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....
4)...of about 6-10-fold (depending on the preprint, for some even higher). That would result in a 1:350 neutralization titer. That's around the titers that Pfizer reported against the wild type strain. This could mean two things: The readouts of different neutralization assays...
5)...run in different labs are not comparable. Or, neutralizing antibodies are not the (only) correlate of protection. Or both. But it would be good if independent labs could run sera from several of the current vaccine trials and compare directly. Another important point is....
6)....and that it may be hard to extrapolate efficacy reduction from one vaccine to another. The Novavax data may indicate that the Pfizer and Moderna vaccines could also fall to 50% efficacy against some of these variants. Or the reduction could be much less...
7)....What also needs to be kept in mind is that the numbers are still small. Once numbers are accumulating, the picture may change a little. And let's not forget, 50% would not be great, but its MUCH better than nothing......
8)....especially if there is higher efficacy against severe disease. Let's wait for more data. And in the meantime, let's bring case numbers down.
9) PS: Since I was called pedantic today already on Twitter. It is Shabir Madhi, not Shabir Maddi. @Novavax ir.novavax.com/news-releases/…
2.1) I take the comment about efficacy in HIV+ individuals back. Sloppy reading and misinterpretation of the data on my side. Thanks to the people who were making me aware.
10) I take the comment about efficacy in HIV+ individuals back. Sloppy reading and misinterpretation of the data on my side. Thanks to the people who were making me aware. Apparently I am not pedantic enough.

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More from @florian_krammer

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
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

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