Gagandeep Kang backs 12-week interval for second dose of Covishield, says move based on real-world data

These are recommendations of real experts in modelling who predicted mid-May to the end of May as being the time when we would begin to see tapering. And I think what we are seeing is that they are possibly right. We are at the early stages of a flat or declining pattern, which is somewhat complicated by the fact that the testing has also been quite variable. Some of the reports that we are hearing is that there is less testing going on in places that have a lot of diseases where you would expect that as you increase disease in a particular place, you should be increasing testing. And my understanding is that in many places, that's not happening.

You've been tasked by the Karnataka government recently to help with their vaccination strategy protocol going forward. The key issue is vaccine shortage, with multiple states now floating global tenders. The Govt has said there will be over 2 Bn doses available from August through December in India. What do you make of the projection? 

So, I take projections with a grain of salt. Because if you remember last year, we were told last year, that Serum Institute was going to be producing 100 million doses of vaccine a month by December. Then Bharat Biotech was going to be producing in the 10s of millions of doses by December. There was going to be a large stockpile that was available with them. As we found that that has not been the case. And now the 100 million a month has been pushed to the latter half of the season. So, when we project to say that there is going to be 2 billion doses of vaccine in the last five months of this year. I'm a bit skeptical because we haven't seen the previous predictions play out well.

And when I look at that list, I see vaccines for which we have no data. We know that in general nasal vaccines don't work very well, against many respiratory infections. And while it sounds like a brilliant solution, and I really hope it works, I would like to wait until I see the data. Similarly, DNA vaccine, we’ve never had a licensed DNA vaccine for humans. Once again, it is a new technology developed, the vaccine development has taken place entirely in India, and I would be very supportive of this vaccine. But I'd like to see the Phase 3 data for that before thinking that this is a valuable addition to the vaccines that we are likely to have. So, I think the projections are a bit optimistic, I hope very much that I am completely wrong, and the government is completely right. But we'll have to just wait and see.

But Dr. Kang, there were similar doubts raised in January as well when Covaxin got approval that why was this given in a clinical trial mode without efficacy data being published? Just a few months down the line, it has become widely accepted. Covaxin later published efficacy data. So, do you think that this is a risk that perhaps the government is taking based on track record based on their proven history? Because I remember on Covaxin, you said in January that I'm not going to take this till the efficacy data is published. And a few months down the line, you said that Covishield- Covaxin both of them work well. So, I mean, should we be hopeful that something similar could happen here as well?

I think there's a difference between faith and science. We know that when you do Phase 1 and Phase 2 studies, you're looking at safety and immunogenicity. And immunogenicity can be a good prediction of whether vaccines will work or not. But it's not a perfect predictor. And it doesn't tell you how well vaccines are going to work.

And if you want to be able to look at vaccines, and really say that they work, either you need an immunogenicity marker, which is a correlate of protection, or you need clinical efficacy data. At the point, at which Covaxin was approved for restricted use in clinical trial mode, there was no correlate of protection, and there was no clinical efficacy data.

Also Read: Dr Gagandeep Kang: I take govt projections on vaccine with a grain of salt, nasal and DNA vaccines have no data yet

So, what I said at that time, and I stand by it, is that I don't think we should be licensing vaccines for which we have no indication of whether they work or not. Once the clinical efficacy data became available, even as an interim analysis, then I'm willing to accept a vaccine.

The government placed a bet. And it was a correct bet to place in that view. But I think if you look at if you want credibility in your regulatory process, then if you lay out a pathway for a vaccine, then stick to that pathway. Why are there regulators? The regulators are there to ensure that there is data that informs the quality of a vaccine, the safety of the vaccine, and the efficacy of the vaccine.

Dr. Kang on paper, the vaccination procurement schedule looks promising, but as you said,  we haven't seen that proof of these companies being able to ramp up capacity. So, what is the alternative here? Dr Devi Shetty for example said India should just buy as one, buy in bulk, whatever vaccines have been approved globally.

Central procurement for anything that is in the national immunisation program is something that the government has done forever. It's always been that anything being bought, any vaccines being bought for the national program, are bought by the Center and distributed to the states and then the states run their immunization programs.

Last year, in August, the government had said, we will go for central procurement, and told the states there is no reason for you to go for your own procurement measures. This changed overnight in April. Now states which I could have done this months ago, are at the back of the queue where any the manufacturer is concerned because so far, they want domestic manufacturers, they haven't talked to international manufacturers, they are literally going to be told overnight that in two weeks, three weeks, you're now responsible for two-thirds of your population. How are they expected to deal with this?

I completely agree with Dr Devi Shetty that there needs to be central procurement, but there was never a need to set up for states to procure again, you're creating a market where it's free for all. Now if you have a manufacturer that's located in Maharashtra or in Telangana, are they going to be providing vaccines to let's say, Himachal Pradesh or Uttarakhand before they provide to Maharashtra and Telangana.

It is unnecessary to have this level of complication. It's an opportunity cost for everybody involved in central procurement would have been the simpler solution. After all, ultimately, if vaccines are free for everybody, which has been the way, it has been in the vaccination program, it is good for all of us.

The immediate concern is also the third wave and how it's going to particularly impact children. Will enough young parents be vaccinated by then? How can we really prepare for the third wave? Or do you believe there will be enough for protection by then because a significant percentage of the population could have been impacted through the second?

I don't understand why we think in terms of the second wave, will there be a third wave?  I think the way we are beginning to understand this virus is that the biggest thing that I don't understand is why did the first wave die down? I mean, the manner in which it did.

That leads me to think that there must be, obviously in terms of spread, there are significant behavioral drivers because we have an understanding that, there is behavior led to the size of the second wave. We also know that variants play a role.

But I think there are also environmental drivers, and as more and more people are exposed to the virus or are vaccinated, I think we will see the environmental drivers and the viral determinants, the variation in the virus that will determine what future waves look like. And if we don't get a reasonable handle on control through vaccination, or sadly, through too much of the population being infected, I think we're going to wind up with this virus potentially being seasonal.

And thus seeing one or more waves a year. With Influenza, for example, India has two waves every year. And we don't talk about Influenza and the waves. Will SARS-CoV-2 settle down and be rather like Influenza? It's very possible. But we need to understand a lot more. We are understanding more about temperature, humidity, and how they drive the survival of this virus in the environment.

And I think we will begin to understand more about the drivers of seasonality as we complete two years with this virus. We'll be able to predict better what future waves will look like. I don't think that we will avoid a third or a fourth or fifth wave, but the sizes will depend very much on infection, vaccination, and behavior.

The other change that the government recently was increasing the interval between two doses of Covishield. We increased it from 6-8 weeks 12 -16 weeks, and the UK government, in fact, brought it down because of the Indian variant. So again, do you think this is rooted in science, is this more of a supply issue, is the government doing this only because we do not have enough vaccines in the market now?

So, based on the science I've been recommending, I think since February, that we should be increasing the dose for Covishield to 12 weeks. Now that is based on real-world data that has come from the UK, looking at the B117 variant, which was the predominant way circulating in that country.

Now, I know that everyone's really worried about B1617, including in the UK where they're doing a lot more sequencing than we are doing in India today. But in India, it's not clear to me where B1617 is the predominant strain across the country. And when it became predominant.

We still have a lot of B117, in which case, the recommendation of B117 in 12 weeks still holds, and for B1617, if we argue that our laboratory data is showing us that you will get as much protection against B1617, as you do with B117, then I don't see the need to switch to a shorter duration. Also, in the UK, important to remember, that the recommendation is 50 and above, right. So, I think we need to look at the data. We need to gather real-world evidence in India before we chop and change.

I'm not uncomfortable with a 12-week interval with the Covishield vaccine, something I've been saying since February, still saying in May, but I'd really like for us to have real-time data that drives our decisions about what are the variants that are circulating in various parts of the country? How well are the vaccines working against each of the vaccines, how well are they working?

Right now, we've got 180 million doses of vaccine have been given out since January? We should have data on how well the vaccines are working. And we should have data on how well the vaccines are working against different variants if we are to make science-based decisions.