Thread by @veeslerlab

Are you wondering what antibody responses are like in #SARSCoV2 Delta breakthrough patients?

We answer this question and many others in this study led by @coronalexington

@HHMINEWS @UWBiochemistry

biorxiv.org/content/10.110…

1/15

We followed 4 cohorts longitudinally for up to 6 months:
-Delta breakthrough (vaccinated then infected)
-subjects infected and then vaccinated (2x and 3x)
-vaccinated-only (2x and 3x)
-infected-only

in collaboration with @HelenChuMD and her HAARVI team.

2/15

Serum IgG binding titers correlated with the number of SARS-CoV-2 spike 'exposures' through vaccination and/or infection and were therefore highest for 3x vaccinated subjects (infected or not) and Delta breakthrough cases.

3/15

We observed a similar trend for SARS-CoV-1 cross-reactive sarbecovirus antibody binding responses, which roughly correlated with SARS-CoV-2 binding titers, but not with embecovirus (OC43/HKU1) binding titers that remained unchanged across all cohorts.

4/15

These latter data correlate with our previous observations that fusion machinery (S2)-directed antibodies, such as those recognizing the stem helix, are rare in the memory B cell repertoire of infected or vaccinated individuals.

5/15

science.org/doi/10.1126/sc…

We observed highly potent and durable serum neutralizing activity against #SARSCoV2 ancestral (G614) S pseudovirus for Delta breakthrough and infected/vaccinated subjects. 3x vaccination of naive individuals led to comparably potent neutralizing responses, great news!

6/15

Elicitation of potent neutralizing antibody responses through repeated 'exposures' also enhanced resilience
to mutations observed in variants of concern, such as Delta and Beta, for Delta breakthrough cases, infected/vaccinated subjects and 3x vaccinated individuals.

7/15

Neutralization of the more genetically divergent SARS-CoV-1 S pseudovirus, however, is a lot tougher (24-36x reduction of inhibition). Infected individuals that were 3x vaccinated stood out the most in this assay.

8/15

These data support strongly administrating a 3rd vaccine dose to people who have not been previously infected but also emphasize the challenges associated with eliciting broad immunity even 'just' within the sarbecovirus subgenus.

9/15

Fortunately, @coronalexington has been working on this and is already designing vaccines eliciting broader sarbecovirus immunity and protection in collaboration with @KingLabIPD @Baric_Lab

10/15

sciencedirect.com/science/articl…

So is @David_RMartinez in the @Baric_Lab

11/15

science.org/doi/10.1126/sc…

And @bjorkmanlab

12/15

science.org/doi/10.1126/sc…

Finally our study builds on early work of infected/vaccinated subjects from @McGuire_Lab

13/15

science.org/doi/10.1126/sc…

And @PennyMo70026063

14/15

sciencedirect.com/science/articl…

Thank you very much Kaiti Sprouse, Anshu Joshi, @johnbowenbio, Mary -Jane Navarro, @Dr_MattMcCallum and all our other collaborators including @GreningerLab @SkiClimbSciNick

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