Vaccines like Biological-E’s Corbevax and Bharat Biotech’s Covaxin that are made by traditional methods are “just as effective” as the latest mRNA technology based vaccines, says U.S. scientist and vaccine developer Dr. Peter Hotez. He announced last week that his research teams would transfer production technology to companies in India, Bangladesh, Indonesia and Botswana free of patents.

According to Dr. Hotez, who is the Dean of Houston-based Baylor College of Medicine’s Tropical Medicines School and Chair at Texas Children’s Hospital, the traditional method “protein subunit vaccines” and “live inactivated vaccines” are cheaper and simpler to produce at the scale required for low and middle income countries.

“We never really saw the advantage of mRNA, at least for a global health vaccine… because it’s a brand new technology and it’s going to take years to figure out how you scale it up to make 9 billion doses for Africa, Southeast Asia and Latin America,” Dr. Hotez told The Hindu in an interview, where he called the new vaccines “shiny new toys”.

Science policy makers, particularly in the U.S., were “too focused” on speed and innovation and not on ensuring universal vaccination, he noted. In particular he said the method developed by him and Dr. Maria Elena Bottazzi through the same “yeast fermentation expression technology” used to make the Recombinant Hepatitis-B vaccine first approved in the 1980s, was also safe for children, and less likely to cause vaccine hesitancy amongst parents, as it has been used for decades.

‘Balance the portfolio’

Given that even after three or four doses mRNA vaccines were not effective in stopping COVID-19 variants like Omicron, it was necessary to “balance the portfolio” by focusing on quantity of vaccines rather than the newest technology, Dr. Hotez observed.

Traditional vaccines such as a virion (entire virus particle) and subunit ones (pathogen fragment) contain inactivated parts of the virus that enter the body as antigens and trigger an immune response. Newer technologies such as the mRNA or DNA vaccines contain modified genes that use the body’s cells to make the immune-triggering antigen. The latter approach is also believed to be quicker and more customisable to making vaccines for several pathogens in the future. However, none of the commercially available COVID-19 vaccines are yet customised to the Delta or Omicron variants.

“Delta arose out of an unvaccinated population in India in 2021. Then Omicron arose out of an unvaccinated population in southern Africa later in the year, and as long as we refuse to vaccinate the world’s low and middle income countries, Mother Nature will continue to deliver horrible new variants of concern,” Dr. Hotez stated. At present the world “just needs vaccines that work”.

Last month, the Drugs Controller General of India (DCGI) cleared Corbevax and the Serum Institute of India-made Covovax for Emergency Use Authorisation (EUA), and approved Covaxin for children aged 12-18. The agency has thus far cleared eight vaccines for EUA, but only three are available- Covishield, Covaxin and Sputnik, due to legal issues over liability, as U.S. companies Pfizer, Moderna and Johnson and Johnson want a sovereign indemnity waiver, which the government has refused to give.

Legal issues

When asked, Dr. Hotez was critical of multinational pharma companies that are delaying supplies due to legal issues, as well as of countries that have not yet okayed a joint proposal by India and South Africa at the World Trade Organisation to waive all patents over COVID-19 vaccines and medicine technology for a few years until the pandemic subsides.

“The idea that millions of people are dying all over the world from COVID-19 while we bicker over indemnity waivers and legalities is unacceptable. When your house is on fire, you don’t start looking at what what the insurance is going to do and who’s indemnified- the house is on fire and we have to save lives,” he pointed out, justifying the decision by BCM-TCH to transfer protein cell banks and coding technology to countries in the developing world without patents. However, he cautioned that simply lifting patents would not solve the problem of capacity, particularly in the African continent, and more vaccine manufacturers were needed.

Dr. Hotez praised the Government of India for lifting the export bans and resuming vaccine supplies to other countries despite the setback and disruption caused by the Delta variant in 2021 that led to massive oxygen shortages and hundreds of thousands of deaths across the country.

Full text of the interview

Why did you decide to announce a free of cost transfer of technology for the traditionally made “Corbevax” vaccine?

Well, just to clarify..the producer of the vaccine and the owner of the vaccine is Biological E in India. Corbevax is their vaccine, and they’re the ones who work out all of the requirements with DCGI. They’re producing 150 million doses and will be producing 1.2 billion doses over the next year. And what we done here at BCM and TCH, we develop the prototype vaccine, the Production cell bank, because it’s made through microbial fermentation in yeast and, and we’ve done this with no patents. We provide the production cell bank to organisations that we feel have the capability to actually turn it into a vaccine. And then we help with the with the code development at our own expense. So now we’ve transferred this technology to Biological E in India, to companies in Indonesia, Bangladesh and Botswana…no patents, no strings attached. 

Was there a particular reason why you chose to develop this through what some would call the method of “old fashioned” vaccines, and not the mRNA route?

Well, we we never really saw the advantage of mRNA, at least for a global health vaccine… because it’s a brand new technology and it’s going to take years to figure out how you scale it up to make 9 billion doses for Africa, Southeast Asia and Latin America. We have shown that our technology, in terms of virus-neutralising antibody immune responses are as effective. The advantage is it uses the same yeast fermentation expression technology used to make the Recombinant Hepatitis-B vaccine. And that point is very important because that vaccine has been around for 40 years, it’s made locally in Indonesia, India, Bangladesh, all over the world. 

I think that was the problem with with the science policymakers and operations like Operation warp speed in the US. Everything was so focused on speed and innovation, that nobody gave a thought to, hey, what are we doing for the world’s low and middle income countries? Now, this is India’s gift to the world, where they are making vaccines for the world, while the rest of the world turns its back on on the global south.

India had a major disruption in its vaccine exports, due to the Delta variant in 2021. And at that time, you had said that the world should not just depend on India for its vaccines. Do you think India can reclaim its position as a global vaccine supplier?

I think it will. And I would even argue maybe it already is taking big steps that way, because it has lifted a lot of those export bans and Bio-E has a commitment to providing vaccine to the COVAX sharing facility for the world. I think if you actually talk to the individual vaccine producers, that commitment in supplying vaccines for the world has never, never wavered. 

In that sense, has global Pharma and many countries failed, by delaying the WTO proposal to waive patents, as proposed by India and South Africa? 

Well, that’s why we bucked the trend and said, we’re going to make our vaccine, and give it to the world. And while the rest of them want to bicker about patents, we’re not going to go down and that direction. But I do feel that even if we were to liberalise all the patent laws, which I think we should, it still wont be enough, unless we try to build more capacity. Because right now, vaccines for all practical purposes are not made on the African continent.

Another legal question is that of indemnity waiver, which US companies want and India has refused…

All I can say is I got my MD and PhD in order to make life saving interventions and the idea that millions of people are dying all over the world from COVID, while we’re bickering about indemnity waivers and legalities is unacceptable. When your house is on fire, you don’t start looking at looking at what what the insurance is going to do and who’s indemnified- the house is on fire and we have to save lives. 

Would you say traditional vaccines like Corbevax and the Indian Covaxin are as effective as other vaccines?

Well, in some ways, perhaps better. I mean, we’re already starting to see their performance while some of the mRNA vaccines may be starting to falter. For example, once individuals get the third dose of the mRNA vaccines, that should provide long lasting, durable protection based on what we know for other vaccines, but it’s not holding up very well against Omicron, and after a few months they say the mRNA vaccines may drop effectiveness by half. When you go with a brand new technology, there’s a learning curve. You have to really balance the portfolio with the old school of vaccines, which may be just as good or better because at least we know their performance features and know something about their durability. So I would suggest balancing what will ensure that everybody gets vaccinated than by going exclusively with what I sometimes call the shiny new toys.

How effective are the traditional vaccines against a variant like Omicron, and do you need to modify the vaccine to target different spike proteins?

Well, we hope not, we do not have the data yet. For Omicron we’re waiting for the Omicron pseudo virus and the actual virus itself and once we get that we’ll know pretty quickly whether the virus-neutralising antibodies to our recombinant protein vaccines will cross-neutralise Omicron. But I will say that we are excited as Corbevax seems to be holding up particularly well against the variants, against delta and beta. So so the hope is that it’ll hold up against Omicron. And but we’ll know more in the coming weeks.

Most Indians have been vaccinated by either Covishield (AstraZeneca) or Covaxin, is there any data about using Corbevax as a booster shot?

I know that Bio E is working with, it’s been reported in the press that they are working with the Indian regulators to look at the vaccine as a booster. And also as a pediatric vaccine, because even though it was released for 18, and up, we think there could be a lot of attractive features for pediatric use, because again, it’s similar technology to the Hepatitis-B vaccine. That’s been going into kid’s arms for four decades. And so we think even parents who are somewhat reluctant about giving mRNA vaccines to their kids might be more accepting of recombinant protein vaccine. We think this will also be useful at countering vaccine hesitancy.

What is more important to vaccinate the world right now — more choices of vaccines or just more vaccine doses?

Right now we need just vaccines that work. I mean, Mother Nature has told us what she has in store for us, right? Delta arose out of an unvaccinated population in India in 2021. Then Omicron arose out of an unvaccinated population in southern Africa later in the year, and as long as we refuse to vaccinate the world’s low and middle income countries, Mother Nature will continue to deliver horrible new variants of concern. So I make the point that it’s both the obvious humanitarian interests of people to to vaccinate the world, but it’s also in their own enlightened self interest to do this as well.