Let it Glow. UK Vaccination responses with AZ and Pfizer.

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Today the COVID-19 story surfaces and DrRuth (BartsMS) and Emma T (Cardiff) share the limelight for what havs been a joint effort The rest are alphabetical and DrAngray should have been called Wang not Kang as he would be near the end.

This is the result of UK collaboration and looks at the vaccination response. I won’t post on the content yet but let Dr. Ruth or others do this but it shows results of dried blood spot tests that you helped us get off the ground. For us it started with the pandemic and we were busy in the lab trying to finish off the anti-drug antibody globody work with alemtuzumab

The alemtuzumab globody links the antigen-binding bit of alemtuzumab with the glow in the dark bit of deep sea shrimp vomit (abilt like a firefly glow but brighter). This complexes with the anti-drug antibody in blood and this complex is captured by a molecule called protein G that was originally stuck to plastic. You make the glow in the dark molecule emit light and measure it. The protein G captures all the antibody in the blood. So if there are complexes of globody and anti-globody in the blood the anti-drug antibodies are marked and can be detected.

So along comes COVID-19 and we are kicked out of the lab, Dr.Angry says he can adapt the GloBody assay to detect COVID-19 responses. The powers that be said we had to get a grant to do it before we could get in the lab to do work, which we didn’t need money to do. But we wasted a few months getting support from Barts Charity.

So DocA designed DNA of a COVID-19 protein linked to the glow in the dark molecule. The first GloBody we made was against nucleocapsid (one of the 4 proteins expressed by SARS-CoV-2) and we (i.e. Dr Angry) made enough for 2 million tests within 2 days. This shows infection

With the Leyton Triangle of researchers (Kang, Rose, Maine) it could have been enough for all of the UK and Ireland and more within a week.

Dr. Angry also made a GloBody against the receptor binding domain of the Spike protein. This is the bit used to allow the virus to infect human cells. In life the Spike molecule exsists as a trimer of three spike molecules so DocA added a trimerization site so three glow in the dark molecules are added. We used this to show vaccination response

pictures made with Biorender.com

Otherwise it is the same assay as the anti-drug antibody response.

To work on COVID you have to work in a containment facility, but we realised if we put on a dried blood spot, the virus is dead within 3 days on paper and we could punch a bit of blood from the card into a detergent that ensures we kill every virus and so we can safely work on the bench. This would allow us to test responses in people with MS, without the need to go to hospital. ProfG (Sponsored marathon round London streets and then sponsored rehabilitation after the life threatening accident) and Kit (Sponsored swim round cornish beaches) raised the cash via crowdfunding for us to send out the blood spot card. We used student power to do the work. Only more recently pharma has come to the show to let us.

We heard that our collaborators on the anti-drug stuff in Cardiff, who were working with Nottingham and other places in Wales, was doing something similar to us but they were using the more standard method of virus detection. Rather than compete we joinded forces with the groups from Wales to get a much broader view of what is going on and it confirms the smaller studies that people taking anti-CD20 and fingolimod have issues in making antibodies and this is not helped by people taking Astrazeneca vaccine for some of the other treatments.

This has now given us a method to now measure antidrug responses in MS without the need for hospital visits.

COVID-19 vaccine response in people with multiple sclerosisTallantyre, E. C., Vickaryous, N., Anderson, V., Asardag, A. N., Baker, D., Bestwick, J. P., Bramhall, K., Chance, R., Evangelou, N., George, K., Giovannoni, G., Grant, L., Harding, K. E., Hibbert, A., Ingram, G., Jones, M., Kang, A. S., Loveless, S., Moat, S., Robertson, N. P., Schmierer, K., Shah, S. N., Simmons, J., Upcott, M., Willis, M. D., Jolles, S., Dobson, R.10.1101/2021.07.31.21261326 — Posted: 2021-08-01

Objective: To investigate the effect of disease modifying therapies on serological response to SARS-CoV2 vaccines in people with multiple sclerosis Methods: 473 people with multiple sclerosis from 5 centres provided one or more dried blood spot samples and a questionnaire about COVID-19 and vaccine history. Information about disease and drug history was extracted from their medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV2 receptor binding domain. Seropositivity was expressed according to validated cut-off indices. Antibody titers were partitioned into tertiles using data from people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (Univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following SARS-CoV2 vaccine according to disease modifying therapy. We used regression modelling to explore the effect of factors including vaccine timing, treatment duration, age, vaccine type and lymphocyte count on vaccine response. Results: Compared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio 0.03; 95% confidence interval 0.01-0.06, p<0.001) and fingolimod (odds ratio 0.41; 95% confidence interval 0.01-0.12) were associated with lower seroconversion following SARS-CoV2 vaccine. All other drug groups did not differ significantly from the untreated cohort. Both time since last anti-CD20 treatment and total time on treatment were significantly related with serological response to vaccination. Vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications. Interpretation: Some disease modifying therapies carry a risk of attenuated response to SARS-CoV2 vaccination in people with MS. We provide recommendations for the practical management of this patient group.

General Disclaimer: Please note that the opinions expressed here are those of authors and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice. Disclaimer:

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MouseDoctor

11 comments

  • I wondered whether the incredibly complex work for MS and others would contribute significantly to the COVID-19 puzzle. Let’s hope the treatment of Covid-19 will help the unravelling of MS too.

  • Dear MD
    Thank you very much for posting this. I have tried to dig through the data in the paper for information on alemtuzumab – I think per Table 1 there were 28 people in total who were sampled after 2nd vaccine (23 at Cardiff and 5 at QMUL according to supplementary table 1) of which 24 seroconverted and 4 who didn’t per Table 2. (I’m not sure the QMUL split of positive/negative seroconversion in supplementary table 1 is correct because it says 3 were positive and 2 negative in which case if Cardiff is correct with 22 positive and 1 negative overall 25 serovonverted and 3 didn’t? or else at QMUL 2 were positive and 3 negative??).

    My question is how long after treatment did seroconversion take – Alaistair Coles said in the video with MS Trust it takes 2 years after treatment – which looks about right given the very long median length of time after treatment (676.5 days or nearly 2 years per Table 1)?

    • Thhanks remember it is a preprint and so there could be a mistake….I’ll pass this on. In terms of the alemtuzumab I am not sure of the interval between dose and vaccine. I think seroconversion will occur much quicker than 2 years as the B cells come back so quickly. I would also want to see the AZ pfizer breakdown as some of the failers in some of the non-CD20/fingolimod cohort were I think more common in AZ

  • Aww not looking good for anti CD20 ☹

    Y’know it’s amazing to get this out there so quickly, huge thanks to Dr A, Dr Ruth and of course all the crowd funders!

    • You can click on the link to read the report….it looks like Dr Ruth has gone on holiday so I may do my take when I have some time

  • MD – a question. I had 2 doses of the AZ vaccine at 1 and 4 months post my ocrevus infusion. Month 5 i caught covid. Im 90% recovered now but my next infusion is due next week. Will this reset me completely or should i still benefit from the 2 jabs plus infection?

    • I believe the next ocrelizumab will not reset you, you have made a T cell response and that remains and hopefully that helped you recover, sadly I suspect you made no B cell response because of the ocrelizumab

      • Thanks for the reply MD. Hopefully the infection boosted my T-cell response further but what does this mean for the prospect of reinfection? reinfection rates remain low but presumably this is due to the antibody response, which may still not exist for me

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