Florian Krammer Profile picture
Viruses, viruses, viruses and vaccines. V2=vaccinated twice Professor at the Department of Microbiology Icahn School of Medicine at Mount Sinai
Domingo Gallardo Profile picture Karen Horton Profile picture Κασσάνδρα Παρί پری Profile picture John Miller Profile picture Mark Wintle Profile picture 81 added to My Authors
1 Apr
@MarcusFahn A) Virale Glykoproteine sind oft kleine Maschinen, die die Fusion der viralen Membran und der Zellmembran ermoeglichen. Erst dann kann das virale Genom in unsere Zellen rein und anfangen die Kontrolle zu uebernehmen. Diese Protein binden and unsere zellulaeren Rezeptoren....
@MarcusFahn B).....in der 'Praefusionskonformation'. Dann aendert sich diese Konformation schlagartig in die 'Postfusionskonformation' und dabei werden die virale und die Zellmembran verbunden. Stellen sie sich einfach eine Stahlfeder vor, die zusammengedrueckt ist und von einer Klammer....
@MarcusFahn C)...gesichert wird. Das ist die 'Praefusionskonformation'. Wird die Klammer entfernt, springt die Stahlfeder schlagartig auf. Das waere dann die 'Postfusionskonformation'. Jetzt ist es so, dass Antikoerper die die Praefusionskonformation binden oft stark neutralisierent....
Read 7 tweets
1 Apr
1) Ein paar Infos zu Sputnik V, weils grad alle interessiert. Der Impfstoff ist eine Kombination aus zwei Adenovirus Vektoren, und zwar Adenvirus Typ 5 und Adenovirus Typ 26. Adenovirus Typ 26 is selten, da gibts wenig Vektorimmunitaet die Probleme bereiten kann....
2).....Wenn wir von Vektorimmunitaet sprechen, geht es um neutralisierende Antikoerper gegen das Vektorvirus selbst. Wenn man viele davon hat, wird der Vektor neutralisiert bevor er in unsere Zellen eindringen kann und das wirkt sich negativ auf die Immunantwort....
3)...aus. Weil wenn weniger Vektor in die Zellen kommt, wird weniger SARS-CoV-2 Spike Protein hergestellt und dann ist die Immunantwort schwaecher. Wie gesagt, bei Ad26 Vektoren kein Problem. Bei dem Schimpansenadenovirus das von AstraZeneca eingesetzt wird auch nicht, ....
Read 10 tweets
15 Mar
1) The NDV-S vaccine that Peter Palese's lab (with some help from Adolfo García-Sastre's and my lab) developed was injected into first volunteers today in Vietnam (Phase I). @McLellan_Lab contributed his HexaPro construct.
vtv.vn/video/ban-tin-… (starts at minute 2:16)
2) The vaccine is based on an NDV vector that has SARS-CoV-2 spike on its surface. This version of the vaccine is inactivated (a life, intranasal version is in development as well) and can be produced at low cost in existing influenza vaccine production capacity.
3) And it worked very well in protecting mice and hamsters from SARS-CoV-2 challenge. Here are some references for anybody interested. ncbi.nlm.nih.gov/pmc/articles/P… and ncbi.nlm.nih.gov/pmc/articles/P…
Read 4 tweets
27 Feb
1) There are a lot of questions about how fully vaccinated individuals should behave. I don't have good solutions either, but I have some thoughts. First of all, we are seeing more and more data about how well vaccination works in a real live setting. There are recent studies...
2) ...from Israel (nejm.org/doi/full/10.10…; thelancet.com/journals/lance…) and Scotland (papers.ssrn.com/sol3/papers.cf…) showing high vaccine effectiveness in the population. That is just awesome and a reason to celebrate for all of us. On the other side you need to keep in mind....
3)...that vaccination, while highly effective, doesn't remove all risk. There are cases of symptomatic infection even after two vaccinations, keep that in mind. These cases might be mild, but they can occur. The protection you can expect from being vaccinated is driven....
Read 15 tweets
14 Feb
1) Ich hab einen Vorschlag. Der AstraZeneca Impfstoff wirkt gegen alle in Europa zirkulierenden SARS-CoV-2 Viren ausser B.1.351. Aber B.1.351 ist bisher selten, auch in Gegenden wo man es in Europa detektiert hat (z.B. Tirol). Jetzt gibts viel Widerstand gegen den Impfstoff....
2)....und alle wollen die RNA Impfstoffe. Von denen gibts aber nicht genug im Moment. Eine der Hauptsorgen ist, dass es nicht klar ist ob man mit einem an Varianten angepassten RNA Impfstoff auf AstraZeneca 'draufimpfen' kann wenns notwendig wird bzw....
3)....wenn sich rausstellt dass die 'normalen' RNA Impfstoffe gegen alle Varianten gut wirken, ob man dann mit denen nachimpfen kann wenn man schon den AstraZeneca Impfstoff bekommen hat. Aus immunologischer Sicht waere sowas vermutlich kein Problem. Ganz im Gegenteil....
Read 11 tweets
10 Feb
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.
Read 4 tweets
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
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
6 Jun 20
1) Nipah virus is another virus to keep an eye on. It doesn't transmit between people well but it can to a certain degree, it has a high CFR and there are regular outbreaks. One vaccines is in clinical trials (funded by CEPI).
2) CEPI is funding clinical trials for vaccines against emerging viruses including Lassa, Nipah Marburg, MERS, Chikungunya, CCHF etc. CEPI is financed by Norway, Japan, Germany, the Gates Foundation and the Wellcome Trust. India is planning to contribute.
3) These CEPI-funded vaccines will potentially avoid future pandemics. The US is not contributing. Maybe tell you representatives that it would be a good idea to change that. cepi.net
Read 4 tweets
25 May 20
@Docjoshsoc @angie_rasmussen 1) Titer matters. The lower respiratory tract is protected by IgG, the higher your serum IgG, the better. The upper respiratory tract is protected by IgA1, so having mucosal antibodies helps a lot too. High titers matter because they can stop the virus right....
@Docjoshsoc @angie_rasmussen 2) ....when it enters your body. Memory B cells are pretty useful too, but they first need to react and become plasmablasts. For fast acting viruses like influenza this mechanism might contribute to getting less sick, but will likely not prevent you from getting sick.......
@Docjoshsoc @angie_rasmussen 3) ....But since SARS-CoV-2 has a longer incubation period, the plasmablast response (generated from memory B cells) will maybe have a bigger impact. Plasmablasts kick usually in after 5-7 days, which is approximately the mean incubation time of SARS-CoV-2.....
Read 4 tweets
6 May 20
1) I wanted share some data from a manuscript that just wen online at medrxiv.org/content/10.110…. This was spearheaded by the fantastic Dr. Ania Wajnberg in collaboration with many parts of the Mount Sinai Hospital and Icahn School of Medicine.
2) The data describes PCR and serology findings in the first 1343 plasma donors screened at Mount Sinai. Initially, there were two groups of donors: people who at some point had PCR confirmed COVID19 and people who had suspected COVID19 (but were never PCR confirmed).
3) The majority of these donors were mild cases. Now, almost all PCR-confirmed donors had antibodies, while the majority of the suspected COVID19 individuals did not. This tells us two things: a) the assay works and b) many people who think they had COVID19 might not have had it.
Read 10 tweets
22 Apr 20
1) So, this is the first 'serious' preclinical data I have seen for an actual vaccine candidate. This one is an inactivated SARS-CoV-2 vaccine made by Sinovac. Seems to work in NHPs. biorxiv.org/content/10.110…
2) Their vaccine is in Phase I trials in China already. The company was also the only company that made a SARS-classic vaccine back then and pushed it into Phase I trials (NIAID had one as well, but they are not a company). Looked good back then too: intmedpress.com/serveFile.cfm?…
3) Here is the link to their Phase I/II trial registration: clinicaltrials.gov/ct2/show/NCT04… This is old-fashioned technology but that would make it easy to do it in other plants that manufacture inactivated vaccines too. I am a fan.
Read 4 tweets