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Dr. Drew Weissman explains why mRNA vaccines can adapt to variants and why we need to get vaccinated

By Binayak Dasgupta, Hindustan Times


The earliest couple of coronavirus vaccines the world had access to were by Pfizer-BioNTech and Moderna. They have high efficacy rates, and produce some of the strongest immune responses among all Covid-19 vaccines.


Common among the two is also their platform – modified mRNA coated in a lipid nano-particle. This technology is the result of research by two scientists, Drew Weissman and Katalin Kariko.


In a video interview with Hindustan Times, Drew Weissman, professor at Perelman School of Medicine at the University of Pennsylvania, spoke about the platform’s development and future possibilities in finding new cures, while urging the world to focus on vaccinating the global population quickly.


Edited Excerpts:


Tell us a little about your journey in developing the platform. The first time RNA was used as a therapeutic was in 1990. I moved to Penn in 1997 and that’s when I met Kati Kariko. My interest at the time was in a subset of immune cells involved in vaccines. Part of the study was in developing new kinds of vaccines. Kati was working on mRNA. We met, we started talking, and started working on mRNA vaccines. What I noticed early on was RNA was highly inflammatory, and that’s bad when you are trying to make a drug, vaccine, or a therapeutic. So we spent a bunch of years studying that inflammatory activity, and finally figured out how to get rid of it, and that was by modifying one of the RNA code. We published that (paper reporting the success) in 2005, and that’s the technology that Moderna and Pfizer-BioNTech use in their vaccines. Kati moved to BioNTech, where she developed the LNP technology (liquid nano particles – the way mRNA is delivered), which is also a crucial part of the Pfizer and Moderna vaccines.


So essentially, the 2005 finding was a turning point for the potential of mRNA vaccines?Definitely. Some people have continued to study unmodified RNA.


They are using the same LNP (delivery mechanism) that Pfizer is using, but if you compare their results to Pfizer’s, Pfizer makes antibodies about five times higher than people recovering from Covid. Curevac, which uses the same immunogen (mRNA wrapped in LNP) but with unmodified RNA, makes antibodies in the lower quartile -- much less than the Pfizer vaccine. The comparison tells you the importance of modified RNA.


How did mRNA platforms role come into play with Covid-19?

Initially, what happened is companies used the tech they knew best. A big problem with science is that when a company develops a vaccine, they don’t compare it with what others do because they do not want to know how much better or worse their product is.


What BioNTech did was a four-arm Phase 1 study and compared different RNA platforms - they looked at unmodified RNA, nucleoside-modified RNA (the method Weissman and Kariko pioneered) and self-replicating RNA. And they found nucleoside-modified worked best for Covid.


The mRNA vaccines are expensive as far as LMIC nations are concerned. How do we look at making it more accessible?

It is expensive because it’s brand new. The companies have just figured out how to make 100 million doses a month. Over time, I believe it is going to get less and less expensive. The other big difficulty is the freezing that it requires. We and other companies are working on how to make it stable in our refrigerators, how to freeze-dry it so that it can be stored at room temperature. All of those advances are going to come over the next few months. Many of those are issues we can address.


My lab and me, personally, have had a big issue with equality of vaccine access. So early last spring, we started working with the government of Thailand to build their own RNA vaccines and their own GMP centres (production facilities). They are going to be able to make the vaccine in Thailand and supply it to seven surrounding LMIC. I am also working with the WHO to do the same thing in Africa so that same access is available.


Is the end of the year a realistic time-frame for some of this?

With the Thai vaccine, the hope is to give it to people by the end of this year. It goes to a bunch of countries, like Vietnam, Pakistan, Malaysia and some others.


What sort of role mRNA can play in keeping up with variants?

The vaccine is literally plug and play. All you need is the sequence of the antigen. For the coronavirus, it’s the spike protein. The minute new variants appear that look concerning, you can take the sequence of the variant and plug it into an RNA vaccine. It will take you literally weeks to make a new vaccine. That’s because the technology is the same no matter what the sequence. [But] if you have to make an adenovirus or an inactivated virus, you have to make the virus, grow it, inactivate it -- all that takes a lot of time.


Can you share some details about the vaccine you are working on with WHO, especially issues relating to intellectual property?

Right now, it is an unknown. The IP is always an issue. People are always working on that to make the IP available. This involves negotiations. Moderna said they would not hold an IP for any Covid-19 vaccine so other companies are free to use it. I think that is a great step forward.


As far as building a facility, a GMP unit (for mRNA vaccines) costs millions of dollars to build. Then you need to get the technology transferred. That’s what we are working on with WHO to get the technology so that we will be able to go in to a GMP facility somewhere in Africa and help them set up to make an mRNA-LNP vaccine. I think that’s the critical difficulty people will have. Once we give them the technology, they can start making the vaccines and that starts takes weeks.


What other doors do you think the modified RNA platform will now open?We have five Phase 1 trials for other vaccines with mRNA before the pandemic hit. We and other companies have clinical trials that are being set up to deliver monoclonal antibodies as mRNA. We have some gene therapy clinical trials that we look forward to. We are setting up to do HIV cure studies in macaques. There’s really a huge amount of technologies and therapeutics that we are developing with modified RNA.


Where do you think we will be this time next year, April 2022?I am a little concerned because in the United States we have fantastic vaccine roll-out, Israel has good coverage and so has UK; Europe has not done well, and then rest of the world has little access. India has access because of Serum Institute but their roll-out is not as fast as wanted and the vaccine availability isn’t great.


There are two things that have to happen for us to get the pandemic under control and stop the variants from appearing. We have to vaccinate the entire world, and countries need to have a high enough percentage of people vaccinated – somewhere between 75-85% in order to reach herd immunity.


When that happens, Covid won’t go away but the variants won’t appear quickly, and the virus won’t spread.


I don’t know how quickly that happens, but until it does, variants will keep appearing. And they are going to keep getting scarier and scarier. The world really needs to get moving on this. It’s just as much about convincing people to get vaccines – in the US, we are reaching a point where there are more vaccines than people willing to take them, and that’s a big problem.


What people who are hesitant do not realise is that if they don’t take it, we are never going to reach herd immunity, and Covid is going to be a problem for years and years to come.


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