Despite the relaxing of the lockdown measures, many people are still too scared to go to restaurants/travel on the Tube/go by plane/hug their family. The most common aspiration is that the introduction of a successful vaccine will lift all these worries. How near are we to achieving that aspiration? On Tuesday I attended a webinar given by Professor Andrew Pollard, Director of the Oxford Vaccine Group, who gave an update on CoVid vaccines in general and the Oxford vaccine in particular. These are my conclusions based on what he said, and what I’ve read subsequently.
How many vaccines are being tested?
This is an easy one, in addition to the Oxford vaccine, there are 22 other vaccines worldwide that are being tested in humans and a further 140 being tested in animals.
How do the vaccines work?
Many (including the Oxford vaccine but not all) work on finding a harmless way of introducing the spikey bit of the CoVid virus into the body, which will generate an antibody response. (It is the spikey bit that causes the problems – as this allows the virus to attach itself to all types of cells and tissues within our bodies.) Thus, when faced with the real CoVid virus, the body will generate antibodies against its spikey bits and neutralise it. What the Oxford group are doing is to apply some fancy genetics and incorporate the genetic code to produce the spikey bit into a harmless virus. The vaccine is this genetically modified virus. Other vaccine laboratories are finding different ways of producing antibodies.
Is it safe?
That is obviously the most important question. Of course, all vaccines are tested in animals but that doesn’t guarantee safety in humans. The first stage of the Oxford clinical programme is to test for its safety in humans. My guess is that the results of that will be published very soon (ie a few weeks). (See below for stop press on results from the USA vaccine). I also guess that if there had been a major safety concern with the volunteers who have already participated, and who are being closely monitored, that would have become apparent. Whether there are longer term hazards from the vaccine can only be determined by long term studies!
Assessing an antibody response?
The result of whether there is an antibody response in the human volunteers will emerge at the same time as the safety information mentioned above. What will be important is to know not only what proportion of the population are likely to have an antibody response, but also what is the size of this response (ie are ‘enough’ antibodies produced) and is it possible to predict who will, and who will not achieve, an adequate response.
One concern is that those most at risk from the complications of the infection are the elderly and as we age the response to vaccines diminishes. In the second phase of the Oxford programme the vaccine is being tested in people aged over 55 and those results will come a little later.
If there is an antibody response does that mean protection against infection?
That is a more challenging question and one that will be determined by the larger trials Oxford (and others) are carrying out in the UK and worldwide. In order to quantify how successful the vaccine is in protecting against infection, these trials need also to discover what the infection rate would have been if people had not been vaccinated. To achieve this, a random half of the volunteers are given a safe vaccine (‘dummy’) that has no action against CoVid. The goal is that the rate of infection in people given the new vaccine is lower than in those treated with the ‘dummy’ vaccine.
Of course, the rate of infection may be even a lot lower than in the comparison group, but the public will be hoping for complete protection. Whether this is possible is not known. It may not be a fair comparison, but the annual flu immunisation may only reduce infection rates by 70%.
The other challenge for the researchers doing the trials is that if the rate of infection in the general population is very low, then there may be too few people developing the infection in the dummy vaccine group. It would then be very hard to show whether the active vaccine is effective. It is a paradox, but we need a high rate of infection in the general population to show the vaccine is successful. If the population are too successful at preventing community transmission of infection by measures such as distancing and face masks then it will be that much harder for the trials to show benefit!
One option, perhaps, could be considered for ‘high risk” groups, such as care home residents and health and care staff. As the vaccine is being produced anyway (see below), therefore assuming it is safe (at least in the short term) and it produces an antibody response, perhaps this would be enough evidence to justify starting a vaccination programme. This might be particularly for high risk groups and need not await the results of the larger trials to emerge. It would still be necessary to monitor the rates of infection.
How long would any protection last?
Again, this has to be studied and cannot be predicted with any certainty. Antibody response does wane over time; but this may not be a major concern. Vaccines work by producing an immune ‘memory’. Thus, if vaccination is successful, when faced with the real virus, the immune system ‘wakes up’ and start producing enough antibodies. This ‘wake up’ also stimulates a separate part of the immune system that produces cells to attack the virus
One theoretical concern is that the virus mutates and the vaccine, whilst effective against the ‘original’ virus, is not effective against any new version. This is why for example flu jabs need to be repeated each year against the new strain. Interestingly the consensus opinion is that the CoVid-19 virus does not mutate, or mutate sufficiently to be an issue.
If any vaccine is not completely protective or does not last, is there anything that can be done?
It is possible that giving two doses would achieve a stronger immune response, which is well known in other vaccines. Similarly, giving a booster vaccine, after some interval could also prevent waning immunity, again this is well known from other immunizations eg tetanus. I am sure studies on this will be started once we know we have a partially successful vaccine. What is also interesting is whether a “two-hit” policy might work. For example, if two vaccines, which have a different approach, but are both targeting the spikey bit, when given in combination that might produce a better response. The vaccine developers in Oxford and other places I know are in communication about this.
This all sounds like a long process when would the vaccine be available for widespread use.
Widely publicised is the linkup between Oxford and the drug company Astra Zeneca to produce possibly 400 million doses of vaccine for Europe by the end of 2020 and with other tie-ups 2 billion doses worldwide. The vaccine is thus being produced in these quantities in the expectation it will work. If we waited until the trials have reported their results to kick start the manufacturing process, then there would be significant delays. Most people would take the view that it is worth the financial risk.
OK so when can I be vaccinated?
We should all take note that it normally takes 5-10 years from the start of a research programme to develop a completely new vaccine. The CoVid vaccine research groups around the world are attempting to do this within a year. Even optimistically, this might still mean waiting several more months for a successful vaccination programme to be rolled out. Waiting several months for a successful vaccine before returning to any kind of normality may be OK for some, but would be unacceptable for others – and for the economy – in areas with a very low risk of infection.
STOP PRESS
Interestingly a report published in the New England Journal of Medicine on 14 July of a study of the leading US Vaccine (Moderna Inc.), two doses of their vaccine, 28 days apart, produced a successful antibody response in 45 patients, although there were some with side effects.
Making sense of CoVid-19 with Silman 