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Not sure this helps us much. The problem is augmentation. A vaccine could take a healthy young person who would have had an asymptomatic infection, and change t
by Gatsky 7y ago
Not sure this helps us much. The problem is augmentation. A vaccine could take a healthy young person who would have had an asymptomatic infection, and change that into severe disease. Infecting them with an attenuated strain doesn't give enough certainty about the risk of augmentation with the real thing.
It is also a large effort to produce a medical grade attenuated strain that you could infect people with in a trial.
- danieltillett 7y agoI think you are referring to ADE (antibody dependent enhancement). This is a function of the vaccine, not the virus. The idea here it to use a strain you know is safer than one you know is more dangerous. For a challenge trial you only need enough virus for a few thousand people at most. It is not difficult to produce this amount of virus in cell culture.
- Gatsky 7y agoYes although antibodies aren’t the only mechanism. I’m not worried about post-vaccine enhancement with the attenuated strain, I’m worried that you can’t reliably demonstrate the vaccine doesn’t cause enhancement after the real infection.
- danieltillett 7y agoThis problem exists with or without finding an attenuated strain. A better way to think about this is let’s say we had two strains of the virus isolated - one that killed 10% of people infected and the other that killed less than 0.0001%. Which one should we use in a challenge trial?
- Gatsky 7y agoI’m not sure what your point is. Ultimately you need to demonstrate a vaccine is safe and efficacious for the real disease. An attenuated strain isn’t the real disease.
- danieltillett 7y agoNo you don’t if you choose the right attenuated strain, but even if you decided for some insane reason that you had to test the vaccine with a pathogenic strain you do this after you have shown that the vaccine protected the vaccinated person from the attenuated strain.
- Gatsky 7y agoHow do you know you’ve chosen the right attenuated strain?
- lbeltrame 7y agoFTR, at least the preprint written by SinoVac about their inactivated vaccine (which is in Phase 1, and Phase 2 beginning shortly IIRC), claims that they observed no ADE in rhesus macaques.