COVID Vaccine: Antibody Dependent Enhancement
One of the concerns with vaccines against SARS-CoV-2 has been something called antibody-dependent enhancement (ADE).
It is a paradoxical immune enhancement that occurs in people who were vaccinated against a specific virus, who when exposed to the wild type virus, experience a more severe infection.
It’s literally the opposite of what we want, right? The goal of vaccination is to result in either no infection or a very mild infection.
For many people, an infection with the wild virus SARS-CoV-2 is mild, so this is even more concerning that a vaccine can cause a worse course of disease than the virus in the wild.
ADE can increase the severity of multiple viral infections, including other respiratory viruses such as respiratory syncytial virus (RSV) and measles. ADE in respiratory infections is included in a broader category named enhanced respiratory disease (ERD), which also includes non-antibody-based mechanisms such as cytokine cascades and cell-mediated immunopathology. ADE caused by enhanced viral replication has been observed for other viruses that infect macrophages, including dengue virus and feline infectious peritonitis virus (FIPV). (1)
It’s a legitimate concern, and it’s something we won’t really have an answer for until more people are vaccinated, and then come in contact with the wild virus.
But we aren’t in the complete dark. Several years ago, there was a Dengue Vaccine Fiasco in the Philipphines, which resulted in a loss of over 600 children over a similar antibody-dependent enhancement.
In so many ways, we are guinea pigs, and this is the largest clinical trial in the history of medical science.
SOURCES:
“Our data suggest that vaccination with rMVA expressing SARS-CoV S protein is associated with enhanced hepatitis…”
2005 – Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses
“The entry of severe acute respiratory syndrome coronaviruses can be enhanced by [antibodies]…”
2005 – Neutralizing Antibody Response and SARS Severity
“The nonneutralizing antibodies are known to facilitate viral infection, termed antibody-dependent enhancement (ADE)…”
2006 – Animal models and antibody assays for evaluating candidate SARS vaccines: Summary of a technical meeting 25–26 August 2005, London, UK
“Enhanced disease and mortality have been observed in kittens immunized against or infected with a type-I coronavirus…”
“Children vaccinated with inactivated respiratory syncytial virus (RSV) vaccines developed serious disease on subsequent exposure to RSV…”
“In view of such examples of enhanced disease following infection in a vaccinated host, there has been heightened concern that a similar phenomenon could occur with SARS-CoV vaccines…”
“Prior immunization with (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV”
“Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge”
“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…”
2013 – A decade after SARS: strategies for controlling emerging coronaviruses
“There are currently no approved antiviral treatments or vaccines for human coronavirus infections…
Inactivated SARS-CoV vaccines have been administered to humans; the vaccines… induced the production of neutralizing antibodies, although the participants were all relatively young… and lung pathology was not assessed. Additionally, in the absence of a natural challenge, no data on vaccine efficacy are available…”
2014 – Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins
“We also generated monoclonal antibodies against SARS-CoV spike proteins and observed that most of them promoted SARS-CoV infection. Combined, our results suggest that antibodies against SARS-CoV spike proteins may trigger ADE effects. The data raises new questions regarding a potential SARS-CoV vaccine…”
“Evidence of antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro and in non-human primates clouds the prospects for a safe vaccine…
Safety concerns about a SARS-CoV vaccine have been raised, given the observation in vitro of antibody-dependent enhancement (ADE) of SARS-CoV infection that could, in theory, exacerbate disease…
This study demonstrates for the first time that an antibody (mAb43-3-14) targeting a specific linear epitope (S597–603) of the SARS-CoV spike protein can mediate enhancement of virus infection both in vitro and in non-human primates…“
2016 – SARS and MERS: recent insights into emerging coronaviruses
“One concern of vaccination in humans is vaccine-mediated enhancement of disease, a process in which the disease following infection is more severe in vaccinated individuals than in unvaccinated individuals…“
“Moreover, it is unclear who to vaccinate against MERS-CoV, as healthy individuals seem to be at little risk of severe disease. Older patients or patients with underlying disease, who have the highest risk of severe MERS, would be important target populations. However, vaccination in such patients can be problematic owing to their poor immune responses, as has been established for influenza virus…”
2018 – Viral-Induced Enhanced Disease Illness
“Unfortunately, clinical studies investigating ADE in SARS-CoV patients are limited…”
“Vaccine-induced disease enhancement is also a concern with developing a SARS-CoV vaccine…”
“Vaccines were able to protect against SARS-CoV infection, but still induced Th2 directed pulmonary immunopathology suggesting hypersensitivity to SARS-CoV components…”
“Post vaccination challenge of mice with SARS-CoV nucleocapsid protein induced severe pneumonia…”
“Double inactivated SARS-CoV vaccine in mice failed to provide complete protection and caused enhanced eosinophilic pro-inflammatory pulmonary response after infection…”
