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Pulling directly from TFA, > Here we show that this lineage exhibits complete escape from three classes of therapeutically relevant monoclonal antibodies. Furt

by Arubis 6y ago

Pulling directly from TFA, > Here we show that this lineage exhibits complete escape from three classes of therapeutically relevant monoclonal antibodies. Furthermore 501Y.V2 shows substantial or complete escape from neutralizing antibodies in COVID-19 convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines. Ugh; this hurts to read. The callouts there are "complete escape [from] convalescent plasma" (prior exposure won't help you), and "reduced efficacy of current spike-based vaccines" (which is all of the ones deployed, I believe).

UncleOxidant 6y ago
Yeah, this is not great news. I hope the vaccine makers are looking at adding coverage for these variants to the existing vaccines. That should be relatively easy to do for the mRNA vaccines, but possibly harder for the adenovirus based vaccines like the Oxford/AZ and the J&J. The question is whether they would have to go through a full phase 3 trial for this kind of addition or would this be more like how we add coverage to different flu viruses to the annual flu vaccines?
- ashtonbaker 6y ago
  > That should be relatively easy to do for the mRNA vaccines That isn't super obvious to me anymore, after it was pointed out to me that the current mRNA vaccines rely on a modified sequence for the spike protein, designed to make the protein stable enough to be usable in the vaccine process (described here [1] as "antigen S-2P" - "S" for "Spike" and "2P" for the two proline substitutions in the sequence). It's my understanding that this work dates to 2017 [2], and that it might not be quick or easy to replicate for new spike protein variants. [1] https://www.nature.com/articles/s41577-020-00480-0 https://www.nature.com/articles/s41577-020-00480-0 [2] Pallesen, J. et al. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc. Natl Acad. Sci. USA 114, E7348–E7357 (2017).
AndrewBissell 6y ago
> The callouts there are "complete escape [from] convalescent plasma" (prior exposure won't help you) Whether prior exposure helps also depends on T-cell response. At this point it's well established that immunity lasts for some unknown period of time past when most antibodies have left the bloodstream.
ianai 6y ago
exiting discussion
- rimliu 6y ago
  It will never be the new normal and there ate no reasons for it to be.
- woofie11 6y ago
  ... or rapid iteration of vaccines. The Moderna vaccine was ready in approximately a day, at least as a first draft. All of the work was in regulatory, validation, etc. My hope is that we can validate and approve minor tweaks to the vaccine much more quickly.
etiam 6y ago
Sure hope we're not globally in the process of inducing maladaptive immunity to emerging strains that turn out to get extensive spread... https://en.wikipedia.org/wiki/Original_antigenic_sin https://en.wikipedia.org/wiki/Original_antigenic_sin

by Arubis 6y ago

UncleOxidant 6y ago

Yeah, this is not great news. I hope the vaccine makers are looking at adding coverage for these variants to the existing vaccines. That should be relatively easy to do for the mRNA vaccines, but possibly harder for the adenovirus based vaccines like the Oxford/AZ and the J&J. The question is whether they would have to go through a full phase 3 trial for this kind of addition or would this be more like how we add coverage to different flu viruses to the annual flu vaccines?

ashtonbaker 6y ago
> That should be relatively easy to do for the mRNA vaccines That isn't super obvious to me anymore, after it was pointed out to me that the current mRNA vaccines rely on a modified sequence for the spike protein, designed to make the protein stable enough to be usable in the vaccine process (described here [1] as "antigen S-2P" - "S" for "Spike" and "2P" for the two proline substitutions in the sequence). It's my understanding that this work dates to 2017 [2], and that it might not be quick or easy to replicate for new spike protein variants. [1] https://www.nature.com/articles/s41577-020-00480-0 https://www.nature.com/articles/s41577-020-00480-0 [2] Pallesen, J. et al. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc. Natl Acad. Sci. USA 114, E7348–E7357 (2017).

AndrewBissell 6y ago

> The callouts there are "complete escape [from] convalescent plasma" (prior exposure won't help you) Whether prior exposure helps also depends on T-cell response. At this point it's well established that immunity lasts for some unknown period of time past when most antibodies have left the bloodstream.

ianai 6y ago

exiting discussion

rimliu 6y ago
It will never be the new normal and there ate no reasons for it to be.
woofie11 6y ago
... or rapid iteration of vaccines. The Moderna vaccine was ready in approximately a day, at least as a first draft. All of the work was in regulatory, validation, etc. My hope is that we can validate and approve minor tweaks to the vaccine much more quickly.

etiam 6y ago

Sure hope we're not globally in the process of inducing maladaptive immunity to emerging strains that turn out to get extensive spread... https://en.wikipedia.org/wiki/Original_antigenic_sin https://en.wikipedia.org/wiki/Original_antigenic_sin