1) Dr. Paunic's excellent Tweet started a lot of discussions about how much we know about immune responses to SARS-CoV-2 vaccines in immunosuppressed patients. Of course, trials in some patient populations are under way. But, getting the results will take some time.....
2)...and there are so many different types and degrees of immunosuppression. Also, a lot of affected people are getting themselves tested for antibodies after vaccination. A systematic approach to collect and analyze all that data globally would be great.....
3)...and maybe somebody (a scientific society? a research team?) can take that on and generate a database to which physicians and patients can contribute data? Just throwing that idea out there.
4) If vaccine type, type of immunosuppression and type of antibody test are recorded, that would already give a ton of insights. If SARS-CoV-2 infections post vaccination (if they happen) are recorded, this would be even better. Of course, it would also be an IRB nightmare....

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More from @florian_krammer

7 Feb
1) Es geht hier nicht nur um Tirol. Es waere sehr wichtig B.1.351 (und in Zukunft aehnliche Varianten, speziell welche mit der E484K Mutation) schnell zu finden (aka alles Sequenzieren, und zwar innerhalb von Stunden, nicht Tagen)....
2)..., lokal zu Tracen und wenn noetig lokale Massnahmen zu treffen. Und zwar ohne politische Reibereien. Daten und Sequenzen muessen ohne Barrieren zwischen Bund und Laendern geteilt werden. Contact Tracing von Faellen muss schnell und reibungslos funktionieren.
3) Es geht ja nicht darum, ein Bundesland zu bestrafen, sondern darum solche Varianten schnell unter Kontrolle zu bringen. Vielleicht sollte man ein paar mobile Sequenzierlabors einrichten die man vor Ort schicken kann. Ich mein, ein MinION braucht recht wenig Platz.
Read 5 tweets
29 Jan
1) The low efficacy of the Novavax vaccine candidate against the B.1.351 is concerning. However, the data is also reassuring in many ways. First, the vaccine itself worked very well against the 'old' SARS-CoV-2 variants and the B.1.1.7 (UK) variant. Also, the vaccine...
2) ...seems to work almost as well in HIV positive individuals as in HIV negative individuals. And, vaccine efficacy against B.1.351 seemed markedly reduced, but still present. This was against symptomatic disease in general. It is very likely, that the efficacy against....
3)...severe disease is much higher. There are also some other things we can learn here. Novavax was reporting very high neutralization titers from their initial clinical phases, around 1:3500. Now, we see that there is a reduction in neutralization against B.1.351....
Read 11 tweets
26 Jan
1) So, this morning I promised a little tweetorial about variants and here we go. This will be from a vaccine/antibody point of view only, I won't comment on how infectious they are or if they are more pathogenic (I'll leave that to Boris Johnson 😉).
2) There are currently two variants for which there are insightful data sets. One is B.1.1.7 (aka the British variant) and the other one is B.1.351 (aka the South African variant). Let's start with B.1.1.7, which is easier. There is also more data. B.1.1.7 has a number of....
3)....mutations. Two are of special concern when it comes to vaccines since they might influence neutralizing epitopes. One is a change in position 501 (N501Y). This is located in the receptor binding domain of the virus were a lot of neutralizing antibodies bind. The other....
Read 44 tweets
5 Jan
1) We just put a really nice new preprint online about the HA and NA of the Wuhan spiny eel virus, a sister virus to influenza B that was discovered among many other new RNA viruses by RNA seq in 2016 by @edwardcholmes and colleagues (nature.com/articles/natur…).
2) Based on the sequences @Guha_Arunkumar and @Shirin_Strohm expressed the HA and NA recombinantly in the lab. @Guha_Arunkumar then nicely characterized them. It turns out - and this was done with the help of @RobertPdeVries1 and colleagues - that the HA binds very specifically..
3)...to a ganglioside (GM2) but not to regular glycans with terminal sialic acid. Very special! The NA turned out to be very similar in activity and specificity to influenza B virus NA.
Read 5 tweets
3 Jan
1) If we want to generate difficult viral escape mutants in the lab (e.g. for epitope mapping), we subject the virus to low antibody pressure and then slowly move up. A little bit like after one vaccine dose. I think it would be good to give the second dose as soon as possible.
2) I don't know if 12 weeks is going to be a huge issue, but that time frame should be minimized as much as possible. Also, there are good reasons for giving the second dose. It is likely that the second dose is needed to generate long lived and strong immunity.
3) But it will likely also drive affinity maturation of antibodies. This will make the antibodies stronger, and potentially will allow them to better cope with new variants.
Read 4 tweets
22 Dec 20
1) The biggest worry for vaccines about the new UK variant is the N501Y mutation in the receptor binding domain. This is also a mutation that appears when SARS-CoV-2 is mouse adapted. A paper looking at that found....
2)...that an experimental RBD-based vaccine still worked. I am not 100% sure the vaccine was based on N501, but I assume so. That would already be some good news. In general, I am not to worried about the impact of the new variant on vaccines. science.sciencemag.org/content/369/65…
3) The other thing to keep in mind is, that both the Pfizer and Moderna vaccines protected after one shot, when neutralizing antibodies were super low in the vaccinees, meaning that likely a low titer is sufficient for protection. Titers are very high after the second shot.....
Read 5 tweets

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