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Different Covid Vaccine Doses Are Fine, Might Work Better: Virologist

The B.1.617 Covid-19 variant, originally identified in India, appears more infectious than earlier variants but even one dose of a Covid-19 vaccine will give some protection against it, says Polly Roy, professor of virology. India should prioritise vaccinating everyone with at least one dose, and using different vaccines for the first and second doses is a good idea.

Different Covid Vaccine Doses Are Fine, Might Work Better: Virologist
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Mumbai: India does not have enough Covid-19 vaccine doses to vaccinate the entire country, or even the groups of people who must be vaccinated in the government's recommended timeframe. There are not enough vaccines to distribute within cities, across the country and across age groups. This compounds the problem of Covid-19 spreading faster, or coming back in new waves.

Another set of problems is that the Indian variant--the B.1.617 mutation of the SARS-CoV-2 virus--seems to be spreading very fast not just in India but also in other parts of the world. What do we know about this mutation? What can we understand better about how it will spread? Given where India stands on vaccine supplies and the likely pace at which these will be rolled out, what do we need to do next? About 191 million Covid-19 vaccine doses have been administered in India as of May 22, but of this, only 41.5 million (3%) of a 1.3 billion-plus population are fully vaccinated with two doses, which is not enough.

To understand more about the Indian variant as well as whether vaccines will respond to it, we spoke with Polly Roy, professor of virology in the Department of Pathogen Molecular Biology in the Infectious and Tropical Diseases faculty at the London School of Hygiene & Tropical Medicine. Roy received her PhD in molecular virology from Columbia University's medical school in New York, US, and post-doctorate continued to study RNA virology at the Waksman Institute of Microbiology at Rutgers University, New Jersey, US. For the last three decades, the predominant subject of Roy's work has been the bluetongue virus or BTV, a complex layered virus of the reoviridae family. Roy's work has been recognised around the world and she has received many awards, including Officer of the Order of the British Empire for service in virus research; Fellowship of the Academy of Medical Sciences, UK; and the Indian Science Congress General President's Gold medal, awarded by the Prime Minister of India. Roy was also a finalist of the Biotechnology and Biological Sciences Research Council's 'Innovator of the Year' award.


Edited excerpts:

The B.1.617 variant appears to be more infectious than mutations we have seen earlier. What do we know about this mutation now? Could its spread worsen?

This mutation appears to have a drastic change in the receptor-binding site of the virus. This is also the same site that some vaccines target, which is a problem. But, the vaccines are very robust in making neutralising antibodies, and they target the entire spike protein, so they will still give some protection [against the B.1.617 variant]. Even if you have just the first vaccine dose, you still get some protection against the COVID-19 disease, if not completely against infection. The disease will be cut down a lot, so it's not as much a disaster situation as we think.

Tell us more about this B.1.617 mutation. Is this the most dangerous possible mutation, and could it get worse? What is the usual journey for mutations like this, specifically in the context of SARS?

Most mutations everywhere are seeing a change in the receptor-binding site of the spike [protein]. But some of the changes are not as bad as the Indian one, which is a drastic change. And that may allow them [virus particles] better entry than the original Covid-19 virus. The vaccine made was also on the original virus base. So [the vaccines] may not recognise [the Indian variant] completely.

The virus changes a little bit, silently, and then it will change drastically. This is the nature of the virus. Viruses make errors continuously, because they are making a copy of the genome. And often, those errors are not important, but [when made] on certain sites, they are important. This particular position [in B.1.617] appears to be important and also very exposed to change too much. Transmission is occurring [very quickly], that is why [the virus] changed. It would not have been that way if we controlled it beforehand.

Could we have been better prepared for this virus mutation?

Absolutely. If you had two things, isolation and distance between people [and no] gatherings, because that allows transmission. Another problem with this SARS-CoV-2 [the virus that causes Covid-19] is it's asymptomatic in many, many people. Not everybody can show the disease. When the virus first infects a certain person, they don't even feel it. Sometimes you don't feel anything while another person will feel it more. But the problem is after three days, when you realise that you don't feel good, this virus has already almost finished its job. So, if you are not separated from other groups, you have already given it to a whole lot of people without knowing it.

In India, the first lockdown was very good, [the virus] started disappearing. But it didn't. The virus is still there. India has a very large young population compared to other countries and they are asymptomatic most of the time, because the virus is moving slowly [in them] and in small amounts, not high doses. Older bodies cannot really accept the virus because they have less innate immunity than younger people. But when the viral load is high, younger or older, all are getting infected. That's what happened in India. With [wide] transmission, the virus can change quickly. They make errors [when replicating] and some errors are very good for them, not good for the host. That's what has happened. But that still doesn't mean the virus has taken over completely. There are many other epitopes [that antibodies can target], and there is a T-cell response as well. That doesn't change.

Currently, at least in some cities, we are seeing the numbers of new infections ease off in this second wave, though in many parts of rural India cases are still high and there is also a problem of undercounting cases. But assuming there is an easing off, what could happen next?

Easing off in one place and not easing off in another place is always challenging because people are still going to travel by train, flight or car and that is frightening for me. So, we have to be very cautious until 70% of people are protected, so that the susceptible population is smaller. But, vaccines are the best. If you can give vaccines to that many people, then we are [in a] very good [situation]. Otherwise, we have to keep avoiding aerosols, because [Covid-19] is spread [through the] air by aerosols. So that should be our mantra all the time--aerosol, aerosol, aerosol. Remember air transmission. Don't go into dense populations. Keep yourself safe by not going near somebody. People think handshaking is bad, but that's not necessarily so. It is the distance that's very important. You don't know who is infected and who isn't. You don't know because they don't know.

We have two vaccines currently being administered in India--Covishield and Covaxin. The Sputnik-V vaccine from Russia is going to start production but it is going to take time. Maybe India should have been vaccinating about 10 million people every day, but some days the numbers are closer to one million. There's a lot of vaccine hesitancy as well. Another problem is that some people have got their first dose of Covishield but can't get the second dose quickly, and the government is trying to manage this by increasing the gap between the two doses. How do you look at this in terms of vaccine efficacy?

All the vaccines that India has are highly efficacious, definitely. Less is known about Covaxin, because they have not done a lot of work on that yet, not a lot of people have got that vaccine. Covishield has been given to many people and it is very good. One dose is enough to stop the disease, if not the infection in most people. Sometimes, people say they have been reinfected after vaccination but they may have gotten infected just after a week, or two days before vaccination. Nobody knows when you're getting an infection. It takes two to three days before you feel bad. So [there] is a vaccine effect. People are very happy to talk about side-effects of vaccines, which is not a good thing to do because you get side-effects with paracetamol as well. Ibuprofen gives side-effects to some people. So, even if you get some side-effects, everybody should think that 'I must take the vaccine'.

Earlier, the government said the ideal gap between Covishield doses is 30-40 days. Then it became about 60 days. Now, it is suggested there should be 90 days before the second dose. In India now, because of shortages, it is not clear whether people can get that second dose of Covishield in time. What happens then?

Even if you don't get the second dose, you're not going to get so badly sick that you will have to go to the hospital. Even the first dose [of Covishield] should give you enough protection.

Till when will you not get sick [after the first dose of the Covishield vaccine]?

[Once vaccinated] if you get infected, you will get a little bit of fever, a little uneasiness, but you are not going to be on your deathbed. So, I would think that it's best that everybody gets at least one dose if there are fewer vaccines available. Evidence from other countries suggests that the antibodies generated after the first dose of AstraZeneca's vaccine (Covishield in India) protect you for up to six months.

Six months is how long the first dose will protect you, without getting the second dose?

Definitely, there are some antibodies circulating [in the body]. It is a good idea to have a second dose if possible but if not, it is still okay. It is not so bad not to have the second dose. If you don't have vaccines, what do you do? You have to have everybody take the vaccines. So, one dose is good enough.

Assuming you've taken both doses, how long does it keep you protected or safe?

Nobody knows that, because what we test in neutralising antibodies in animal samples doesn't really equate to actual cases. Antibodies should last for a while because the second dose gives high levels. It should last for at least a year, if not more. It depends also [from] person to person, because for those who already have [health] problems--people with diabetes, or high blood pressure, cardiac or lung problems--it's questionable how long they can sustain the antibodies. But for generally healthy people, it is not so much of a problem. The vaccine is very similar [to those] for any viral disease.

A lot of people, particularly frontline workers, have taken both the Covishield doses quickly, within 30 days, during the first phase of vaccination in India. Are they better off, or not, because the subsequent advice seems to be that you should spread doses further apart for better efficacy?

All vaccines are good [when administered] 21 or 30 days apart, generally, between primer and booster shots. Covishield has a vector [the adenovirus], and the body develops some immunity to the vector as well. So, the neutralising antibodies could stop the vector at the second dose. So, there may be a better response if [the doses are] further apart. This is one reason they are [extending the gap]. The most important reason they are doing that, I think, is because you don't have enough vaccines available for everybody. And that is why it must be economised that way. Nothing wrong with giving doses 30 days apart.

Another question increasingly cropping up in India is, can different vaccines be mixed and matched? Is that going to be dangerous for me, particularly if I'm not getting the vaccine that I want?

No, it is not dangerous at all. It is better. I already said months ago that vaccines should be mixed and matched. The data just came out from [a study of 673 people who took a dose of] AstraZeneca followed by [a dose of] Pfizer [vaccines] in Spain. And 600 people have much better [neutralising antibodies] and much higher than if you take the same type of vaccine twice. Mixing-and-matching could be very good, as has been done with the Ebola virus successfully before. So, I think that is a very good idea.

So instead of thinking of it as a plan B, you should actually actively try and get two doses of different vaccines?

Yes, I think it's going to go that way, I am sure about that. Most virologists know about this. I make a lot of veterinary virus vaccines, and I know that. And I think it would be very good also for India to mix-match the two vaccines they have currently.

So, are you saying you can have one Covishield and one Covaxin dose?

Yes, of course. Biologically, there is no problem with that.

India now has the Sputnik V vaccine, which is going to be rolled out. Different states are also trying to import other vaccines. So as more vaccines come, should people just take whatever vaccine they can get their hands on and it's fine?

Yes. In my knowledge and experience, I feel Sputnik V is one of the best vaccines because of the way it was made. They designed it very nicely. From the beginning, they are getting 91-92% protection in their clinical trial. They showed that.

I think we should try to mix and match vaccines in every country to make sure that we get the best protection, best neutralising antibodies.

When you look at the data from clinical trials for all the Covid-19 vaccines that we have talked about, are you satisfied with the quality of data and the insights they give?

Yes, these days, regulatory organisations in every country are very strict about that. You have to go through the phase 3 trials. Phase 1 and 2 are sometimes clubbed, but phase 3 trials are very important. Thousands of people have to be vaccinated and it is very important to mix age groups and people from different countries, if possible, to see any genetic differences. In my view, all people will have similar effects more or less, but this may differ among age groups. AstraZeneca, Pfizer and Moderna have all done very well in that. Sputnik V did [Phase 3 trials] at the end. In the beginning, they did not but they have also done very good Phase 3 trials. Covaxin, I don't know yet whether they have done well or not in the phase 3 trials, how many they have done, I did not see the report yet.

One concern emerging now in India and in other parts of the world is about children. Should children get vaccinated against Covid-19? If they do, is there something that we should be concerned about?

Children are not so susceptible to this disease anyway--maybe to infection, but not to the disease so much. So adults have to be considered first and then if there are opportunities, children should take the vaccines. Nothing bad will happen to them. They are not very good spreaders of Covid-19 either. Young adults will spread the virus but not children, because the virus does not affect their body very much. But if the children have taken vaccines as well as adults, then this virus will disappear from everywhere. Globally, that's what we want. We cannot just say we protected this country, that country or that region. I know Delhi is in a very good situation right now but you still have a lot of transmission on the outskirts of Delhi. So, that doesn't help you, because somebody will bring it back again if you are not vaccinated. But if you are already infected of course, you are not going to catch the virus that easily again.

There's nothing medically dangerous with a child, i.e. around 10 years old or younger, getting vaccinated?

Yes, 10 years old or younger. But we don't have to worry about them so much yet. The vaccine is still not so abundantly available that everybody can take it. Don't push for children getting vaccinated so fast. But yes, eventually they should take it.

Schools have now been shut for more than a year and parents are anxious whether children can or should go back to school. If so, should they be vaccinated? This is a global question.

It's a question in the UK too, but here, everybody has gone back to school and they will eventually get vaccinated also. As I said, children are not very good spreaders of Covid-19. They can pick up the virus and may bring it home to adults, so adults have to be vaccinated first. Teachers have to be vaccinated first before children can go back to school. America has already started vaccinating children aged 13 years and above. They will probably wait for a while until we have a lot of vaccines to vaccinate the younger ones. It doesn't do any harm. When people talk of side-effects, I think a lot of these are just stories, not necessarily directly relevant to the vaccine.

To come back to the current B.1.617 mutation, and potentially future mutations, would Covid-19 vaccines also need to be re-engineered, and can they be re-engineered quickly enough? Would it also mean that every year we would need a booster shot re-engineered to accommodate newer variants? How does that work?

[Re-engineering] both adenovirus-based [like Covishield] and RNA-based vaccines like Pfizer and Moderna is very easy. Particularly with Pfizer and Moderna. It's very easy to make vaccines for new variants. Genetic engineers make changes all the time. That's not a problem. The major problem is manufacturing. So I suggest that almost every country including India should have many manufacturing places, and not only one place where everything is done. If something goes wrong there, then that's it. That is not good.

After a few years, maybe you will never see SARS [Cov-2] again. Maybe it will disappear completely, so we have to just be proactive. I still think the best thing is that we be a little bit careful about who we are mingling and socialising with. If you know somebody, then you go meet them, or people in your bubble. But if you don't know somebody, how do you know the person doesn't carry the virus? We will have to be a little bit cautious for a year at least, not go to big gatherings.

What are the key lessons that everyone--policy-makers or citizens trying to go about our daily lives--should be aware and focusing on?

Transparency. Everybody has to be honest and transparent. There is no point in hiding something. If you have a problem, share it with the world. That is the only way one can help each other. It's a global problem. Hiding and giving wrong data is not a good idea at all. Everybody has to be transparent. We have to learn this lesson properly and really share the data. In India, you still don't have enough data on sick persons to know what's happening. Not just from one area, for every area you have to see how this particular mutant spread. And India can do it. India is very well-known for good science. Give priority to this and to making vaccines quickly, don't depend on other countries' vaccines.

Also, let the immunologist and virologist be included in decision-making, not only politicians and epidemiologists. Virologists and immunologists know how the virus and immune system work.

Your last bit of advice for readers?

Be very vigilant, don't just jump into everything you see, like these processions and religious gatherings. I am very against all these big gatherings, I find it ridiculous. In today's situation, one should not think about going anywhere just like that anymore. When you lose your loved one, how difficult it becomes to accept that maybe you brought the virus into the home yourself. So it's better to be cautious all the time for a little while. I think India might have to be more cautious for six more months, and then we'll see. It looks like we don't have to be cautious anymore in the UK, they say, but I'm still cautious. I'm not rushing to a cinema or restaurants immediately. You just don't have to do certain things. You have to change your lifestyle a little bit. You have to go with the flow, do whatever is necessary.


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