Wednesday, May 06, 2020

Vaccine futility

As some of you may know, your humble Devil studied (in a desultory way) Microbiology at university, and has always had a special interest in human pathogens. So, today I would like to talk about why a "permanent" vaccine for the novel coronavirus is pie in the sky; and cannot, as Boris keeps maintaining, be a pre-condition of removing the lockdown—not, at least, on a permanent basis.

The first point to make is that the novel coronavirus (nCV) is a single-stranded RNA virus (more about that in a moment) and we do not have an effective vaccine against any coronavirus.

Nor do we have, as some have claimed, a permanent vaccine against 'flu: what happens in that case is that predictions are made about what 'flu variants are likely in that year, and then people are given a jab that aims to cover all of them. Sometimes this works (e.g. UK 'flu deaths in 2018/19 were circa 1,700); sometimes the predictions are wrong, or a new strain emerges, that is sufficiently different that the vaccine is largely ineffective, and deaths soar (e.g. UK 'flu deaths in 2014/15 were in excess of 28,300) [Source for both figures.]

To start with, let's sketch, at a fairly high level, why this should be.

High mutation rates


The first issue to address is why single-stranded RNA viruses mutate so quickly...
  • advanced cells (such as in humans) reproduce using DNA which, as we all know (right?), is a tightly wound, highly-stable, double-stranded helix;
  • when the cell reproduces, the DNA helix unwinds and cell machinery moves along the strand to duplicate it;
  • the second DNA strand is then used to check and validate that the original one has been duplicated correctly;
  • this validation step is why DNA-driven cells mutate incredibly rarely.
In a single-stranded RNA virus, not only is RNA less stable than DNA, there is no second strand—and thus no validation mechanism: this leads to far more transcription errors on replication, i.e. a far higher mutation rate.

Given that viruses replicate many millions of times, then one can see that mutations will happen pretty frequently. As we can already see in the new coronavirus...
Researchers in the US and UK have identified hundreds of mutations to the virus which causes the disease Covid-19.

But none has yet established what this will mean for virus spread in the population and for how effective a vaccine might be.
So, why would these mutations matter?

Antigens and antibodies


Again, very broadly speaking, human cells are not smooth: they are studded with structures that enables resources to be attached to, and absorbed into, them—vitamins, minerals, oxygen, enzymes, etc. Pathogens, including the coronavirus, attach onto one or more of these structures in order to pass into the cell.

In order to do this, viruses develop their own structures—in the case of coronaviruses, these are the S-spike structures that give them their name—which act as the "key" to let them into the cell. These "keys" are known as "antigens".

When combating pathogens, your body manufactures "antibodies": these bind to the pathogens antigens and they are highly specific. If the shape of the virus antigen changes in any significant way, then the existing antibodies will no longer work—and your body has to start all over again.

How vaccines work


A vaccine works by introducing a something that looks exactly like the virus, but does not do the same damage, into the body. The "shell" has the viral antigens, but the dangerous bit—the RNA—is damaged, disabled, removed or otherwise "attenuated". The body then recognises this fake virus as a foreign invader, reads its antigens, and builds antibodies that will attack anything that looks like it—all without you getting ill.

(Actually, whether or not you have a likelihood of getting ill or not rather depends on whether the virus uses negative-sense or positive-sense RNA—there is a higher likelihood of illness with a positive-sense RNA virus vaccine, such as nCV (influenza viruses are negative-sense)—but I am not going to get into that just now.)

However, if the viral antigens have mutated significantly enough that the existing antibodies do not recognise it, but little enough that the antigen can still grant it access to the cell, the vaccine will no longer work.

Summarising the problem


So, with sufficient changes in antigens, the vaccine-generated antibodies will not work, and those infected will suffer the ill-effects of the virus (many of which are actually caused by your body's reaction—particularly dangerous, and often fatal (particularly in COVID-19 patients), is a "cytokine storm").

Viruses with a high mutation rate (particularly single-stranded RNA viruses) tend to lead to a vast number of significant changes in antigens—rendering vaccines temporary at best, as with 'flu.

Coronavirus is a single-stranded RNA virus—so no vaccine is going to be permanent.

What now


As such, this new variant will be with us for a very long time—will we shut down for weeks every time that it comes back around? Well...

In my next post, I shall discuss various treatment pathways. But, please, do not think that "a vaccine" is going to be the way out of this mess—and if Boris and co start to make that a condition of lifting lockdown, call them out on it.

They are either dangerously ignorant, or lying. So, no change there then.

1 comment:

Anomalous Cowshed said...

On mutation rates;

There'll be a certain finite number of ways, permutations or combinations, in which the "new" replicated virus can mutate.

It does strike me that some number of those ways, possibly very many of them, will effectively render the new copy inoperable, or make it less infectious or less lethal.

So, there's some level of probability that the virus simply randomly mutates itself into much less of a problem over time.

The reverse must also be true; there are some ways that the mutation can become more infectious or more lethal.

Not exactly the best way of dealing with the thing, but which has the higher probability?

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