'Vaccine Can Neutralise COVID Variant's Altered Spike Protein'

This strain appears to be more infectious than earlier strains of the virus and thus could be more dangerous. Most mutations will either be of no consequence or will be damaging to the virus, but it will constantly mutate and the worst would be if a mutation helps the virus evade the immune system of someone who had contracted the earlier strain of COVID-19, said Rakesh Mishra, director of the Centre for Cellular and Molecular Biology, Hyderabad. Thankfully, the new strain identified does not have such a characteristic, he said.

Mishra spoke to IndiaSpend about what the new variant of the COVID-19 virus means for the pandemic across the world and whether vaccines will continue to work against the new strain.

Edited excerpts:

Were we aware of or expecting such a mutation to emerge? Were we seeing mutations happening even in the last nine months?

Mutation in any living creature is a natural process and that is how living beings create variety, which is the subset for evolution. It is how things evolve. It is very natural that everything will generate mutations. Complex organisms do it more slowly because they have a "proofreading mechanism": If there is any error in copying the genetic material, it is corrected and therefore, the error is less. RNA viruses, on the other hand, do not have this proofreading mechanism. So they make lots of mistakes, which means more mutations are generated. That is why they are notorious and very difficult to control. The AIDS virus [HIV] and influenza virus (common flu) are examples. That is why we hardly find any vaccines or drugs against them.

The [novel] coronavirus or COVID-19 is also an RNA virus, which has a tendency to mutate and that is what it has been doing. The whole world is watching the genome variations that are emerging. So far, more than 400,000 genomes have been sequenced for this virus all over the world. Even in India, we have been sequencing, and in some 4,500 genomes that we have analysed, close to 5,000 mutations have been documented.

Most of the time, these mutations do not matter. We record them, they are of academic interest, we can trace from which lineage a person's infection has come. By doing this, we can figure out whether it is a reinfection. Most mutations would either be of no consequence or they may even be deleterious to the virus--they will either do nothing or the virus will simply be phased out because it will not be able to compete. But sometimes, when something becomes advantageous for the virus, that [mutation] will start to replace the existing one because [the new variant] is spreading fast. It is simply survival of the fittest. And that is what has happened with this new variant.

The new variant has many mutations, compared to the standard or other variants going around. Most importantly, what has changed is the amino acid in the part of the protein that reads the surface of the cell [of the body], through which it buys the ticket and enters the cells. And that mutation has made the handshake or the binding with the surface of human epithelial cells stronger. So it can catch faster while other variants can miss out--and therefore, not infect. If this [variant] reaches, the chances of infection increase.

There are other indications that it produces more virus [particles] also. So an infected person will shed more virus, and that also increases chances [of getting infected]. That is why it is interesting that within a couple of months, it has reached more than 60% of the infectivity in certain parts of the UK, from zero. That means it is going to take over and slowly, it will become the dominant strain or variant all over.

In the early days of COVID-19, many said the virus is also a living organism, that it is intelligent. Is this something that many of us laypeople are not grasping or fully understanding?

All organisms have ways of managing the environment and surviving, and so does this virus. The strength of this virus is that it is very infectious, which means it has managed to recognise the receptor of many cell types, particularly epithelial cells that make our respiratory system--outer surface of the respiratory tract through which air passes. Through air, it reaches and catches those cells using the receptor and enters. That is why it is very efficient in entering the cells.

Otherwise, viruses are kind of semi-living. Outside, they do not do anything. Unless they find the correct host, they will just lie and become inactive after sometime. For several hours--and sometimes days, in certain conditions--they will be alert and whenever an appropriate environment comes, they will infect and get inside the cells and make more copies of themselves. So we should not call the virus 'intelligent', but they are efficient and that is why they have been surviving and bothering us.

This mutation is efficient and said to have high infectivity, but may not be clinically or medically more dangerous. Explain to us what that means.

That is correct. What it is doing is it is catching the receptor more efficiently; it has stronger affinity for the receptor, [and] so it finds the cell. But once it enters the cell, it is like any other virus. The strength that it has matters only upto the entry point. After that, it is the same virus as the other variants. So clinical features, mortality, and therefore the response to vaccines remain unaltered. It does not really bother the rest of the process. The same treatment and the same care will be required.

With low infectivity conditions, some of us could have escaped; this one will not let us escape. That means the rate of infection will be much higher, given equal conditions like other variants. Therefore, although the treatment is the same, all of a sudden there may be crowding in hospitals because more and more people will come. Even if the percentage of mortality is the same, if a [higher] number of people get infected, the actual number of people dying will be far more.

You may have already heard that in a country like the US, hospitals are getting saturated--in California, [they are] 80-90% saturated. If more people get infected, that will be a disaster, because then we will not be able to provide care and save those who could have otherwise been saved.

For those who follow precautions--masks, sanitising and maintaining distance--would they be more likely to contract the new variant or is the probability the same?

The mechanism for the spread of the virus is just the same--that is, person to person. That is one big weapon we have against this virus, which some of us have been using and some have not: If you wear a mask, it does not matter. Its strength comes when it touches your epithelial cells. Let it not touch that. If we wear a mask, [practise] social distancing and [hand] hygiene, we can block this as efficiently as we are blocking other variants. So the tool to prevent this spread or defeat the new strength that this virus has gained is just a simple mask. That is why all we need to be is to be more alert and not let this virus sneak into the system.

Can you tell us how mutations could develop hereon? Could we have newer mutations that could be more dangerous? Could the pandemic remain with us for longer if a mutation that does not respond to the vaccine develops?

When we measured the mutation rate of the virus, it was slower than expected. It is mutating slower than the influenza [virus]. As I mentioned, every month you will have multiple mutations emerging, particularly when there are a large number of people infected. The virus then has more scope because of more numbers and in the same proportions, it will generate new mutations or new variants. And the fact that it [the new variant] has come after eight-nine months, in this duration, one mutation has managed to become more infectious, and therefore it is important for us.

Many months ago, we had identified a variant in India, A3I, which was a South East Asia-specific variant. At the time, although that variant was dominant in this part of the world (it was more than 40% of all cases at that time), we knew that its replication would not be as efficient, because there were certain mutations that gave us the indication. That little difference made that virus [strain] disappear. Now, all over India, we have the common variant, which we call A2A.

Mutations will happen constantly. Some or most of them will have either no consequence or negative consequence [for the virus] and they will disappear without our notice. But there will be mutations, rarely, that will provide advantages to this virus and the worst will be if the virus manages somehow to evade even the immune system that has seen another version of the virus earlier [that is, infect someone who had COVID-19 from an earlier strain]. Luckily, it has not happened this time. Most cases that are coming in are not of reinfection--[it is] very very rare [that] reinfection is seen. That means this virus is still respecting the previous immune response that people have generated. But that can happen. Or, we can have even more infectious versions.

And that is the beauty of life. It has tremendous possibilities and variations. And viruses are in billions and billions; in each individual, they have the luxury of trying out many things. Even if 99% fail, even that 1% will be too much for us to handle. They have extremely big strength in numbers.

This has emerged from the UK because they are monitoring by sequencing. We must also be constantly doing this surveillance and monitor what kind of sequences are emerging because, remember, India has the second largest collection of this virus. So we have greater potential to discover new variants. New variants are constantly appearing, but since they are of no consequence, they remain only in academic circles and databases and do not reach the public. But it can happen that, because of this number [of COVID-19 cases in India], we will have more variants, which sometimes can be a bother for us. That is why we need to contain as much as possible.

You said that you have studied some 5,000 mutations. Are these data being constantly generated? Who else is studying mutations, and how does all of this come together to fashion a public health policy or response?

These things are very well organised. There is an international database (GISAID) initiated in Germany for all such kinds of viruses and it has been commonly adopted; all the sequences will be deposited there. India has deposited several thousands, and the rest of the world is depositing in the same place. So we not only study those genomes isolated from our population, but also have access to all others and so does the rest of the world. All of us pool data in the same place.

We have also simultaneously made apps that are publicly available. We call it GEAR-19--[it is] very user friendly. You can go and play with that and you will find what kinds of viruses are floating around, what age, what region, etc. We do almost daily updates so that almost all information is readily available. We also pool some sequences that are not in the GISAID but in some other databases. So there are multiple internet resources available free of cost, and that is how we keep monitoring what is happening elsewhere.

The key thing is how much we are sequencing and depositing. Today, we are saying that we have not seen this variant in India. That is because we have not opened our eyes enough. If we look carefully we will find, I am sure. I will be really pleasantly surprised if we do not find, in the next three-four days, several numbers of these variants because people have been coming. If 60% of the infections in these regions are from this [variant], whoever had come already [probably carries this strain]...and as this is more infectious, it will be spreading fast.

Is there any correlation between geography or race with mutations, or is it just coincidence that it starts in one place and then spreads?

There has always been a curiosity [as to] why Indians face less severity [of COVID-19], although we get infected. What is the reason for that? Is it our genome, or ethnicity that matters? So far, there is nothing that is well established. In that way, this virus is very democratic--whoever it finds, rich or poor, whichever race, it just welcomes with equal warmth and occupies [the body].

You said that the vaccines developed for COVID-19 should work against this strain. If it does not, or if it looks like it is not having the same impact, what kind of work is required to make sure that it will also combat this mutation and forthcoming mutations?

As far as this mutation is concerned, I understand that Pfizer and Moderna have done quick experiments to see whether the antibodies generated by their vaccines have a neutralisation effect [on the new strain], which means that they are likely to work--although that is in-vitro system [or in the lab].

But even otherwise, this mutation is affecting one part of the surface of the virus. The vaccines that induce antibody response are of multiple kinds and they will touch the virus from multiple sides, even if the same protein is there. That means, even if they are changed a little bit, a few other epitopes--the exposed surface of the protein when the virus enters the body--will be available for the antibodies to catch and neutralise it.

So, in all probability, even the RNA vaccines that are targeting the same spike protein that have mutated should work. On the other hand, vaccines from Oxford AstraZeneca and Bharat Biotech (Covaxin) of India are more likely to be unaffected even more. They attack the virus; they use the whole virus as the vaccine after in-activating and making it harmless. So they are less likely to be affected.

Having said that, in future, there may be some major change in the protein and particularly mRNA vaccines may not be effective. But luckily, although the mRNA vaccine is the first of its kind, this is the technology of the future because we can change the vaccine in any simple lab with a very simple procedure within a matter of weeks. And we can have a new version of the vaccine. Of course, it needs to be tried [to see] whether it is effective and all that. But this makes the vaccine approach much more convenient and I am sure, sooner or later, a large number of companies and countries will produce this more locally.

So we have several new things coming. I mean, it is a dream run for a vaccine--within less than a year you have a vaccine. Although it is [for] an emergency usage--we should not say that we have approved a vaccine--but we have something that gives us some hope. It has emergency use approval and that is simply amazing. We only hope that this will give us protection of a more robust kind, for a longer duration--but that, only time will tell. Because if it is effective after one year, we will be able to tell that only after a year. We cannot fast forward that part.

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