Viruses could bury your life:
Many of us are just now realising that the Covid-19 contagion may have upended our familiar ways of life for a lot longer than we thought it would. Maybe forever. And while the Corona virus may not kill too many of us at all, the real or imagined threat of this and future pandemics may get to bury many of our prized freedoms for good. Unless scientists find an effective vaccine fast.
The good news is that the worlds’ drug companies and legions of researchers are all working feverishly to win a highly-competitive and urgent vaccine development race. The stakes for humankind are high. The commercial and social prizes for the winners are big. Even so, the chances of anyone discovering an effective vaccine anytime soon is slim.
Successful vaccines have been developed in the past. Today Measles, Polio and even the Flu are no longer the deadly threats to life they were then. Today, a vaccine guards us against Rabies deadly 100% mortality rate. So, the mission to discover a vaccine for this contagion has a shot. But each of the successful vaccines took a long time to find. And some had disastrous results such as RSV (Respiratory Syncytial Virus) in the USA and Dengue in the Philippines. But many diseases such as HIV and SARS (a Corona virus) are still without a vaccine.
The human herd also builds up immunity naturally and sometimes quite quickly. There are already mumblings in scientific circles that suggest we may we well down that track. It is quite possible that our own immune systems respond adequately to the virus in time and a vaccine becomes less relevant to returning to normal.
How to make a vaccine:
A virus, which can only be seen through an extremely powerful electron microscope, consists of both highly toxic and less toxic parts. To create a safe vaccine, scientists must distinguish the less toxic elements of the virus that can be usefully used to help the body trigger the antibodies needed to win. Without overwhelming its defences. Or triggering the wrong ones. This complex process involves a meticulous and systemic trial-and-error testing routine to discover which parts are which. Not unlike defusing a live bomb. Except this exercise requires the isolation of vastly more variables. Blindfolded. And the consequences of error are much more deadly.
The complex process roughly follows the following 8-step sequence:
- Find some survivors of the illness.
- Identify the antibodies in the survivors.
- Produce a reliable test for these antibodies.
- Work out which part of the virus is least toxic.
- 3D model the virus and antibody to see where antibodies will attach.
- Find a way to cleave the desired portion off the body of a living virus.
- Find a way to grow large quantities of the virus as well as develop a way to manufacture lots of the selected candidate.
- Purify and check for stability at room temperature for transport and storage.
THIS WILL BE THE VACCINE.
This is the scientific part of the process and is the quick part. There may be many sites to attach an antibody to, so different companies all over the world are trying different sites.
Now to test it: (This is the part that will take the most time)
- Inject sequentially higher doses into a series of primates and ferrets, starting at a billion and go up to a trillion copies per injection.
- Wait three weeks to check for disease and toxicity and measure whether they have formed the antibodies we want.
- Based on the above, we select a group of paid volunteers (20-100) to test the initial dose. A current group from Oxford are receiving a range from 5 – 100 billion copies of the vaccine.
- Again, we now wait to establish the lowest dose that gives an appropriate measure of immunity; now we know the dose.
Testing for side effects:
- Now we select a bigger group (+/-1000) in a controlled environment (often prisoner or soldier volunteers), and inject the dose.
- We wait for the immune response and then challenge half of them with an infectious dose of Corona virus.
- We monitor the response of all triallists and wait several months before re-challenging them with a Corona dose. Hopefully the re-challenge proves immunity.
- Should the side effects be tolerable and the vaccine works, we now inject it into a much larger group who may have concomitant illness such as diabetes, heart and lung problems, or obesity in order to establish unusual reactions.
Remember that this injection is a living part of a virus. Children and pregnant women are the last to be tested. At this stage a larger group (several thousand) may be used as a trial test in the general population. The difference being that they will not be intentionally exposed to Corona subsequently. They will however be monitored for antibodies and reaction to Corona in the community.
In the meantime, laboratories are developing ways to produce industrial quantities of the virus particles. As the months progress, immunity will be measured to see if booster injections are required to maintain immunity. Any failure on this path means going back to the drawing board.
You now understand why the above process can’t be fast tracked and although at optimum conditions may be as short as 18 months, responsible companies won’t promise results before five years. The Chinese presented the complete genome to the West when the epidemic broke in early January, which has helped accelerated the development of the vaccine.
Other techniques: (Two of many)
- There is a technique called the Vaccine Rapid Response Platform, where you inject part of the virus’ genetic code into the body. This is taken up by your cells and it stimulates you to make virus parts that will induce an immune response. This technique can bypass several steps in the above manufacturing process. This type of vaccine has never been done in humans before, but is currently being appraised as an option.
- Another technique is to modify the virus – making a sick version of it so that it can’t replicate as rapidly as an aggressive strain would. This new modified strain is injected into the body as a weak infection, that presents a mild illness with the capability of forming antibodies while it slowly multiplies.
Over 35 current candidates, many already in human trials:
I understand that there are at least 10 projects quite far down the line, but the clinical testing will take up most of the time going forward. Luckily many different sites have been identified and are independently being tested at the same time, so we don’t have to put up with a trial-and-error delay.
Vaccine side effects are recorded by a central body in perpetuity, as a check against spurious claims such as Autism.
What can go wrong?
Responsible companies in the past claim that it cannot be done in less than 26 months, however the newer techniques may make it shorter. The human testing is what is critical here. Note that the quest for an HIV/Aids vaccine has failed despite 37 years of intense research, and we don’t have a vaccination for all strains of flu. Of significance is the fact that the SARS virus (also a Corona virus) scare 17 years ago has not resulted in a successful vaccine against it.
If inadequately tested, exposure to the wild virus may result in an inappropriately strong response much like the so-called Cytokine Storm, where we hear about antibody immune enhancement. One example of this is when an inadequately tested Dengue vaccine, manufactured in France, resulted in over 600 children dying when eventually exposed to the wild virus. This sent doctors to jail. In the USA, Trump has dangerously allowed companies to bypass animal testing before the human phase in order to be the first one to win the race and multibillion dollars in profits! It may pay to wait a bit longer for a properly tested vaccine.
Hope for the future?
Vaccines have saved millions of lives and prevented debilitating illness such as paralysis from Polio. Covid-19 with its low mortality rate and negligible permanent complications has given scientists breathing space to come up with a medical solution.
This highly infectious virus, however, may help us to both win and lose: overwhelming us and creating a herd immunity before a vaccine is developed. If it self-destructs due to its high infectiveness, the world will become immune to it anyway. In which case, all our efforts would have been in vain.
This virus is also known to mutate, so we may ultimately end up having a vaccine every year for a new different strain of the virus, much like we don’t have a flu vac for every strain of flu. (Conspiracy says that big Pharma can do this for flu, but it would be much less profitable to have only one flu vaccination in your lifetime).
Sticking my neck out: I don’t think that we will develop a viable vaccine for this and future strains that will be safe for at least five years. However, I do believe that we will beat it through herd immunity. This will unfortunately result in government interventions and related restrictions on our lives for some time to come.
Time will tell. Perhaps history will reflect on our burgeoning populations, destroyed economies and altered freedoms and ask ‘What was that all about?’. Human panic may turn out to be the real disease we need to vaccine more urgently.
Dr Mark Holliday.