3 ms·

I understand the concept of an attenuated strain. I don't see why the deletion mutants have to be found in the wild - it's easy enough to delete or modify gene

I understand the concept of an attenuated strain. I don't see why the deletion mutants have to be found in the wild - it's easy enough to delete or modify genes in the lab to create an attenuated strain. For example, some groups have replaced VSV's glycoprotein with the coronavirus spike protein. https://www.ncbi.nlm.nih.gov/pubmed/16043204 https://www.ncbi.nlm.nih.gov/pubmed/16043204 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103385/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103385/ And as I said, you can't know if the people who had mild infections did so because the virus was deficient or whether their immune response was good. It's not enough to have the antigen, you also need the right adjuvant to mount a response. The last thing you want is to have antibodies that recognize the virus, but do not activate the immune system. https://en.wikipedia.org/wiki/Antibody-dependent_enhancement#In_coronavirus_infection https://en.wikipedia.org/wiki/Antibody-dependent_enhancement... https://jvi.asm.org/content/94/5/e02015-19 https://jvi.asm.org/content/94/5/e02015-19 https://www.researchgate.net/publication/340005309_Potential_Mechanisms_of_Age_Related_Severity_of_COVID-19_Infection_Implications_for_Vaccine_Development_and_Convalescent_Serum_Therapy https://www.researchgate.net/publication/340005309_Potential... The fact that the live attenuated approach worked with polio doesn't mean that it'll work with coronavirus, and if we're not careful we could accidentally worsen the situation. I agree that this is worthwhile area of pursuit, but one that will take a long time to bear fruit. Maybe you think that studying the variants in the wild will allow us to skip over some animal studies with the live attenuated virus, but I doubt they can be skipped.

zamfi 7y ago
> deletion mutants have to be found in the wild I have no background in this whatsoever, so feel free to ignore my comment, but my guess is that finding them in the wild along with a large-enough (and representative-enough) infected population without severe symptoms basically saves the work of trying 5k different possible variant in animals — just skip the the promising candidate directly, no?
- pazimzadeh 7y ago
  I like the idea of pairing clinical data with virus sequence information from infected patients. That seems like medicine of the future. However, the PCR-based diagnostic tests that are current being used rely on amplifying only a small part of the virus genome so we are actually blind to how the rest of the virus is changing in the larger population (at least in routine diagnostic tests).
- danieltillett 7y ago
  That is right. We don’t know what mutations might make the virus attenuated (mild), but we can use what Nature has done to tell us. We also get human data on safety thrown in for free. This makes a huge difference in how quickly we can use a new strain in people even under controlled conditions.

zamfi 7y ago

> deletion mutants have to be found in the wild I have no background in this whatsoever, so feel free to ignore my comment, but my guess is that finding them in the wild along with a large-enough (and representative-enough) infected population without severe symptoms basically saves the work of trying 5k different possible variant in animals — just skip the the promising candidate directly, no?

pazimzadeh 7y ago
I like the idea of pairing clinical data with virus sequence information from infected patients. That seems like medicine of the future. However, the PCR-based diagnostic tests that are current being used rely on amplifying only a small part of the virus genome so we are actually blind to how the rest of the virus is changing in the larger population (at least in routine diagnostic tests).
danieltillett 7y ago
That is right. We don’t know what mutations might make the virus attenuated (mild), but we can use what Nature has done to tell us. We also get human data on safety thrown in for free. This makes a huge difference in how quickly we can use a new strain in people even under controlled conditions.