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.
4) It also depends on how much virus is circulating. If virus circulation is low, the 12 week window might not be a big problem. But if virus circulation is sky high (like right now in the UK), it is not a good idea. My 2 cents.

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More from @florian_krammer

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

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