Antibody Dependent Enhancement (ADE) was an early concern for many scientists who weren’t fixated on giving Covid vaccines to everyone. However, anything suggesting that mRNA vaccines weren’t a gift from God was dismissed. Worse than that, it wasn’t even studied or looked at.

ADE occurs when suboptimal antibodies, acting almost like a Trojan Horse, bind a virus and enhance its entry into cells. This can happen in both natural infection and vaccination and can result in more severe disease.

Now, a new Japanese re-evaluation of ADE of infection in Nature Scientific Reports confirms that ADE could be causing adverse effects.

These novel mRNA vaccines have been developed to target the SARS-CoV-2 spike protein (S-protein). The authors say that whilst the preventative and therapeutic effects of vaccine antibodies are obvious, little attention has been paid to the influence of the remaining and dwindling anti-S-protein antibodies. They found that, whilst mRNA (Moderna) antibodies initially exhibited neutralising activity, a dominance of ADE activity was observed over time.

When examining how long neutralising or ADE activities lasted, they found that no neutralising activity was detected 27 days after first vaccination. The highest concentration of neutralising activity was detected on days 20 - 52 after the second vaccination.

ADE activity was also detected at diluted concentrations. After day 98 of the second vaccination, no neutralising activity was detected, however clear ADE activity was maintained.

Taken together, these results demonstrate that after vaccinations, neutralizing antibodies are induced and persist for a long time in some individuals, but ADE-causing antibodies also exist from the early stage and persist for a longer period than do neutralizing antibodies in some individuals. It is noteworthy that ADE observed at a higher concentration of serum, that is at low dilution (1/100), might mean a more vulnerable stage in terms of susceptibility to infection, because no neutralizing activity was detected.

Next, the authors of the paper examined the effect of vaccination against Omicron. They found that whilst some samples maintained neutralising activity against the original strain on day 175 after vaccination, there was no neutralising activity against Omicron. One sample still exhibited ADE activity.

It is suggested that the rapid spread of Omicron around the world may be in part due to the lack of cross-neutralisation against Omicron and some ADE activity after vaccination.

They conclude by saying that their study shows that mRNA vaccination targeting the S-protein has potential to cause ADE. Their experiments show that the opposing activities of neutralisation and ADE are exhibited by the same antibodies.

Interestingly, the amount of virus seemed to be unrelated to the development of ADE. Infection was enhanced even with an extremely low dose of virus. They also suggest that ADE-causable antibodies are not the only critical factor that results in the development of ADE.

Whilst it is plausible that unfavourable ADE causing antibody concentrations may not be reached until the virus has been cleared from the body, the authors say it is still important to pay attention to the possible adverse effects caused by remaining or diminishing anti-SARS-CoV-2 antibodies.

Furthermore, due to the protective effects of T-cell immunity it might make it more difficult to recognise ADE in reinfections.

Antibodies raised by double vaccination (at least on day 175 after the second vaccination) are less effective against Omicron as reported, and suggest that the Omicron strain has acquired the ability to escape attack by pre-existing anti-SARS-CoV-2 Abs and in part can utilize infection-enhancing mechanisms, possibly including ADE, as a means of survival.

It leads one to wonder how many people experienced ADE after vaccination from small amounts of virus, which would not have caused a problem if they had remained unvaccinated. How many people may have died as a result of ADE? All speculation but speculation which is supported by this Japanese study. Speculation, which if left uninvestigated, may cause similar or worse problems in future vaccination campaigns.

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