If we were to find ourselves in the middle of a 'deadly viral pandemic' with no likelihood of a vaccine for years, if at all, what shall we do? Should we lock-down our societies, institute mask mandates and social distancing (along with all the other measures) on an ad hoc basis, whenever we feel that we at some arbitrarily imposed threshold and then hunker down and wait for the miracle cure? Or try to retain some semblance of normality whilst pursuing differing solutions, simultaneously? Well, we all know the answer to that one, but how about this; why is the first instinct of our elders and betters to think of a miracle cure at all?
We could give them the benefit of the doubt (again) and concede that they were perhaps panicked into a response. We could agree that it was worth taking the precaution of locking down for a short time until they got a handle on what they were dealing with. However, we might, if we were sticklers, expect that governments with access to the best experts in their respective countries, might have swiftly assessed the situation, understood the history of coronavirus infections and then made sensible decisions, balancing risk and reward.
Because it is well known that viruses mutate over time, due to unfaithful or faulty replication of their genetic code. Different viruses mutate at different rates; coronaviruses are middle of the road, speed wise. Over time, the variants that survive are the ones that don't cause the population to self isolate, as those variants that do are far more likely to die out.
So, attenuation (the gradual loss of intensity) is achieved by benign variants spreading and the more harmful kind fizzling out (Spanish flu). This is why a virus may initially have a relatively high sickness/mortality rate before it becomes less serious and a greater proportion of the population present as asymptomatic. None of the above information is revelatory to the experts in the field.
In the specific case of Covid 19, nature has surpassed herself. A study from July 2020 demonstrated that the immune system has been fighting back strongly, attenuating the virus at a much faster rate than expected.(1) This is due to an active defense system, already existing in our cells (pre existing T cell immunity). The attenuation is done by altering the genetic code, slowing down its replication, making it less stable and even enabling the body to fight it without producing neutralizing antibodies.
A vaccine is not the only way to deal with Covid 19 and it never has been. One sensible strategy, instead of betting everything on a vaccine, would have been to see if any existing drugs could be repurposed and whether there were any natural compounds that could ameliorate the virus. Re-purposing drugs is an industry within an industry already, and as a number of the drugs in question are no longer protected by patent, it's a more altruistic endeavor than the headlong pursuit of a new vaccine. Indeed, one might hope that 'saving lives', the constant mantra to which we are subjected, is more important than profit.
Re-purposing has not happened to any great extent, at least not in the west. In other parts of the world, several drugs and vitamins have been used to great effect, but efforts to draw attention to the efficacy of hydroxychloroquine, ivermectin or even the more humble minerals, Vitamin D and Zinc, have met with much resistance and claims of insufficient clinical evidence, which is richly ironic when one examines the paucity of evidence accumulated during the vaccine clinical trials.
That argument will be pursued in other articles. For now, it is enough that active obstruction was offered to the idea of using existing drugs as prophylactics and/or early treatment. The concept of allowing herd immunity also met an untimely end, as the risk was deemed too high, seemingly by the ‘experts’ in the press. So any faith in the extraordinary adaptive power of the immune system was rejected out of hand and it was decided that human ingenuity would have to be the answer.
It didn't publicly occur to the scientists that, by vaccinating against one strain of the virus, selection pressure would be applied to other resistant strains, allowing them to proliferate and that these mutations, if they occurred on particular parts of the viral DNA, might render the vaccines impotent. In this context, the World Health Organisation's stated aim of eradicating the virus and its comparison with smallpox, a virus that killed 30% of the people it infected, was asinine.(2)
Traditional vaccines seek to head the virus off at the pass, not allowing it to gain a foothold in the body, by producing antibodies. There are four main types; an inactive vaccine that uses the dead virus (such as for flu or rabies), an attenuated virus which uses a weakened version of the live virus (measles, mumps and rubella), a recombinant vaccine which vigorously target key parts of the virus (HIV, hepatitis B) and toxoid vaccines, which accomplish much the same thing in a slightly different way (diphtheria, tetanus). So, which type would be most suitable for Covid? Answer; none of the above.
Previous vaccine attempts
The effort to produce a successful coronavirus vaccine has a long and sorry history, Attempts were made to produce a vaccine for SARS-COV after the outbreak of 2003 and vaccine trials were conducted on mice and ferrets.
The vaccines, of a traditional form, included portions of the virus spike protein, in order to target the same portion on the virus itself (which, incidentally, is the part of the virus targeted by the new mRNA vaccines). This is a part of the virus that is shaped like a spike, hence the name, and which binds to human cells. And it was here that problems were encountered.
The animals were given the vaccine (which worked well, initially) and then, 28 days or more later, were challenged with the live virus. This was not a success. The lungs of the mice were badly damaged by tissue inflammation and the immune system response was 'shoddy', inasmuch as the unvaccinated control group fared far better than the vaccinated group.(3) All of the animals were badly injured and some died.(4)
The same problem was encountered in vaccine development for the Middle Eastern Respiratory Syndrome (MERS).(5) There are two causes of these results: pathogenic priming or Antibody Dependent Enhancement (ADE) and, you guessed it, allergic inflammation. And this problem is not new – vaccines for Dengue Fever and coronaviruses have been researched since the 1960s and this backfiring immune response has long been noted.(6)
The pathogenic priming phenomenon has also been found with HIV, influenza and SARS and has thusfar been most observable in Dengue Fever, where there are four main strands (serotypes) of the virus. It has been shown that people who have previously been infected with one strain of the virus, if subsequently infected with another, are 15-80 times more likely to experience a severe response. The antibodies, instead of neutralising, enhance uptake of the virus.(7)
The specifics of pathogenic priming
For a vaccine to work, it has to stimulate our immune system into producing a neutralising antibody, which binds to the virus and neutralizes it. A non neutralising antibody, on the other hand, is one that fails to do its job. Reasons for a non neutralising antibody:
Binds to the wrong part of the virus
Binds too weakly
Weakens over time
Transitions from a neutralising antibody to a non neutralising one when it encounters a different strain of the virus.
In SARS, the theory is as follows; the non neutralising antibody, which is still binding to the virus, can direct the virus to enter and infect your immune cells and, thereby, replicate rapidly causing what is termed a cykotine storm, where the immune system allows the virus to infect other parts of the body. Basically, the non neutralising antibody enables the virus to use the immune system against you.
In effect, despite (or rather, because of) the vaccine, the immune system produces an antibody which is or becomes ineffective and when the system is actually challenged by the live virus, the infection is much worse than if there had been no initial vaccination. It doesn't happen on all strains of any given virus; it depends where on the DNA strand the mutation (which has created the new strain) has taken place.
This problem exists in coronaviruses in general and SARS related viruses in particular and it has not been solved with the use of traditional vaccines. And it's important to note that, because of the failure of animal trials, vaccines were not allowed to progress to human trials...until now.
While less is currently known about SARS-COV-2, the similarities with other coronaviruses are sufficient to suggest that this risk is real. A successful vaccine, therefore, has three challenges to overcome:
Circumvent the basic ADE problem for SARS-COV-2
Prove that subsequent strains of the virus do not induce it
Prove that other coronaviruses do not induce it (i.e. the common cold).
Is there a way to test whether these potential problems have been overcome? Well, not in animal testing as even our closest relatives, primates, cannot exactly replicate the process that would occur in humans. And it's unethical to test in humans, apparently.
Observations
A major trigger for ADE is viral mutation, particularly in the spike protein part of the virus, which is a process that naturally occurs in coronaviruses. An antibody that was neutralising can, therefore, become non neutralising. Further, as future strains and their make-up cannot be predicted, it is impossible to know whether ADE may subsequently become a problem, even it isn’t currently. This is not something that will be seen for several years – the virus needs to be given time to mutate. So, ironically, any vaccine could make the virus more pathogenic, not less.
Additionally, there seems to be a large difference between a virus primed immune system and a vaccine primed immune system. A natural antibody reaction is a much more complete response to the virus, recognizing and neutralising many more portions of the virus and keeping non neutralising antibodies to a minimum. In addition, T cell responses are comprehensive and across the board.(8)
With most vaccines, only a portion of the virus is targeted and neutralised and the larger range of T cell responses is absent, thus making the vaccine a more limited solution and increasing the possibility that there will be spare, non neutralising antibodies in play.
In an ideal world, or even in this world, a traditional vaccine would be trialed for 5-10 years, to test for possible side effects. And when the vaccines which are being used for Covid are not traditional vaccines, having have never been administered to humans before?
This must add another layer of uncertainty. Not only are the new vaccines targeting the same part of the virus that was unsuccessfully targeted in previous trials, they are doing so via a method that is unprecedented. You would think, would you not, that an excess of caution would be called for? The sort of approach that has been invoked to lock us down; but, no.
Have the problems with coronavirus vaccines and ADE, not to mention the additional adverse inflammatory response, been solved? If they have, where is the evidence? It may be that, despite all these reservations, it all works out fine; that the mRNA vaccines are a triumph and, ten years down the line, there are no downsides. Would that justify the gamble that is being taken in the here and now?
Citations
Rice, et al Evidence For Strong Mutation Toward And Selection Against U Content In SARS-COV-2: Implications For Vaccine Design, July 2020
Deming Damon, et al Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants, 2006
Chien-Te Tseng, et al Immunisation With SARS Coronavirus Vaccines Leads To Pulmonary Immunopathology On Challenge With SARS Virus, 2012
Anurodh Shankar Agrawal, et al Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus HUMAN VACCINES & IMMUNOTHERAPEUTICS 2016, VOL. 12, NO. 9, 2351–2356 http://dx.doi.org/10.1080/21645515.2016.1177688
as per (3) above
Halstead S.B., Immune Enhancement of Viral Infection, Prog. Allergy 31, 301-364 (1982)
Zhi-yong Yang, et al Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses, 2004