Monday, 23 November 2020

Vaccines - what they are and how to choose them

SUMMARY

  • Like late buses, four vaccines have come along at once. 
  • The Moderna vaccine mRNA 1273, is as effective as Pfizer, and can be stored at -20degC. The Oxford Vaccine remains the most promising in practical terms. 
  • There are some caveats with studies - no peer review, light on detail, and small numbers..

  • Compulsion to have a vaccine is not needed with Sars-Cov-19. Group think is.

  • Why I will have the vaccine.
  • How are we going to choose?
  • Vaccines are a short term answer for a long term problem.


The Vaccines....

Fast on the heels of the Pfizer BioNtech vaccine with Sputnik5 in second place, two more vaccines have announced encouraging results with success rates again over 90%.

The Moderna vaccine, another mRNA vaccine with an effectiveness of 90% comes in third, and the Oxford's ChAdOx1 vaccines encouraging results are announced today.

Clearly these announcements are good news, at the very least because they are not bad news. Imagine if they were all quiet, suppressing the initial analyses due to poor results which allude to a vaccine being hard to create at all, or with low efficacy suggesting they might be, at best, the best of a bad job. 

Pfizer, Sputnik, Moderna, Oxford 
 - same destination, different price

The Moderna trial results of its vaccine, mRNA 1273, offers a bit more detail than those from Pfizer, and suggests prevention of disease as well as infection. All 11 people in its trial who went on to develop severe COVID19 were in the placebo arm. 42% of their volunteers also were deemed to be at risk of severe COVID19 which helps.

Pfizer have now submitted their vaccine, BTN162b2 to the FDA for authorisation following the trial reaching its target of 170 confirmed cases. There have been no concerns regarding safety after a follow up of two months after vaccination. It is also reported to be 94% effective in the over 65 age group.

The results showed that 162 of the COVID19 cases were in the placebo arm as well as 9 of the 10 cases of severe disease. This makes the vaccine 95% effective. With no safety concerns raised in the trial, approval is almost assumed and the vaccine should be available by the end of this year with health staff and front line staff a priority. 

Incredibly, they plan to produce 50 million doses by the end of this year and 1.3 billion by the end of 2021. They might be expensive right now, but they are easier to scale up than the more traditional vaccines. So the mRNA vaccines applications for approval are now on the desks of the regulatory authorities in the US, EU and the UK.

Oxford have just announced their interim phase 3 results from their ChAdOx1 vaccine. Of 20,000 volunteers, there were 131 cases of COVID19 - 30 in the vaccine group, 101 in the control, giving an impressive (in normal times) effectiveness of 70%. When a low dose was followed by the normal dose, effectiveness rose to 90%. In the intriguing world of immunology, less can seem more. 

Oxford

When complete, the trial will involve 60,000 people from all over the world, in all age and ethnic groups and will report in full be the end of the year. It seems their vaccine could prevent transmission as there were less asymptomatic infections in the vaccine group too.

The have submitted their results for peer review and applied for regulatory approval. In the meantime large scale manufacturing is ongoing in ten countries to ensure access across the globe. 

Their vaccine uses technology involving what is called a vector. That is, using a harmless virus to stimulate our immune response. 

It's novel technology too in that the adenovirus carrier has been engineered specifically for its purpose. 20% of its genetic material has been removed to prevent it replicating, and genes inserted which carry instructions to make spike protein. When inside our cells, this information is transcribed and so again we make spike protein. Our immune cells recognise it a foreign, destroy it and remember the spike proteins when we come across the real infection. 

When it comes to storage issues, it has clearly streaked into the lead. Further, its partnership with AstraZeneca is based on distributing the vaccine on a not-for-profit basis for the duration of the pandemic and for perpetuity for low and middle income nations. This too would be ground breaking. 

Storage issues

The Moderna vaccine has another big advantage over the Pfizer version as it needs storage at -20 rather that Pfizers -70 degC. That makes distribution a whole lot easier, though the price tag of £50 for Moderna's two shots (£30 for Pfizers) will be a different disadvantage, and disappointing when considering how much public money went into its development.  Both will also have very high distribution and storage costs, more so for Pfizer.

So storage is really important. It's one thing having a carefully conducted trial with lots of resources poured into the care needed it getting it right. It's another thing distributing vaccine safely around the world so they are at their best when infected or inhaled. The Oxford and Sputnik vaccines definitely are more likely to be effective at the end of their far less complex "cold chain" of distribution. 

However, when it comes to practicality, the Oxford vaccine can be stored in standard fridges here and around the world. This must give it the edge in practical as well as in economic terms. (£2.23 a dose)

Caveats.

However optimistic things seem on the vaccine front right now, a few points need making. 

First, the news is being made by company announcements rather that via journals with peer-reviewed scientific scrutiny, and so have not been "fact checked" in the normal way. It would have been better for the drug companies to have waited, and indeed for governments to have waited too, until things are more certain in terms of oversight and indeed, waiting for further and more full results. It need not have taken long. 

As pointed out in Private Eye, immediately after the announcement, the Chief Executive officer of Pfizer, sold some of his shares in his own company and profited from the news to the tune of £5.6m. Share price increased by 20% after the announcement.

Pfizer share price

The Chairman of the company should have had a word in his ear, only its the same person occupying both roles! The jump in share price was due to the company's own announcement which seems just the sort of practice that earns drug companies a bad name, even though 'normal' executive behaviour. I wonder also, why they thought this was the best time to sell? Perhaps he knew that the Moderna vaccine might have an edge in terms of mRNA vaccine storage?

Secondly, money matters.  The Oxford ChAdOx1 vaccine is cheap, easy to transport and may well be just as effective as the mRNA vaccines. Their earlier results showed encouraging benefits in the elderly, and have just been published in the Lancet in full. Importantly, the vaccine generates adequate antibody and T Cell response in the elderly where the need is most. That is the best way to get this information into the public domain rather than 'science by media".  Remember Gilead's announcements of the success of Remdesivir? In the real world it failed to live up to the company's hype. 

Finally big conclusions are being made on the basis of small numbers.  We also know from drug trials that medicines usually perform less well in the real world, where conditions are very different from those in a carefully conducted trial. Ultimate effectiveness will be determined in the real world.

Buy British?

The UK government has already ordered 40 million doses of the Pfizer (£1.2billion) and now 10 million from Moderna (£500million) to add to the 100 million doses of the Oxford vaccine, (£223million) in what reminds me of the January sales without the discounts. Including other pre-orders, we will have theoretical access to 335 million doses of vaccine, and thus an ability to vaccinate everyone in the UK nearly three times over. I assume we will not be taking up all of our pre-orders as time goes on?

The Oxford vaccine will be made in the UK which will avoid the chaos of ordering Pfizer's vaccine from EU nations, particularly if BoJo gets his way with a no deal Brexit. Again, the Oxford vaccine is on offer for £2.23 a dose with discounts possible as we have already invested in its development. With the chancellor already hitting public sector workers with pay cuts, cost matters. 

Perhaps the mRNA vaccines could be used this winter for front line staff and care workers, and then the Oxford vaccine used in the same way as flu for the rest of us in the vulnerable groups. Perhaps the Oxford vaccine for everyone? Some of these decisions will be made centrally. 

It seems to me that the case for expensive vaccines with big storage and transport problems has to yet to be made in the face of cheaper alternatives. There are the special cases of those on medicines which affect immunity and people who are immunocompromised. The mRNA vaccines might offer an advantage there, but those decisions will be very precise for the individual concerned. 

Another fear is the thought of vaccination being compulsory..... 

Compulsion

Fears regarding making the vaccine mandatory have fuelled the anti vaccination community whose concerns need to be countered with science and fact. They are concerned about the restricted freedoms of those who choose not to take up the vaccine. Of course if you want to travel to the US or Australia where vaccination is already mandatory, then you will need the vaccine before you go, so this is clearly already happening abroad. However, to make it mandatory here (or anywhere in my opinion) is not based on good science or politics.

Indeed, David Nabarro, the WHO's special envoy for COVID19 agrees. To quote him: "I am against being mandatory on most things because I think in the end we want people to do the right thing in the right place at the right time, because that is what they want to do"

Further the Public Health Act (1984) and the Coronavirus Act 2020 both state that compulsion is against the law. The law of course, can be changed, but the politicians would have an impossible task in getting this done as it is morally unsound and even many Conservatives would find it impossible to vote for.

In the EU there is no difference in vaccine uptake between mandatory and non-mandatory systems, so there are arguments that compulsion doesnt work. 

I hope the vaccination programme will protect those at risk of infection at work or at home, then those vulnerable to the illness, then those who want to have it, rather like flu, and it should stop there. This would solve most of the problems COVID19 is causing, particularly in terms of hospital admissions, and the availability high dependency and intensive care beds and the staff they need.  

We need informed consent for this as with any other treatment, and we have to accept that everyone will not seek protection. However we feel about our own individual situation, "Group think" however, does apply...

Group Think...


The involved making the best decision, based not only on what is best for us, but also what is best for our families, those around us at work and the wider community  For instance, when I was a partner with other GP's we all agreed to have flu vaccines annually as it seemed unfair for any one of us to risk being off ill with flu and thus leaving our colleagues to cope at a time of most pressure. One for all and all for one sort of thing. 

If the pandemic had a higher mortality rate this might be different. We all need to consider our role as members of our groups as our decision will impact on others too. 

There is a question of how any community of people would feel if there were reluctant 'super-spreaders' who didn't like the idea of vaccines set against vaccination against an illness like SARS with a mortality rate of 10%, one hundred times more deadly that COVID19. Thankfully that is not an issue right now. 

Why I will have the vaccine.

Once it is approved by the MHRA in the UK, I shall have a vaccine. 

This works both ways
Of course, a big reason is that I would like to have antibodies and T cells around when I meet Sars-Cov-2. I cant develop complications if I don't get the infection. Evidence of reduction in infectivity and transmission will hopefully not be too long in coming and will certainly arrive by the time vaccines become widely available for people like me. Oxford already seem confident that the vaccine means less transmission.

While keen to change the world, seeing friends and family without concerns regarding infection or restrictions would be a wonderful thing. Then the fight for a better world must be engaged with the lessons of COVID19 learned and put into action. Ideally. 

There is a wider element of morality not prominent in the arguments used against vaccines. We are all a tiny part of the population and it is hoped, though too early to say with confidence, that having the vaccine will prevent me from passing it on to others. 

This applies to anyone caring for, married to, or in contact with those who are vulnerable to COVID19. With 10 million or more people in the vulnerable group, this is a big chunk of the population. Include those who have elderly relatives, friends at risk, people of colour and the deprived and the numbers climb. 

In this crowded world of pandemics, I feel very positive about vaccination, though not compulsion. 

Which one?

For many of us this will be an individual choice, which is why we all need to learn a little more about vaccines, I hope this post helps a little. I will explain how the vaccines work in my nest post. 

I like the idea of the mRNA vaccines and they do seem to represent the future of vaccination, particularly against Ebola, other haemorrhagic diseases, Dengue fever, any re-emergence of the tragedy of Zika and the many other emerging infections diseases lurking just beneath the surface. 

Right now they are expensive and have big problems with transport, the tab for which will be met from the public purse. Most of us don't have to decide right now, but if I was in close contact with lots of people, like front line staff, I might be in the queue for an early mRNA vaccine if it became available first. 

Choice, choice??

For people who are immunocompromised the mRNA vaccine also looks a safer bet, though anyone with medical problems will have to take specific advice as more details emerge.

Despite having MS I'm not immunocompromised as I have not needed treatment to manipulate my B cells away from damaging the myelin sheath of nerves, so I'm normal (in this respect). So  for me right now I'm veering to the Oxford vaccine. It is clever, cheap, easy to transport, can be easily integrated into vaccine programmes and storage technology as they stand in primary care. And I suppose, because they are made in this country and seem the most likely to address the global pandemic.

Im sure more information will be available soon and the race to get data peer reviewed and published, is running in parallel with regulatory approval and manufacture. 

A dogs dinner.

However successful the vaccines, humility is needed. 

The economic consequences of this are coming into view with the Rishi Sunak hinting at pay cuts for those very workers who kept his country going through the pandemic. His days as a popular, likeable chap might be coming to an end. The message that austerity was to blame for some of the deaths seems not to have been learned. No change there. Meanwhile big sums of public money have whizzed their way into the pockets of those who need and deserve it least. 

More imagination is needed with economic thinking. The time for a Universal Basic Income is now. Tax hikes are inevitable, they should be progressive and achieve a number of outcomes. The time for undeserved wealth is over. More on this later. 

It might be that Big Pharma and science will get out out of this mess, but Big Farmer and its corporations have got us into it. Poverty, and the consequent need for low quality cheap food is an economic as well as a health and environmental disaster.

A human disaster too!
And meanwhile, bats in caves, pigs in pens, and poultry in cages, all with immune systems damaged by our actions, are creating new viral strains, developing illnesses, dying off and creating the ideal conditions for the next pandemic. The next spillover event remains inevitable. 

Indeed, COVID19 is not the "big one" expected by experts in pandemics. That is likely to be an strain of influenza yet to arrive.

It might be that after this COVID experience, better surveillance, rapid isolation of spillover events, and immediate development of vaccines will mean that we are better prepared for the next pandemic. That involves thinking, international collaboration and spending.   We need a more effective WHO, well funded but without financial ties which currently make it so difficult to act with independence.

But it wont get us off the hook. Other effects of our global mismanagement, climate change, global heating, loss of space and species, pollution and globalisation of food will define the future of life on this planet, including bats, pigs, chickens, chimpanzees - and homo sapiens. 



1 comment:

  1. A good, clear exposition as always Colin. Thank you. You're right to highlight "the bigger picture - financing the vaccines and the overall background to new viruses affecting us. This will continue until the environmental and food-chain issues are sorted out. That's a LONG way off, unfortunately. Thanks again. Ian

    ReplyDelete

Thanks so much for your comment - I will get back to you shortly