This study shows that as antibody levels drop, antibody-dependent enhancement can be a factor in enhanced infectivity of SARS-CoV-2. The authors took convalescent antibodies from recovered COVID patients and studied the role of different Fc receptors in mediating this effect.
https://twitter.com/justinaloe/status/1443703707288301599
These findings are concerning, as they suggest that below certain thresholds of neutralizing antibodies, “off-target” antibodies can enhance infectivity.
I worry that as we give boosters against older strains of COVID, the risk of this occurring clinically may also increase. It shouldn’t be controversial to state this, and this isn’t to suggest that vaccines aren’t necessary for saving lives.
The next generation of vaccine platforms should actively consider these data and what we know about infection-enhancing antibodies, and should promote hyper-specific presentation of only the epitopes that promote neutralizing antibody formation.
Otherwise, we also run the risk of novel strain emergence whereby, upon antibody levels waning, the ratio of neutralizing antibodies decreases while the ratio of infection enhancing antibodies increased.
Note, I am not suggesting that the current vaccines are not efficacious. Vaccination *does* induce a tremendous neutralizing antibody response, much more so than natural recovery. And, this risk of ADE is present from natural exposure to SARS-CoV-2 and recovery from COVID-19.
@FDACBER should consider these data in terms of designing and rapidly approving boosters that promote the appropriate epitopes for maximizing neutralizing antibody responses to current and emerging strains, not just the original outbreak strain.
Additionally, we should develop and deploy more rapid testing that can differentiate between strains, as well as determine neutralizing antibody versus infection-enhancing antibody levels. We need to be aggressively gathering these data and preempting worst-case scenarios.
Finally, we should be quantitating neutralizing antibody levels in vaccinated individuals as well as vaccinated + naturally recovered individuals. Vaccination followed by exposure to and recovery from a new strain of the virus creates similar antibody titers to double vax.
These antibodies e.g. against recovery from the delta variant will be more tuned to new strains, while benefitting from the primary (or secondary) immune response generated from vaccination.
There are a lot of data floating around, and there is much misinformation. Do get vaccinated if you can, as this is the best way to protect yourself and those you care about. The studies are clear that “natural immunity” carries a higher risk of reinfection than vaxed immunity.
Here are a few more threads worth exploring:
https://twitter.com/nanogenomic/status/1382725260148043780
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