Will Prof G have to eat his proverbial hat?
I have been telling people that an effective SARS-CoV-2 vaccine is a long way away and that we shouldn’t expect a commercially available vaccine for another 12-18 months. Maybe I am wrong. The Moderna phase 1 results were published by the NEJM yesterday and are more impressive than I expected. These results are so important because the vaccine is based on RNA technology, which is relatively easy to scale-up in terms of production, unlike recombinant protein vaccines or inactivated viral vaccines. Therefore this vaccine may be with us before the end of the year.
The Moderna RNA vaccine carries the code for S-2P antigen, consisting of the SARS-CoV-2 glycoprotein. The vaccine is given as two doses (Day 1 and Day 29) into the deltoid or shoulder muscle. The RNA then uses the molecular machinery of the deltoid muscle to make the immunogen that then stimulates the immune response to the antigen, which will hopefully prevent wild-type SARS-CoV-2 infection and prevent COVID-19.
This has potential implications for how we treat MS. It increases the likelihood of a successful vaccine to prevent COVID-19 and increases the chances of pwMS having to be vaccine-ready in a 6-9 month time scale rather than a 12-18 months period. Clearly this has implications for how we manage patients on DMTs that have been shown to blunt or prevent protective vaccine responses, in particular, pwMS on anti-CD20 therapy (rituximab, ocrelizumab, ofatumumab) or S1P-modulators (fingolimod, siponimod, ozanimod, ponesimod).
Will Prof G have to eat humble pie or his hat? The market response to the data below suggests he will. What will be the implications for the MS DMT market? I suspect an effective coronavirus vaccine will hit the anti-CD20 market the most, which means ofatumumab’s MS launch will be a damp squib.
Jackson et al. An mRNA Vaccine against SARS-CoV-2 — Preliminary Report. NEJM July 14, 2020 DOI:10.1056/NEJMoa2022483
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.
METHODS: We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group.
RESULTS: After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events.
CONCLUSIONS: The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461
CoI: multiple
I’m a patient who was hoping to start ocrelizumab as my first DMT. I’m not sure which one to go for now! And I doubt enough of the general population would be willing to have the vaccine to be able to rely on a herd immunity sort of effect. 🙁
Why not use the same technology for the flu vaccine?
Yes, there is a lobby who has wanted to change the flu vaccine paradigm. This may be the catalyst we need.
Pfizer also reported Ab induction with their RNA vaccine at 30 x2 doses or 100 x1 dose.
This isn’t specific to your post today Prof G, but there is a lot in the news about specific T cells from past coronaviruses potentially providing some protection.
Do people on anti CD20 have this T cell immunity from coronaviruses they had before they started the DMT? Or are they gone too?
Thanks and sorry for my basic understanding issues!
Don’t know. I am not aware that these studies have been done. But anti-CD20ers are unlikely to make neutralizing anti-coronavirus antibodies in response to common community-acquired coronaviruses, which is one hypothesis to explain why they are at higher risk of getting COVID-19 and severe COVID-19.
But what about common colds and coronaviruses they had before they were on anti CD20? Antibodies they had developed prior to treatment do they still have those?
That they do but seems coronavirus antibodies don’t hang around that long.
What are the implications for someone treated with Alemtuzumab? I had second round 1-3rd June this year
Thanks for your helpful work , Prof G.
How long in advance one should stop Ocrelizumab to be ready for the vaccine?
I will get soon my 5th infusion of Ocrevus…
It depends on your body size and B-cell repletion kinetics. We think you will need to miss one, two or even three infusions. I suspect your peripheral B-cell counts will need to be above 20/mm3 and possibly above 80/mm3 (lower limit of normal). We have proposed testing this in the COVAX study?
https://multiple-sclerosis-research.org/2020/06/mscovid19-covax-or-coronavirus-ocrelizumab-vaccination-study/
If a person’s first Ocrevus was postponed in March days before lockdown…
And then the hospital been back in touch to do the the blood tests again…..
should that person stear clear of it because of a potential vaccine looking sooner rather than later then?
Not sure how to answer this question; you need to discuss it with your HCP. MS needs to be treated and I wouldn’t wait for the vaccine if I had MS. However, there are other treatment options that will leave you more likely to be vaccine ready if a vaccine becomes available.
Wouldn’t hang on for a vaccine IMO, no guarantee one will be ready soon or how effective one will be.
Hi, another Ocrevus patient here. I am trying to think about this using my own lab results. Where would one’s CD19, CD20, and Lymphocyte absolute values need to be for a vaccine to work? For instance, I delayed my latest infusion by 6 weeks due to COVID-19, and my CD19 and CD20 had already repopulated to 44 cells/uL (normally I’m at about 9 cell/uL after exactly 6 months). The same values as you said above: at least 20/mm3 and ideally above 80/mm3? I seem to be a fairly fast repopulator (even though I have a low-normal body mass index). And THEN, how long after a vaccine would one need to wait until the next infusion? THANK YOU.
Lower limit of normal is 80 cells/ul.
How long to wait from vaccine to next infusion…I dont know but once you seroconvert you have converted and you have plasma cells that will not be affected by ocrelizumab. I suspect the time interval is not that long
I’m sure ProfG will be happy if it’s proved that his initial hypothesis was wrong!
In light of new evidence and better understanding of the virus, would it be possible to have the MS-Selfie DMT table updated?
Thank you! I was looking for info regarding how if being on Copazone for RRMS would have to be considered when I’m able to get a COVID 19 Vaccine. It looks like I don’t have to worry about Copazone and the effectiveness of a COVID 19 vaccine; even though I realize there are 2 different types in trials.
yes I doubt copaxone will influence the development of a vaccine response