, that looks like too narrow a path for the virus to stumble through.
160 comments on ?Antibody-Dependent Enhancement?
https://blogs.sciencemag.org/pipeline/archives/2020/12/18/antibody-dependent-enhancement
<blockquote class="twitter-tweet"><p lang="en" dir="ltr">Democrat Rep. Rashida Tlaib partied last night with 100+ maskless people. Dems want your kids stuck in masks at school ALL DAY while they party maskless with their friends. Do not comply! Don?t give 1 more inch. In 2022 we WILL defeat the tyrants! Chip in: <a href="https://t.co/FGvUL6PziQ">https://t.co/FGvUL6PziQ</a> <a href="https://t.co/6lg71dtv2f">pic.twitter.com/6lg71dtv2f</a></p>— Robby Starbuck (@robbystarbuck) <a href="https://twitter.com/robbystarbuck/status/1424774759787769856?ref_src=twsrc%5Etfw">August 9, 2021</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
LOL. A bunch of vaccinated people partying together is somehow being compared to a bunch of unvaccinated children in close quarters. Apples to apples.
:mj07::mj07::mj07::mj07::mj07::mj07:<iframe scrolling="no" frameborder="0" allowtransparency="true" src="https://platform.twitter.com/widgets/widget_iframe.f88235f49a156f8b4cab34c7bc1a0acc.html?origin=https%3A%2F%2Fwww.madjacksports.com" title="Twitter settings iframe" style="display: none;"></iframe><iframe id="rufous-sandbox" scrolling="no" frameborder="0" allowtransparency="true" allowfullscreen="true" style="position: absolute; visibility: hidden; display: none; width: 0px; height: 0px; padding: 0px; border: none;" title="Twitter analytics iframe"></iframe>
<iframe width="450" height="351" src="https://www.youtube.com/embed/auSox6ybZD8" title="YouTube video player" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe>++++
Isn't that one of the doctors that said the vaccine makes you magnetic?
I hope the surgeons and doctors that wear masks every day hear that it's all been a waste and they can now stop wearing them. What a cost savings over time!
This guy is making his case for the Disinformation Dozen.
<iframe width="450" height="351" src="https://www.youtube.com/embed/zJKrGUOh5mw" title="YouTube video player" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe>++++
Nolte: New York?s Jim Crow Vaccine Passport Will Deny Service to 72% of Young Black Residents
A full 72 percent of young, black New Yorkers are about to be denied service and the right to work in New York City restaurants, gyms, and theaters.
The far-left New York Times reported Thursday only 28 percent of black New Yorkers aged 18 to 44 years are vaccinated, ?compared with 48 percent of Latino residents and 52 percent of white residents in that age group.?
This means that on September 13, when the fascist city?s vaccine passport law goes into effect, 72 of black New Yorkers aged 18-44 will be denied service, as well as 52 percent of young Hispanics.
[link to www.breitbart.com (secure)]
A full 72 percent of young, black New Yorkers are about to be denied service and the right to work in New York City restaurants, gyms, and theaters.
The far-left New York Times reported Thursday only 28 percent of black New Yorkers aged 18 to 44 years are vaccinated, ?compared with 48 percent of Latino residents and 52 percent of white residents in that age group.?
This means that on September 13, when the fascist city?s vaccine passport law goes into effect, 72 of black New Yorkers aged 18-44 will be denied service, as well as 52 percent of young Hispanics.
[link to www.breitbart.com (secure)]
- Mar 19, 2006
- 38,176
- 356
- 83
- 74
A picture of Antifa?
Track these LOSERS down and PROSECUTE them, where is the FBI on this matter or are they in on it?
Former PFIZER VP DR. MIKE YEADON, LATEST MESSAGE ? EVERYONE MUST LISTEN
Dr. Mike Yeadon Speaks
[link to www.bitchute.com (secure)]
Dr. Mike Yeadon Speaks
[link to www.bitchute.com (secure)]
My friend that exposed me to Covid 19 for the SECOND time has at least 4 stents, needless to say i'm worried for his health, he only gets his News "information" from the MSM.
Pity Really
Pity Really
- Status
