‘Record speed of Covid-19 vaccine development was not at the cost of safety’: Dr. Ruklanthi de Alwis
Sri Lankan viral immunologist working on new vaccine says Covid-19 has accelerated vaccine development processes
By Hiranyada Dewasiri
The development and improvement of Covid-19 vaccines has been trying to keep abreast of the rapid spread and evolution of the Covid-19 virus. As a number of vaccines are being developed around the world from the US to China and England to Russia, The Morning spoke to Sri Lankan viral immunologist based in Singapore Dr. Ruklanthi de Alwis. Currently she is a Senior Research Fellow at the Programme in Emerging Infectious Diseases (EID) and the Viral Research and Experimental Medical Centre (ViREMiCs) at Duke-NUS Medical School where she is collaborating with American biotechnology company Arcturus Therapeutics to develop a vaccine called LUNAR-COV19, which is now at a Phase three trial stage.
We spoke to Dr. de Alwis on the vaccine that she is helping to develop, ethical issues surrounding vaccine trials, intellectual property rights of vaccine manufacturers and pharmaceutical regulations.
Below are excerpts from the interview:
What is the current status of the vaccine that you are developing?
My work is on antibody responses to viral diseases and a lot of my past research work has centered around studying dengue. We focus on what happens after we naturally get infected with these viruses. I also work on vaccine responses. We study the natural immunity responses and translate that into a vaccine that protects us. When Covid-19 started in January last year, we had to drop all our projects because Singapore went into a lockdown. Then we very quickly started working on developing a RNA vaccine for Covid-19. For most of last year, we did the preclinical testing for LUNAR-COV19. The vaccine was first tested on animal models and whether the vaccine can protect animals from SARS-CoV-2 infection. Then we took it to humans. In terms of now, Singapore has all the elements to develop a vaccine. But what is interesting is that it does not have enough cases to test the vaccine for efficacy. Once you come to Phase Three clinical trials, and this is where you truly ask the question of whether the vaccine can protect against disease, you cannot do that in Singapore. For this you take large numbers of people, usually several thousands, you vaccinate half of them and you give the other half a placebo. We follow them up till they get infected from the community. For this you need infections in the community. Until last month, Singapore had no community transmission. So, it was not possible to test a vaccine and even now it is not high enough. So, we came all the way to Phase Two and now Phase Three is happening in several countries including the United States.
Are you involved in studying any other vaccines?
We are academics and although we collaborate to develop vaccines, we also study the antibody responses to other vaccines. Currently we are studying responses to the Pfizer-BioNTech vaccine which is approved in Singapore. Another reason we want to do that is because our vaccine is also an RNA vaccine candidate but it is a newer form. In RNA vaccines, what we give a person is the nucleic acid. It’s covered in a spherical envelope called lipid nanoparticles to protect it. It is not like giving a protein or a virus. Once the nucleic acid is given to the body, the person uses that information to make the protein. This amounts to the immune response. So, our RNA vaccine is a new technology. Before Covid-19 there wasn’t a single RNA vaccine approved. But since Covid-19 there are two approved – Pfizer BioNTech and Moderna. It seems that RNA vaccines have done very well in terms of efficacy. They are the ones showing more than 95% efficacy. In terms of a pandemic response, RNA vaccines are much easier to manufacture. You can make a lot of doses very quickly. Now, people are worried whether the vaccine would protect them against new variants. It is also very easy to change RNA vaccines when the virus mutates.
What changes have you experienced in vaccine development for Covid-19 in comparison to your pre-Covid-19 experiences?
Covid-19 has really changed the way that we license vaccines and therapeutics. Usually what we do in vaccine development is that we start working with animal models like mice, rabbits and then human primates. It is unethical to try it on humans right away. In the normal vaccine development stage, you would first go through the pre-clinical stage, Phase One clinical trials where you go into humans, and then only you would submit your regulatory packages to the drug administration that approves your vaccine. It is usually done sequentially. But we don’t have that time with Covid-19. So, at the time we started testing the first vaccination in mice, we started engaging the regulators. They were with us in the development process. This sped things up in terms of development. If the regulators thought that the data was not sufficient, they would tell us. This was something new and improved that came out of Covid-19 vaccine development and we hope that this would translate into other vaccines as well so that we have vaccines in the market faster.
What are the ethical challenges faced in developing a vaccine for Covid-19?
When it comes to testing, treatments are usually given to a sick person. The ethical justification in giving a treatment to a sick person is quite apparent, especially if there is nothing else the doctors can do. When it comes to clinical trials for vaccines, the vaccine is always given to a healthy person. The ethical issue is that we need to make sure that it is safe. But since it was a pandemic situation that was quite bad, there were definitely ethical reasons to push those trials. This does not mean that the safety was jeopardised. That’s why regulators were engaged from the beginning. That is something that we need to keep in mind even for the adenovirus vaccines that are showing some rare side effects with blood clotting. Thrombosis (the process of blood clotting) is much higher in a SARS-2 infection. There is always a risk in vaccines. But in this case, you are far more protected from Covid-19 which really is the bigger issue here than the rare side effects. Especially in the current instance where we have variants. It’s an RNA virus and they mutate faster than others. We should be aware that vaccines need to be given populations fast so that we are protected against the variants. The more time we take, the more the virus will evolve. Possibly even away from the vaccine. There is talk that the efficacy drops and even if it drops, at the end of the day, what matters is how the vaccine protects against the disease and keeps people out of hospital.
Could you explain to us the concept of a universal vaccine?
The current strategy is that we have a vaccine, we immunise people, and over time the vaccine slowly changes. Every time a variant escapes a vaccine, we are rushing to change the vaccine. The other way we go about is that we don’t chase the virus, but we make a vaccine that is going to provide protection against multiple variants. A universal vaccine does not wait for the variants to come, They protect you against multiple variants at the get go. We need a lot more research on this to understand the components that will lead to what is known as cross protection. This is something that came down from influenza. The influenza world has a lot of experience on this. Currently we have no licenses for universal vaccines, but the influenza field is ahead of many other virus fields. There are a lot we have learnt from influenza and the current pandemic which we have tried to integrate into our vaccine design. Many groups across the world are thinking of universal vaccines and at the rate at which Covid-19 research is progressing, I wouldn’t be surprised if some cross-protected vaccine candidates go into human trials by the end of the year.
There are ongoing studies about mixing and matching vaccines and as of recent, Sri Lanka has also been showing interest in this possibility. Has this shown any success?
There are tons of different kinds of vaccines out there and people are studying what happens when you sequentially give two different kinds. Biologically, it may produce different immune responses, who knows? Not much is known about what is going to happen. Lots of these studies are being done because many people won’t have access to two doses of the same vaccine. We actually don’t have data on this. I think Sri Lanka is a good place to start. In Singapore, we only have Pfizer BioNTech and Moderna so we can’t test that because they are both RNA vaccines. It would be interesting to see what would be the response if you get the first dose from Oxford Astra-Zeneca which is Adenovirus vector vaccine and Sinopharm is an inactivated virus vaccine. Those are very important questions we need answered.
Vaccine companies and developers have claimed Intellectual Property (IP) rights to their vaccines which in a way has imposed certain limitations on vaccine accessibility. How important are IPs at a crisis time such as this?
If a company spends a lot of resources in developing a vaccine, they should protect their IP. However, there is a moral and ethical issue right now with coronavirus. Is it correct to talk about IP when a lot of people are dying? These companies are also developing these vaccines with the majority of the funding that came from governments, donations, Global Alliance for Vaccines and Immunisation (GAVI), Covax. There are other entities that have paid for these vaccines and because of this they have a moral obligation to provide these vaccines for people who need it. That is the only place that it is worth trumping the IP. IPs are important for the development of research but this is a different scenario. In terms of manufacturing, a lot of companies are doing this in two ways. Some Chinese companies are already working with governments to set up factories in other countries. One of the nicest examples is the Oxford vaccine because they developed what’s known as a non-profit vaccine because they are academic. They did license it out partially to Astra-Zeneca. We need to keep in mind that Big Pharma is also important as it tends to have the resources, network, the people and the know-how to quickly push forward clinical trials. They also gave licensure to Serum Institute of India. SII can provide large quantities of the vaccine for a cheaper price. These partnerships are happening, but we still hear about countries hoarding vaccines. I think they are getting a bad reputation right now.
Should countries wait for World Health Organisation (WHO) Emergency Use Listing to use a vaccine in their respective countries or should they go ahead with local regulation agencies’ recommendations to administer vaccines for local populations?
Historically, the major regulations such as the US Food and Drug Administration (FDA), European Medicines Agency (EMA), the UK regulators go ahead and make their own recommendations before the rest of the world. WHO also makes recommendations on top of that. Historically, a lot of the other countries look in the direction of the WHO and these other major regulators. I think that Covid-19 has changed that. What I would suggest is that if a country has sufficient specialists to review the data on safety and immunogenicity, which Sri Lanka definitely does, you should go ahead with that. Covid-19 is terrible but it has also gotten countries to set up their own boards, regulations and committees to review that data. It is high time that we also examine the data among ourselves and make recommendations than wait for other big regulators. If WHO has not discussed and qualified a vaccine yet, say a Russian vaccine, it is okay for a country like Sri Lanka to go ahead with your own guidelines if data has been carefully reviewed, and efficacy and safety is ensured. Because sometimes, the big regulators might not have the priorities we have. A country like Sri Lanka might have access to different vaccine candidates that developing countries have access to.