Thank you. I was looking forward to your newsletter this morning for rational and easy to understand scientific forecast on Omicron. Chag Sameach. I'll have to look for that book for my grandkids.
My biggest question is: what exactly is the regulatory pathway for an updated vaccine, should one be required? Will the FDA want a full phase III trial again? Or just safety and immunogenicity data, as with the 5-11 trial? How large will the sample need to be?
Relatedly, what does this mean for kids' vaccines? Adolescents had to wait half a year after the first EUA, younger kids almost an entire year. Children under 5 still have nothing. It seems like it would be ill-advised from a public health perspective, as well as more than a little cruel, to make children and parents wait that long again.
Great question. While I don't think an explicit regulatory pathway has been established, I believe that the approval of a vaccine in children on the basis of immunobridging has established that changes in formulation do not require full efficacy trials. In other words, we can use some established correlate of protection or other immune marker of vaccine effect, based on a known-protected population, to establish that the new population with the new version of the vaccine is protected.
This would work as follows: if it is established that variant X meaningfully escapes prior immunity, then a formulation to immunize against variant X would be created. The level of neutralizing antibodies that were required to protect against prior variants has been studied. We would then check that patients receiving a booster against variant X have a neutralizing antibody titer after this boost that is comparable to what we saw in protected patients with past variants.
This is similar to what is done for seasonal influenza vaccines, and it makes sense to use that same approach here. I am hoping that the FDA will use that approach for the updating of COVID-19 vaccines.
Similarly, a simultaneous trial at the children's dose with the same immunological type of endpoint I've just described could be run. I don't think anyone will have to wait longer, if the FDA does this similarly to how they operate for influenza vaccines. It remains to be seen if that is the approach they will take, but I would be pretty surprised if they chose not to use this method.
Thank you. I was looking forward to your newsletter this morning for rational and easy to understand scientific forecast on Omicron. Chag Sameach. I'll have to look for that book for my grandkids.
Chag Sameach!
My biggest question is: what exactly is the regulatory pathway for an updated vaccine, should one be required? Will the FDA want a full phase III trial again? Or just safety and immunogenicity data, as with the 5-11 trial? How large will the sample need to be?
Relatedly, what does this mean for kids' vaccines? Adolescents had to wait half a year after the first EUA, younger kids almost an entire year. Children under 5 still have nothing. It seems like it would be ill-advised from a public health perspective, as well as more than a little cruel, to make children and parents wait that long again.
Great question. While I don't think an explicit regulatory pathway has been established, I believe that the approval of a vaccine in children on the basis of immunobridging has established that changes in formulation do not require full efficacy trials. In other words, we can use some established correlate of protection or other immune marker of vaccine effect, based on a known-protected population, to establish that the new population with the new version of the vaccine is protected.
This would work as follows: if it is established that variant X meaningfully escapes prior immunity, then a formulation to immunize against variant X would be created. The level of neutralizing antibodies that were required to protect against prior variants has been studied. We would then check that patients receiving a booster against variant X have a neutralizing antibody titer after this boost that is comparable to what we saw in protected patients with past variants.
This is similar to what is done for seasonal influenza vaccines, and it makes sense to use that same approach here. I am hoping that the FDA will use that approach for the updating of COVID-19 vaccines.
Similarly, a simultaneous trial at the children's dose with the same immunological type of endpoint I've just described could be run. I don't think anyone will have to wait longer, if the FDA does this similarly to how they operate for influenza vaccines. It remains to be seen if that is the approach they will take, but I would be pretty surprised if they chose not to use this method.