In an effort to condense 15-20 years of research into 1 year or less, Covid-19 vaccine developers are going straight to human trials without safety results from animal trials. Animal trials of previously developed experimental coronavirus vaccines showed that the vaccines made the effects of virus exposure (“challenge”) worse via an effect called immune enhancement. Human test subjects will not be challenged with COVID-19 as part of the experiments, meaning the potential for this effect will not be studied. Consider the following quotes straight from the scientific literature:
SARS-CoV in Mice:
- “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/file?id=10.1371/journal.pone.0035421&type=printable - “Therefore, not only did N vaccination fail to control SARS-CoV replication within the lungs, but N vaccination also resulted in an enhanced immunopathology in the lungs of the senescent animals upon viral challenge.”
https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.0030525&type=printable - “These results indicate that not only did the DIV vaccine fail to protect from viral replication and morbidity/mortality, but the vaccine actually promoted the development of enhanced inflammatory damage within the lungs.”
https://jvi.asm.org/content/jvi/85/23/12201.full.pdf - “At 9 days postinfection, the… immunized groups exhibited severe pulmonary inflammation…. These results suggest that the severe pulmonary inflammation seen in m8rVV-NMES-immunized mice after SARS-CoV infection results from host immune responses rather than a direct cytopathic effect of SARS-CoV….”
https://www.jimmunol.org/content/jimmunol/181/9/6337.full.pdf - “Immunization of adult mice with UV-V, with or without alum, resulted in partial protection from lethal doses of SARS-CoV challenge, but extensive eosinophil infiltration in the lungs was observed.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135953/pdf/zjv8597.pdf
SARS-CoV in Ferrets:
- “Here, we found that immunization with rMVA-S is associated with enhanced hepatitis in ferrets after SARS-CoV challenge…. Extra caution should be taken in proposed human trials of SARS vaccines (9) due to the potential liver damage from immunization and virus infection.”
https://jvi.asm.org/content/jvi/78/22/12672.full.pdf - “…vaccination did not prevent SARS-CoV infection in ferrets. In contrast, immunized ferrets (particularly those immunized with rMVA-spike) exhibited significantly stronger inflammatory responses and focal necrosis in liver tissue after SARS-CoV challenge than control animals. Thus, our data suggest that enhanced hepatitis is linked to vaccination with rMVA expressing SARS-CoV antigens.” “…we would like to suggest that extra caution must be taken in future human trials of SARS vaccines due to the potential organ damage resulting from immunizations.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115540/pdf/main.pdf
SARS-CoV in Macaques:
- “In SARS-CoV/macaque models, we determined that anti– spike IgG (S-IgG), in productively infected lungs, causes severe ALI [acute lung injury] by skewing inflammation-resolving response.” “Deceased SARS patients displayed higher levels of serum NAbs [neutralizing antibodies], accumulated proinflammatory, macrophages infiltration, and absence of wound-healing macrophages in the lungs.” “Moreover, significantly higher levels of anti-S NAbs were detected in the sera of deceased patients (n = 6) during acute infection compared with recovered patients (n = 8)….” “…modulation of the anti-S antibody response or blockage of Fcγ receptors during acute infection might be needed for effective treatment for respiratory CoV infection.”
https://insight.jci.org/articles/view/123158/pdf
SARS-CoV in African green Monkeys:
- “Findings from this study support a role for the immune response in contributing to SARS-CoV pathogenesis, as enhanced inflammation and lung leukocyte activation was observed long after viral clearance.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318632/pdf/zjv4234.pdf
MERS-CoV in Mice:
- “Inactivated MERS-CoV vaccine appears to carry a hypersensitive-type lung pathology risk from MERS-CoV infection that is similar to that found with inactivated SARS-CoV vaccines from SARS-CoV infection.”
https://www.tandfonline.com/doi/pdf/10.1080/21645515.2016.1177688?needAccess=true
Feline Infectious Peritonitis Virus:
- “When kittens were immunized with the recombinant, low titers of neutralizing antibodies were obtained. After challenge with feline infectious peritonitis virus, these animals succumbed earlier than did the control group…. (early death syndrome).”
https://jvi.asm.org/content/jvi/64/3/1407.full.pdf - “Kittens vaccinated… were not protected against oronasal challenge exposure with virulent virus. In fact, kittens vaccinated with avirulent virus were more readily infected than were nonvaccinated cats.”
https://www.researchgate.net/publication/16897427_Attempted_immunization_of_cats_against_feline_infectious_peritonitis_using_avirulent_live_virus_or_sublethal_amounts_of_virulent_virus - “Non-immune kittens passively immunized with serum containing a high titer of antibodies reactive against FIPV developed an enhanced disease when later challenged with virus. Compared to kittens pretreated with non-immune serum, the FIPV antibody-sensitized kittens developed clinical signs earlier and died more rapidly after infection.“
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134169/pdf/main.pdf - “These results demonstrated antibody-dependent enhancement (ADE) of FIPV infection in macrophage. The replication of FIPV 79-1146 strain in macrophages from FIPV antibody-positive cats was more enhanced than in those from antibody-negative cats.”
https://link.springer.com/content/pdf/10.1007/BF01310476.pdf - “Our results are consistent with the hypothesis that antibody-dependent enhancement of feline infectious peritonitis virus infectivity is mediated by antibody directed against specific sites on the spike protein.”
https://jvi.asm.org/content/jvi/66/2/956.full.pdf - “Only about half the kittens that were seronegative before inoculation developed disease or serum antibodies to the tissue-derived virus. Seronegative kittens that developed disease showed no signs of illness until 8 to 10 days after inoculation, and they lived for 7 to 14 days after clinical signs appeared…. In contrast, all of the seropositive kittens became ill within 36 to 48 hours after inoculation, and died within 5 to 7 days…. The temporal relationship of clinical disease and the appearance of serum antibodies, the more acute and severe nature of the disease produced in seropositive kittens, and the presence of antibody and complement in the lesions indicated that effusive FIP is immunologically mediated.”
https://pubmed.ncbi.nlm.nih.gov/6254400/ - “These findings suggested that FIPV replication in macrophages increases TNF-alpha production in macrophages, and the produced TNF-alpha acts and upregulates fAPN expression, increasing FIPV sensitivity.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103289/pdf/main.pdf - “A total of 15 of the neutralizing MAbs [monoclonal antibodies] induced ADE [antibody dependent enhancement]…. Two S-specific MAbs induced ADE but were nonneutralizing.”
https://jvi.asm.org/content/jvi/66/11/6695.full.pdf - “In view of the potential of DNA vaccines to induce cell-mediated responses, their efficacy to induce protective immunity in cats was evaluated. The membrane (M) and nucleocapsid (N) proteins were chosen as antigens, because antibodies to the spike (S) protein of FIP virus (FIPV) are known to precipitate pathogenesis. However, vaccination by repeated injections of plasmids encoding these proteins did not protect kittens against challenge infection with FIPV…. Because of the role of IL-12 in initiating cell-mediated immunity, the effects of co-delivery of plasmids encoding the feline cytokine were studied. Again, IL-12 did not meet expectations – on the contrary, it enhanced susceptibility to FIPV challenge. This study shows that DNA vaccination failed to protect cats against FIP and that IL-12 may yield adverse effects when used as a cytokine adjuvant.”
https://www.microbiologyresearch.org/docserver/fulltext/jgv/83/1/0830001a.pdf?expires=1598840570&id=id&accname=guest&checksum=284889F8F1FE5122ECE46DC2B0048440
On SARS-CoV-2 (Covid-19 virus) in humans:
- “We argue that ADE should be given full consideration in the safety evaluation of emerging candidate vaccines for SARS-CoV-2.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187142/pdf/41577_2020_Article_321.pdf - “Non-neutralizing antibodies to variable S domains may enable an alternative infection pathway via Fc receptor-mediated uptake. This may be a gating event for the immune response dysregulation observed in more severe COVID-19 disease. Prior studies involving vaccine candidates for FCoV5,6 SARS-CoV-17-10 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) demonstrate vaccination-induced antibody-dependent enhancement of disease…. Sequence and structural conservation of S motifs suggests that SARS and MERS vaccine ADE risks may foreshadow SARS-CoV-2 S-based vaccine risks.” “Safety testing of COVID-19 S protein-based B cell vaccines in animal models is strongly encouraged prior to clinical trials to reduce risk of ADE upon virus exposure.”
https://www.preprints.org/manuscript/202003.0138/v1 - “All SARS-CoV-2 immunogenic epitopes have similarity to human proteins except one…. [which] might be responsible for autoimmunological pathogenic priming due to prior infection or following exposure to SARS-CoV-2 or relatives following vaccination.”
https://www.sciencedirect.com/science/article/pii/S2589909020300186#:~:text=Failure%20of%20SARS%20and%20MERS,will%20lead%20to%20similar%20outcomes. - “While the molecular and immunological host response to SARS-CoV-2 infection has not yet been fully elucidated to confirm ADE is occuring, the current clinical evidence suggests this is a possibility.” “Should ADE be proven to be a mechanism of pathogenesis, both treatment regimens and vaccine development will need to take this phenomenon into consideration to ensure it is mitigated and in the case of a vaccine, avoided altogether.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102551/pdf/main.pdf
On SARS-CoV in humans:
- These observations, if corroborated with further analysis of data collected in other countries, should raise the concerns of possible ADE in the pathogenesis of SARS-CoV infection in humans and should be considered in the process of vaccine development.
https://wwwnc.cdc.gov/eid/article/11/11/04-0659_article - “These data show that the entry of severe acute respiratory syndrome coronaviruses can be enhanced by Abs [antibodies], and they underscore the need to address the evolving diversity of this newly emerged virus for vaccines and immune therapies.”
https://www.pnas.org/content/pnas/102/3/797.full.pdf - “We demonstrate here that anti-Spike immune serum… potentiated infection of immune cells by SARS-CoV Spike-pseudotyped lentiviral particles, as well as replication-competent SARS coronavirus.” “Our experiments conclusively demonstrate with several lines of evidence that both SARS-CoVpp and replication-competent SARS-coronavirus infect certain immune cells only in the presence of anti-Spike immune serum and not in its absence.” “It is believed that an antibody-mediated infection pathway could provide SARS-CoV additional entry routes, allowing the virus to broaden its tropism.”
https://jvi.asm.org/content/jvi/85/20/10582.full.pdf - “Combined, our results suggest that antibodies against SARS-CoV spike proteins may trigger ADE effects. The data raise new questions regarding a potential SARS-CoV vaccine, while shedding light on mechanisms involved in SARS pathogenesis.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092860/pdf/main.pdf - “These results demonstrate that human macrophages can be infected by SARS-CoV as a result of IgG-mediated ADE….”
https://virologyj.biomedcentral.com/track/pdf/10.1186/1743-422X-11-82 - “Entry into human B cell lines occurred in a FcRII-dependent and ACE2-independent fashion indicating that ADE of virus entry is a novel cell entry mechanism of SARS-CoV.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115629/pdf/main.pdf - “An upsurge of antibody response is associated with the aggravation of respiratory failure that required ventilator support.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016775/pdf/03-0367.pdf - “Taken together, these findings suggest that the lung damage at this phase is related to immunopathological damage as a result of an overexuberant host response, rather than uncontrolled viral replication.”
https://www.thelancet.com/action/showPdf?pii=S0140-6736%2803%2913412-5 - “…while complement-inactivated sera from immunised animals still inhibit SARS-CoVpp entry in prototypic permissive cell lines, these sera induced virus penetration in human monocytic and lymphoblastic (B lineage) cell lines….” “Antibody-dependent enhancement of SARS-CoV infection, in addition to other alternative entry pathways (involving C-type lectin), may provide SARS-CoV versatility in entry routes allowing it to broaden its target options.”
https://www.hkmj.org/system/files/hkm1202sp2p31.pdf - “Our study has shown that “early” seroconversion… occurred more frequently among patients who required ICU-admission. In addition, higher IgG levels were detected in patients who had more severe diseases as evidenced by need for either supplemental oxygen or ICU-admission…. Peak IgG titres also correlated positively with peak LDH levels (an indicator of disease severity) among survivors.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108264/pdf/main.pdf - “Taken together, our results show that RBD[receptor binding domain]-specific neutralizing MAbs bind to the same region on coronavirus spikes as viral receptors do, trigger conformational changes of the spikes as viral receptors do, and mediate ADE through the same pathways as viral-receptor-dependent viral entry.”
https://jvi.asm.org/content/jvi/94/5/e02015-19.full.pdf
General:
- “Previous immunization by vaccination or infection might aggravate symptoms of a follow up infection….” “Even after nearly 20 years of vaccine research for SARS-CoV and 10 years for MERS-Cov, there are still not any approved vaccines and anti-viral treatments available (51), particularly due to severe complications encountered during animal testing (24).”
https://onlinelibrary.wiley.com/doi/epdf/10.1002/cyto.a.24047 - “During viral infection, pulmonary architecture is frequently compromised primarily by the host immune response and to a lesser extent directly by virus replication in most cases.”
https://link.springer.com/content/pdf/10.1007/s00281-016-0558-0.pdf
We Are Change Chicago 