Antibody Dependent Enhancement
1 Overview of Antibody Dependent Enhancement (ADE)
"ADE occurs when the antibodies generated during an immune response recognize and bind to a pathogen, but they are unable to prevent infection. Instead, these antibodies act as a “Trojan horse,” allowing the pathogen to get into cells and exacerbate the immune response."
"On a few occasions ADE has resulted from vaccination: RSV, Measles, Dengue virus:
Source: Children's Hospital of Philadelphia
"ADE is when a disease is made worse or more severe in a person who was already exposed to the virus through a previous infection or vaccination compared to people who were never exposed or vaccinated."
Source: British Columbia Vaccine Ministry
2 ADE Concerns and COVID-19
People who have had COVID-19 should only get 1 shot: "researchers found that people who had previously been infected with the virus reported fatigue, headache, chills, fever, and muscle and joint pain after the first shot more frequently than did those who had never been infected. Covid survivors also had far higher antibody levels after both the first and second doses of the vaccine. Based on these results, the researchers say, people who have had Covid-19 may need only one shot."
"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"
Source: Informed consent disclosure to vaccine trial subjects of risk of COVID-19 vaccines worsening clinical disease, March 2021
https://pubmed.ncbi.nlm.nih.gov/33113270/
"Live virus challenge of animals given SARS or MERS vaccines resulted in vaccine hypersensitivity reactions (VAH), similar to those in humans given inactivated measles or respiratory syncytial virus vaccines. Safe and effective COVID-19 vaccines must avoid VAH."
Source: COVID-19 Vaccines: Should We Fear ADE?, November 2020
https://pubmed.ncbi.nlm.nih.gov/32785649/
"One of the most perplexing questions regarding the current COVID-19 coronavirus epidemic is the discrepancy between the severity of cases observed in the Hubei province of China and those occurring elsewhere in the world. One possible answer is antibody dependent enhancement (ADE) of SARS-CoV-2 due to prior exposure to other coronaviruses."
Source: Is COVID-19 Receiving ADE From Other Coronaviruses?, March 2020
https://pubmed.ncbi.nlm.nih.gov/32092539/
"Antibody-dependent enhancement (ADE) may be involved in the clinical observation of increased severity of symptoms associated with early high levels of SARS-CoV-2 antibodies in patients."
"Current SARS-CoV-2 vaccines appear to be providing protection with high antibody titers; the possibility of ADE risks associated with waning titers of antibodies over time remains unknown."
"These models place increased emphasis on the importance of developing safe SARS-CoV-2 T cell vaccines that are not dependent upon antibodies."
Source: Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies, February 2021
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943455/
Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943455/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943455/pdf/fimmu-12-640093.pdf
"COVID‐19 vaccines worsening clinical disease: COVID‐19 vaccines designed to elicit neutralising antibodies may sensitise vaccine recipients to more severe disease than if they were not vaccinated. source"
Informed consent disclosure to vaccine trial subjects of risk of COVID‐19 vaccines worsening clinical disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645850/
"The development of multiple efficacious vaccines has been critical in the control of the pandemic, but their efficacy has been limited by the appearance of viral variants, and the vaccines can be associated with rare off-target or toxic effects, including allergic reactions, myocarditis, and immune-mediated thrombosis and thrombocytopenia in some healthy adults. Many of these phenomena are likely to be immune-mediated."
A Possible Role for Anti-idiotype Antibodies in SARS-CoV-2 Infection and Vaccination
https://www.nejm.org/doi/full/10.1056/NEJMcibr2113694
July 1, 2021: SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern
https://www.science.org/doi/10.1126/science.abi7994
July 30, 2021: Study explains how there are high probabilities of escape variants unless vaccination rate rises quickly: "Rates of SARS-CoV-2 transmission and vaccination impact the fate of vaccine-resistant strains"
https://www.nature.com/articles/s41598-021-95025-3
ADE could be seen with spike-directed vaccine candidates: "Our results suggest a novel mechanism by which SARS-CoV can enter target cells and illustrate the potential pitfalls associated with immunization against it."
Source: Anti-Severe Acute Respiratory Syndrome Coronavirus Spike Antibodies Trigger Infection of Human Immune Cells via a pH- and Cysteine Protease-Independent FcγR Pathway, October 2011
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3187504/
There was ADE trouble after immunization with a nucleoprotein-directed vaccine: "These results suggest that an excessive host immune response against the nucleocapsid protein of SARS-CoV is involved in severe pneumonia caused by SARS-CoV infection."
Source: Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV, November 2008
https://pubmed.ncbi.nlm.nih.gov/18941225/
Dr. Robert Malone: "The FDA called out Antibody Dependant Enhancement as a risk that was uncharacterized," "[The vaccinated] have the greatest risk in the waning phase of the immune response"
Source: "Vaccine-Enhanced Infection"
See media folder in Sources Archive for video
"due to cross-reaction to related coronavirus strains from earlier infections, the patient's viral history of coronavirus infection might be crucial to the severity of the course of the current infection with SARS-CoV-2, a phenomenon that has been called in the context of influence infections “original antigenic sin.” Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera."
Source: Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS
"These studies suggest that the antibodies produced in response to the vaccines that were developed based on early strains of SARS-CoV-2 could elicit ADE of infection for recent variants, including B.1.617.2 (delta) (27, 28). Additional studies are needed to evaluate how long ADE-inducing and neutralizing antibodies exist in vaccine recipients."
Source: Antibody-Dependent Enhancement of SARS-CoV-2 Infection Is Mediated by the IgG Receptors FcγRIIA and FcγRIIIA but Does Not Contribute to Aberrant Cytokine Production by Macrophages, September 2021
https://journals.asm.org/doi/10.1128/mBio.01987-21
"when SARS appeared in the human population back in 2003, there was a lot of work done on it to try to make vaccines . . . some of these candidate did show signs of ADE. When vaccinated animals were re-exposed to the same virus, some of them got even sicker than usual."
"the two big take-homes were that coronavirus vaccines could indeed suffer from ADE, and that this seemed to depend on which protein you chose to base your vaccine around."
Source: Antibody-Dependent Enhancement and the Coronavirus Vaccines, February 2021
https://www.science.org/content/blog-post/antibody-dependent-enhancement-and-coronavirus-vaccines
"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."
Source: Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus, 2012
https://pubmed.ncbi.nlm.nih.gov/22536382/
"Like other viruses with spike proteins on the viral surface, coronaviruses have been shown to elicit enhancement of disease through non-neutralizing spike protein-specific antibodies"
Source: Immunological characterizations of the nucleocapsid protein based SARS vaccine candidates, February 2006
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115648/
"Data from the study of SARS-CoV and other respiratory viruses suggest that anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through antibody-dependent enhancement (ADE)."
"Whether such cross-reactive antibodies can contribute to clinical ADE of SARS-COV-2 remains to be addressed."
Source: Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies
https://www.nature.com/articles/s41564-020-00789-5
"ADE has been observed in previous attempts to develop coronavirus vaccines. To add to the concern, antibodies typical of ADE are present in the blood of some COVID-19 patients. Such concerns are real."
https://www.scientificamerican.com/article/the-risks-of-rushing-a-covid-19-vaccine/
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