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.
4) We also tested several broadly reactive influenza mAbs from @PatWilsonLab, @TheBcellArtist and our lab to see if they can recognize these new proteins. A few anti-stalk mAbs bound to the HA, but only mAb IG01, a mAb binding to the active site of many NAs, recognized....
5) ...the NA. Finally, with @VivianaSimonLab we checked if there is any crossreactivity in polyclonal human sera to these new glycoproteins, but there was none. Here is the preprint: biorxiv.org/content/10.110…

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More from @florian_krammer

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
9 Nov 20
1) This morning, I shared an enthusiastic tweet about Pfizer's interim results with their COVID-19 vaccine. Let me explain here why am I am so enthusiastic, how the road to get this to people might look like and why we still need to control the pandemic NOW.
2) First, the results from the Phase III trial have to be seen in the context of pre-clinical, Phase I and Phase II trials. Preclinically, Pfizer shows the vaccine works in NHPs. Similar vaccines also worked. Also, in early clinical trials their vaccine induced good.....
3)....neutralizing antibody responses (that's what this vaccine does well). Now, in addition to that we get interim efficacy results that are in the 90% range. 90% is pretty good. It might even be higher. Could also be lower. But right now even a vaccine that affords.....
Read 16 tweets
28 Sep 20
1) SARS-CoV-2 Vaccines - I promised a Tweetorial and here we go. This is going to be long and nerdy. But I'll make sure it is easy to understand. If you want more details, please just read this: nature.com/articles/s4158…
2) I'll try to give an overview of the process, the technologies, correlates of protection, the candidates, how they perform in non-human primates and what we know about their performance in humans so far.
3) Let's start with the process. Developing vaccines usually takes a long time. Usually there is a medical need and some idea of how to design the vaccine, often in an academic lab. Versions of the vaccine are tested in iterative processes, the constructs are optimized....
Read 138 tweets
21 Jul 20
1) There is a lot of talk about decaying antibodies. I would like to walk you through a few findings about antibodies to SARS-CoV-2 that we put on medRxiv on Friday. Ill do this slowly over the day (while being in nonstop conference calls). But I feel this needs to get out there.
2) So, here is a link to that paper: medrxiv.org/content/10.110…. It is simple and pretty straight forward. Three figures only.
3) Before we start, two things: Acknowledgments and a primer in B-cell biology (a simple one):
Read 33 tweets
26 Jun 20
1) A lot of people see cases rising while deaths are going down in the US. Somebody who did not like my tweet earlier about the record cases today just pointed that out to me (and also calling me 'dipsh**'). So, I wanna tell a little story about Iran.......
2) There are many reasons why the CFR might go down. We test more, we find more cases. There might be many more younger people infected while older people are more careful and stay at home. Management of COVID-19 got better. There might be several more reasons.....
3) But I would be a little careful. So, Iran experienced a 'second wave' recently. Actually, it wasn't a second wave because the first one never went away. But anyways, after falling case numbers they started to rise again. I was curious about that on Twitter......
Read 6 tweets

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