The Oxford University/AstraZeneca vaccine has been approved for use for people 18 years or older and consists of two doses, with the second dose administered 4-12 weeks after the first dose. The transportation and storage requirements for this vaccine mean that it needs to be kept at temperatures of 2C to 8C, which is similar to a conventional fridge for up to six months and can be administered within existing healthcare settings.
The UK Government has purchased 100 million doses of this and it likely to be the vaccine that most of us get offered
As with any vaccine or medicine, COVID-19 vaccines require continuous safety monitoring by the MHRA and that the benefits in protecting people against COVID-19 must be greater than any side-effect or potential risks.
The name is: COVID-19 Vaccine AstraZeneca
The dose is: 50 billion viral particles i.e. the full dose
The COVID-19 Vaccine AstraZeneca vaccination course consists of two separate doses of 0.5 ml each. The second dose should be administered between 4 and 12 weeks after the first dose
Immunocompromised individuals. It is not known whether individuals with impaired immune responsiveness, including individuals receiving immunosuppressant therapy, will elicit the same response as immunocompetent individuals to the vaccine regimen.
Pregnancy:There is a limited experience with the use of COVID-19 Vaccine AstraZeneca in pregnant women.Preliminary animal studies do not indicate direct or indirect harmful effects. Administration of COVID-19 Vaccine AstraZeneca in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and foetus (More tests are needed). Breastfeeding: It is unknown whether COVID-19 Vaccine AstraZeneca is excreted in human milk. But antibodies can get in to breast milk
Side effects The most frequently reported adverse reactions were injection site tenderness (>60%); injection site pain, headache, fatigue (>50%); myalgia (muscle ache), malaise (>40%); pyrexia (fever), chills (>30%); and arthralgia (joint ache), nausea (>20%). The majority of adverse reactions were mild to moderate in severity and usually resolved within a few days of vaccination. By day 7 the incidence of subjects with at least one local or systemic reaction was 4% and 13% respectively. When compared with the first dose, adverse reactions reported after the second dose were milder and reported less frequently. (Not sure why)
Adverse reactions were generally milder and reported less frequently in older adults (≥65 years old).
If required, analgesic (anti-pain) and/or anti-pyretic (anti fever) medicinal products (e.g. paracetamol-containing products) may be used to provide symptomatic relief from post-vaccination adverse reactions.
Mechanism of action
COVID-19 Vaccine AstraZeneca is composed of a single recombinant, replication-deficient chimpanzee adenovirus (ChAdOx1) vector encoding the S glycoprotein of SARS CoV 2. Following administration, the S glycoprotein of SARS CoV 2 is expressed locally stimulating neutralising antibody and cellular immune responses.
Clinical efficacy
COVID-19 Vaccine AstraZeneca has been evaluated based on an interim analysis of pooled data from four on-going randomised, blinded, controlled trials: a Phase I/II Study, COV001, in healthy adults 18 to 55 years of age in the UK; a Phase II/III Study, COV002, in adults ≥18 years of age (including the elderly) in the UK; a Phase III Study, COV003, in adults ≥18 years of age (including the elderly) in Brazil; and a Phase I/II study, COV005, in adults aged 18 to 65 years of age in South Africa. The studies excluded participants with history of anaphylaxis or angioedema (Swelling); participants with severe and/or uncontrolled cardiovascular, gastrointestinal, liver, renal, endocrine/metabolic disease, and neurological illnesses; as well as those with immunosuppression. In studies COV001 and COV002, licensed seasonal influenza and pneumococcal vaccinations were permitted (at least 7 days before or after their study vaccine).
Based on the pre-defined criteria for interim efficacy analysis, COV002 and COV003 exceeded the threshold of ≥5 virologically confirmed COVID-19 cases per study and therefore contributed to the efficacy analysis; COV001 and COV005 were excluded.
In the pooled analysis for efficacy (COV002 and COV003), participants ≥18 years of age received two doses of COVID-19 Vaccine AstraZeneca (N=5,807) or control (meningococcal vaccine or saline) (N=5,829). Because of logistical constraints (cock-up with the manufacturing and supply) , the interval between dose 1 and dose 2 ranged from 4 to 26 weeks.
Baseline demographics were well balanced across COVID-19 Vaccine AstraZeneca and control treatment groups. Overall, among the participants who received COVID-19 Vaccine AstraZeneca, 94.1% of participants were 18 to 64 years old (with 5.9% aged 65 or older); 60.7% of subjects were female; 82.8% were White, 4.6% were Asian, and 4.4% were Black. A total of 2,070 (35.6%) participants had at least one pre-existing comorbidity (defined as a BMI ≥30 kg/m2, cardiovascular disorder, respiratory disease or diabetes). The median follow-up time post-dose 1 and post-dose 2 was 132 days and 63 days, respectively.
A total of 131 participants had SARS CoV 2 virologically confirmed (by nucleic acid amplification tests) COVID-19 occurring ≥15 days post dose 2 with at least one COVID-19 symptom (objective fever (defined as ≥37.8°C), cough, shortness of breath, anosmia, or ageusia) and were without evidence of previous SARS CoV 2 infection. COVID-19 Vaccine AstraZeneca significantly decreased the incidence of COVID-19 compared to control
Following vaccination with COVID-19 Vaccine AstraZeneca, in participants who were seronegative at baseline, seroconversion (as measured by a ≥4 fold increase from baseline in S binding antibodies) was demonstrated in ≥98% of participants at 28 days after the first dose and >99% at 28 days after the second.
If you have one dose the antibody levels are 7,000-9,000 get a second dose and it jumps to 20,000-40,0000 with interval of few weeks to 3 months gap, if you have been infected the level jumps to 175,000
An immunological correlate of protection has not been established; therefore the level of immune response that provides protection against COVID-19 is unknown.
High seroconversion rates were observed in older adults (≥65 years) after the first (97.8%; N=136) and the second recommended dose (100.0%; N=111).
In participants with serological evidence of prior SARS CoV 2 infection at baseline (GMT=13,137.97 [N=29; 95% CI: 7,441.8; 23,194.1]), S antibody titres peaked 28 days after dose 1 (GMT=175,120.84 [N=28; 95% CI: 120,096.9; 255,354.8]).
If you were infected before you should get a rip roaring vaccine response
Spike specific T cell responses as measured by IFN ɣ enzyme-linked immunospot (ELISpot) assay were induced after a first dose of COVID-19 Vaccine AstraZeneca. These did not rise further after a second dose.
Now to the rubbish of the MHRA and the government’s advisory Joint Committee on Vaccinations and Immunisation They delivered a surprise by announcing approval of a regime that was not trialled. Sorry I have to say this is shambolic, as it makes a mockery of the whole regulatory process. Companies spend millions to do trials for 20 people on some committee to say wouldn’t it be fun to do this instead. I realise it is a National Emergency but I thought the MHRA is about safey and so to do something that has not been tested (for one agent) is rather against this principle….Shambolic.
Apparently both the Oxford vaccine and the Pfizer/BioNTech jab which is already in use will be given to people as one shot, followed by another up to 12 weeks later, in order to extend some protection to as many people as possible as quickly as possible.
Now if you have to wait until 12 weeks to get next dose it means reduced antibody levels for probably 8 weeks. Hopefully this is enough to stop you getting COVID-19/Severe COVID. The bean counters have come up with the view that this allows them to give more people their first dose. This is great but not sure why this approach has been applied to the BioNTech vaccine this was tested with an interval up to 6 weeks whereas information for the Oxford vaccine goes to over 25 weeks. Now the glass half empty view is that it stops people getting sick, but does not stop infection and means that the surving virus gets selected that is not inhibited by the vaccine and oops Ground hogday but thats not going to happen..Let’s hope
A nice low point to end the year on:-(
Thanks again MD for posting and trying to help those of us weighing up the options of whether and when to have the vaccine especially now given the lengthening of the dosing schedule.
As someone on Ocrevus/ocrelizumab, bit thrown by this post and, in particular, your last sentence (though thank you for highlighting it).
Does this mean: it is safe for those of us on Ocrevus to get the vaccine (be it the Pfizer or Oxford one)?
Does this also mean: it will not be effective until after we receive the second dose (12 weeks after)?
My understanding is that both vaccines are safe for those of us on ocrevus albeit our responses may be blunted. However, with the potential now of an up to 12 week interval between doses, timing our infusions around this will be challenging.
I’ve already posted about this so long story short. I’m due my next infusion on Tuesday and have been offered vaccination next Monday. I’ve decided having spoken to my MS nurse and the Staff Swabbing service (who are organising the vaccinations) to press on with my infusion and delay the vaccination until at least 6 weeks afterwards. This has mainly been driven by the uncertainty over when I’d get my 2nd vaccine and not wanting to delay my treatment by 18 weeks (to allow 6 weeks after my 2nd vaccine) Total nightmare tho I do understand the rationale behind wanting to give more people some immunity.
I have removed the sentence to avoid confusion.
1. In terms of safety I think when ever you have the vaccine it is going to be relatively safe, the issue of more concern is blunted efficacy. This may not be an actual problem as you may not need much of a response to get rid of COVID and remeber if it is the T cells and macrophages that are all important I am creating a mountain from a molehill.
2. In terms of efficacy. To get optimum protection you need both doses but you will get protection from one dose. I suspect the Oxford vaccine was planned to be one dose just like the ebola vaccine. The “experts” suggest that one dose is going to give you enough protection. This would mean you are protected or not hospitalised and so remove some of the strain from ProfK and co. I can understand the logic
3. But to address the comment “This is problematic for people on ocrellizmab…why did I write this”
The agents of most concern for vaccination are the anti CD20 antibodies as you continue to deplete the B cells and therefore we know that B cell vaccination responses are blunted when you vaccinate 3 months after ocrelizumab (Veloce) NCT02545868 Bar-Or et al. 2020. So the suggestion for rituximab by the British Association of Rheumatology WAS “Where clinically possible, the COVID-19 vaccine course should be given four weeks or more before rituximab”. Soon a 3-4 week dose you would have to give the vaccine 4 months after infusion One month for the vaccine and then 4 weeks to hope the B cells respond. Now this would mean you give the vaccine at 2 months after ocrelizumab and you know that this means the vaccine wont work well based on data. The ABN have yet to give advice as it is too slow
The pfizer bioNTech vaccine is supposed to be injection 1 injection 2 (3 weeks). If you go to the US label of ocrelizumab says “all immunizations should be administered according to immunization guidelines at least 4 weeks prior to initiating treatment with ocrelizumab for live or live-attenuated vaccines. When possible, non-live vaccines should be administered at least 2 weeks prior to treatment initiation”
So BioTech Inject Inject + three weeks wait 2-4 weeks and inject ocrelizumab (time = 5-7 weeks).
With the new suggestions this could be inject week 0 inject week 12 wait 2 weeks (time = 14-16 weeks)
If you are starting treatment with ocrelizumab it means you have to wait 4 months to start treatment rather than 1.5 months
If you wanted to delay your ocrelizumab to get a vaccine before the next infusion then you have to wait upto 4 months before the next infusion rather than 1.5-2months. Is this safe to wait so long? For most people I suspect the answer would be yes based on the phase II extension study (this is an opinion and I am not a neuro) where people went up to 12 months delay (i.e. 18 months after their last infusion). During COVId-19 ocrelizumab was delayed. How long was this in a recent paper the average was 2 months without a relapse and some people were up to 3 months.
One of our readers suggested a straddle start 6 weeks before and dose 6 weeks after…With the BiONTech we know a 1 dose strategy drops the effectiveness to about 50% from 90% (this is based on small numbers and does not account for benefit with time so this may go up to 80%). For the Oxford vaccine we know the T cells are generated by one dose and they were not boosted by the second dose. However the antibody responses were boosted and the longer you waited between doses the higher the antibody response seemed to be.
As you can see there is no magic formula about the vaccinations look at hepatitis B vaccine it is 3 shots and if you are like me then I did not seroconvert and had to go round for another course before I converted. Therefore I suspect some poeple will need a top-up and so it will be good to have more than just two vaccines.
Anyway lets see what ProfG thinks….and remember the approval says that it does not have to be 12 weeks from first to second doses and the lower limit is 3-4 weeks. Maybe the bean counters will work this into their next computer model.
So 4 – 12 weeks fine for AZ vaccine (which is what most of us will be offered). Flexibility good for those on anti CD20 🙂
But agree Pfizer one should be 4 weeks, delay up to 12 unacceptable ☹
Love the comments:
Logistical constraints = cock up
Rip roaring response 😁
Here’s to 2021, Happy New Year to all xx
I wonder why ProfG yesterday recommended to wait 4 weeks for Ocrevus infusion after second dose of Biontech/Pfizer vaccine. According to the informations of the local health authorities and my neuro full protection is reached one week after second shot. What’s the reason for this deviation?
The label suggest 4 weeks or 2 at a push
Thanks and Happy New Year to all & thanks again for your very helpful blog
Agree with you on the Pfizer change. Although to be honest my expectations for the government and indeed the NHS are that low this doesn’t surprise me at all. Whilst I’m annoyed as this directly effects me (I was due the 2nd vaccine next week, and with my limpy immune system I really did want the evidence based approach). Perhaps the situation is actually that dire though, I’ve never seen Prof VT as sombre as he was yesterday.
Pragmatic question for you as an immunologist. (please prime your rose tintometer for the response). They seem to have extrapolated the AZ data onto the Pfizer vaccine. I wondered if fundamentally is the immune response to the AZ and Pfizer vaccine is similar? They are both delivering an attenuated spike protein which in theory should elicit a similar response, irrelevant of the exact delivery vehicle? Which would provide some justification for the decision to mirror the AZ dosing schedule for the Pfizer vaccine?
As an immunologist you are correct they are putting the ideas of one onto the other, however they are not the same beast. They have no clue who much of an immune response is needed to give protection. But I can see th Woolworths approach “Pick and mix” one vaccine here another one there. The RNA is gone in a couple of days whereas the adenovirus is not, it will be there for at least a week until the immune system gets rid of the chimpanzee virus. The 3 week of BioNTech is one week short than the Moderna so you can see the time difference is not exact. However the dog’s breakfast mix and match science (we will do what we can. The only go the Oxford data because they ploughed ahead when they didn’t have the supply of vaccine) seems to have infected regulation to become a beast of its own….using this logic all vaccines are the same so why are waiting for Sanofi/GSK vaccine, why not start using the Imperial RNA vaccine after all its an RNA too.
However I guess whats the point in griping the Government does what it wants…Face masks dont’ work (March), 1m safe distance, go on sking (Jan-Feb)/Summe (August)r holiday and you wont bring any viruses back
MD
This mentions spike specific T cell responses induced by the AZ vaccine.
Will the Pfizer one also induce T cell responses?
I am basically holding out all of my hope in my T cells as an anti CD20 customer!
Yes all vaccines do T cells as well
I had the covid jab, and was paralysed! I am 56. Should I have the 2and dose? Tell my consultant?:Andrea Woolf
I would say yes. You may want to take the second dose with prophylactic paracetamol and/or ibuprofen to prevent some of the deterioration due to a raised body temperature that vaccination is likely to cause.
I suspect that you may have had abit of a temperature, if you have demyelination abit of heat can block the nerves from firing. This is called Uhthoffs sign. Doctors used to put people in hot baths to induce this. I would tell your neuro