Thread by @michaelmina_lab

Severe #COVID19 resulting from Original Antigenic Sin??

May be a contributor. Makes sense

Superb paper evaluating cross-reactivity between donor B cells targeting SARS-CoV-2 and other seasonal Coronas.

This figure (2) is really depicts it well...

1/

medrxiv.org/content/10.110…

This figure depicts one persons different B cells (x axis) across 3 different weeks in time, and how they react to SARS2 spike (y axis - broad categories) and how the secreted antibodies from those B cells reacts with other seasonal coronaviruses (y axis - smaller categories)

2/

What is remarkable is the change over time from day 9 to day 16 in the binding of antibodies to the seasonal coronavirus OC43 by B cells elicited by exposure to the SARS-CoV-2 Spike ectodomain (S ecto).

3/

At day 9 of COVID19 infection, this person had a bunch of B cells, primarily targeting SARS-CoV-2 and not so much OC43. However, as the infection wore on, an abundance of B cells came out of the Woodward to bind OC43 as well.

4/

While these could simply be cross reactive B cells raised against Secto of SARS2, they may indicate “back boosting” of B cells previously raised against OC43....

This backboosting is consistent with an idea of “original antigenic sin”

5/

Original Antigen Sin or OAS is a phenomena where a response to a new pathogen is distracted by previous immune memories to related known pathogens

This distraction can boost memory against the previous virus, at the expense of a diminished response to the new pathogen

6/

The back boosted B cells may not be particularly helpful to fight off the new pathogen (sometimes they could be (ie protective cross reactivity) but sometimes not and if it reduces the ability to develop proper immunity to the new pathogen, we suggest it is original antigenic sin

This terrific new preprint I’m discussing here ☝️is by first author Brenda Westerhuis, and senior authors @MarionKoopmans and Gijsbert P. van Nierop among numerous others!

*woodwork :)

Severe SARS-CoV-2 may be associated with original antigenic sin, as discussed in the paper. But doubtful is the only or even major contributing factor. Nevertheless understanding OAS is crucial for vaccine design, therapy & further refining understanding of this and other viruses

Plus would be delighted to hear from any of the authors on their take on the contribution of OAS to the severity. Necessary but not sufficient perhaps? Simply extra but not necessary for severe SARS2?