Thread by @NavroopSingh_

What is #ADE !

major goal of antibodies is to bind to the pathogen and prevent it from infecting, or entering, a cell. Antibodies that prevent entry into cells are called neutralizing antibodies. Many vaccines work by inducing neutralizing antibodies.

However not all antibody responses are created equal. Sometimes antibodies do not prevent cell entry & on rare occasions, they may actually increase the ability of a virus to enter cells & cause a worsening of disease through a mechanism called 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.

Neither COVID-19 disease nor the new COVID-19 vaccines have shown evidence of causing ADE. People infected with SARS-CoV-2, the virus that causes COVID-19, have not been likely to develop ADE upon repeat exposure.

This is true of other coronaviruses as well. Likewise, studies of vaccines in the laboratory with animals or in the clinical trials in people have not found evidence of ADE so far for vaccines. Though earlier Coronavirus vaccines for Sars CoV 1 showed ADE current ones havent.

Evaluation of the mRNA-1273 (Moderna) Vaccine against SARS-CoV-2 in Nonhuman Primates - July 28th 2020 - Study on ADE

The induction of CD4 type 2 helper T-cell (Th2) (interleukin-4, -5, or -13) responses has previously been associated with vaccine-associated enhanced respiratory disease (VAERD) in some children who were immunized with inactivated respiratory syncytial virus and measles vaccines.

To determine whether mRNA-1273 (Moderna) vaccine induced Th2 responses, researchers immunized macaques with two doses of either 10 mcg or 100 mcg of mRNA vaccine at four-week intervals and challenged the animals eight weeks later with SARS-CoV-2.

Vaccination with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. mRNA-1273 induced Th1 and not Th2 cell responses.

8 weeks after 2 doses of Moderna Vaccine Macaques were exposed to Sars-Cov-2 rapid neutralising antibodies were found in them in response to virus with no pathogenic changes in Lungs & Th1 T Cell response leading to robust immunity and no sign of ADE was detected.

A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and
2 prevents lung infection in non-human primates - Study on Pfizer Vaccine & ADE

Researchers reported the design, preclinical development, immunogenicity and anti-viral protective effect in rhesus macaques of the SARS-CoV-2 modified mRNA vaccine candidate, BNT162b2 (Pfizer BioNTech).

Animals inoculated with two doses of 100ug of mRNA. 7 days after the second dose, a robust Th1 response was observed, but only a minute Th2 response, consistent with the unlikely occurrence of vaccine-associated enhanced respiratory disease, which is associated with Th2 response.

Again no ADE was found in Pfizer vaccine.

Development of an inactivated vaccine candidate for SARS-CoV-2 & ADE (Inactivated ones are like COVAXIN or SINOVAC) -

Researchers developed a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2 specific neutralizing antibodies in mice, rats and nonhuman primates. The vaccine candidate was inactivated using β-propiolactone and mixed with alum adjuvant.

Three immunizations using two different doses provided partial or complete protection in macaques. After vaccination, macaques were challenged with SARS-CoV-2 without observable antibody-dependent enhancement of infection or immunopathological exacerbation.

Again No ADE was found even on Inactivated Virion Vaccines Platform. So all these fears of ADE so far not backed up by any conclusive study or data.

DNA vaccine protection against SARS-CoV-2 in rhesus macaques - Study & observation on ADE !

Researchers developed a series of six DNA vaccine candidates without adjuvant expressing different forms of the SARS-CoV-2 spike (S) protein and evaluated them in 35 rhesus macaques compared with placebo controls.

Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. The DNA vaccines induced Th1 rather than Th2 responses.

After vaccination, macaques were challenged with SARS-CoV-2 without observable enhanced clinical disease even with the suboptimal vaccine constructs that failed to protect against infection.

So across platforms be it mRNA or Viral Vectors or Inactivated Virus or DNA Vaccine no big sign of ADE reported and so scientific study to claim that. Yet the ADE risk is always there but we will need more data & see how situation involves going ahead to come to a conclusion.

A lot of Rumors have been made on COVAXIN probably causing ADE. Covaxin will use adjuvant Alhydroxiquim-II to boost immune response and longer lasting immunity.

COVAXIN also uses Imidazoquinoline class of adjuvants (TLR7/8 agonists), which are known to induce Th1 based response which further reduces the risk of ADE (Anti-Body Dependent Enhancement). Its Phase 3 data will put all the suspicion by usual quarters to rest.