Scientists from Duke-NUS and the National Centre for Infectious Diseases (NCID) found that 2003 SARS survivors who have been vaccinated with the Pfizer-BioNTech mRNA vaccine produced highly potent functional antibodies that are capable of neutralising not only all known SARS-CoV-2 variants of concerns but also other animal coronaviruses that have the potential to cause human infection. This finding, published in The New England Journal of Medicine, is the first time that such cross-neutralising reactivity has been demonstrated in humans, and further boosts hopes of developing an effective and broad-spectrum next-generation vaccine against all types of SARS-causing beta-coronaviruses.
In its first podcast episode, MEDICUS speaks with Duke-NUS Professor Wang Linfa from the Emerging Infectious Diseases Programme about the discovery, what SARS-causing beta-coronaviruses or sarbecoviruses are and the hope this study offers.
Nicole Lim, Host: Hello and welcome to MEDICUS – the Podcast. I’m Nicole and with me is science communicator, Dr Lekshmy Sreekumar.
Dr Lekshmy Sreekumar, Host: Hi everyone.
Lim: And we’re here to talk about something extremely exciting that is happening at Duke-NUS...
Sreekumar: Yes, Wang Linfa, Duke-NUS’ very own batman, has a paper out in the New England Journal of Medicine, in which he along with a team from NCID found that people who had SARS back in 2003 and are now vaccinated against COVID actually produce neutralising antibodies that can attack not just SARS and COVID, but all kinds of sarbecoviruses.
Sreekumar: (laughter)… Sar-be-co-viruses.
Lim: Sar-be-co-viruses. I’ve never heard of those. What are they?
Sreekumar: Sarbecovirus is the name of a diverse group of coronaviruses. But like you, Nicole, it was a term that I was not familiar with. So, I spoke to batman himself…
Wang Linfa: Hi everybody, I’m Wang Linfa and I’m professor in the Programme for Emerging Infectious Diseases at Duke-NUS Medical School in Singapore.
Sreekumar: Hi Professor Wang, thanks for joining us. So, what are sarbecoviruses and why did you choose to focus on this specific group of coronaviruses?
Wang: In virology, we give a family tree to all viruses. So, coronavirus is a family and below the family, we have the genus. So, we have the Alpha, Beta, Gamma, Delta genus. And in the Beta genus, we have SARS-CoV-1, SARS-CoV-2, and the MERS coronavirus and others. And SARS-CoV-1 and SARS-CoV-2 belong to a group called sarbecoviruses, basically SARS-beta-coronaviruses.
And these have some commonality because they all use the same molecule on our cell surface called the ACE2 molecule as a gate to enter our cells, replicate and do all the nasty things that can cause severe disease and, sometimes, death. We now know that this group of viruses is highly dangerous because they’re very transmissible among humans and can cause lethal disease. So, what we’re worried about is that SARS-3 and SARS-4 will also come from this sarbecovirus group.
Sreekumar: So, how is it different from the current pan-COVID vaccine candidates being developed to boost our immunity to fight different variants?
Wang: Our first-generation vaccines target the protein that comes from the original virus, and we are largely protected with that vaccine. But some people can be infected by variants. This is called vaccine breakthrough infection. Pan-COVID-19 vaccines right now are trying to be booster shots. These are vaccines developed against, for example, the Beta variant. If you receive that booster shot on the background of already having the first-generation vaccine, then we expect you will be protected against all the variants we know. That’s a pan-COVID-19 vaccine. We used to have Alpha, then we had Beta. Now the Delta variant is the most concerning, so there is a possibility we have variants XYZ still to emerge. And then on top of that, we could have other sarbecoviruses jump to humans and cause SARS-3, SARS-4.
Sreekumar: And in this study of people who were infected with SARS and are vaccinated against COVID, what did you find?
Wang: Seventeen years ago, I was involved in SARS research and January last year, I was in Wuhan, so I realised that this COVID-19 virus is very close to SARS-1. So, on 18 January, I flew back to Singapore and the first question I asked myself and the national research team was: ‘Is it possible that SARS-1 survivors contain antibodies which can neutralise SARS-2?’ If that’s the case, then we have a therapeutic in convalescent plasma. Unfortunately, their antibodies did not cross-neutralise SARS-CoV-2.
So, 18 months later we had another opportunity to ask, ‘When SARS-CoV-1 survivors receive the COVID vaccine versus somebody like me—I call myself naive because I have not been infected by either SARS-1 or SARS-2—if we compare the antibodies in our bodies are they different?’
To our pleasant surprise, there’s a huge difference. Because when SARS-1 survivors are vaccinated, they produce a much better antibody response, not only the level of antibodies but also that the breath of them. They have antibodies that can fight different sarbecoviruses. And how do we know that? Last year, we invented a surrogate virus neutralisation test, called cPassTM. That was a single test against a single virus, the original SARS-CoV-2 virus. Since then, we have improved the test and we have now what we call a multiplex, meaning that we can do the same test, use the same human sera sample against ten different sarbecoviruses.
Using the multiplex test, we demonstrated that when SARS-1 survivors are immunised with the SARS-CoV-2 vaccine, they produce antibodies that are capable of fighting every sarbecovirus that we included our study.
Sreekumar: That’s interesting. So, these antibodies are bit like a Swiss army knife?
Wang: I think you can think of them as a Swiss army knife. When they see a different sarbecovirus, they can just mobilise that part of the antibody arsenal and then fight the viruses.
Sreekumar: But SARS has disappeared, so how can those of us who are vaccinated or had COVID get wider protection against all kinds of sarbecoviruses?
Wang: What we want, first of all, is to focus on SARS-2 vaccination of the population and then follow that up with a booster vaccine, called third generation coronavirus vaccine or 3GCoVax. Using a 3GCoVax, we try to mimic that process, so that your body can fight not only the variants we know and the emerging variants that we don’t know, but even potentially emerging sarbecoviruses that could become SARS-3 and SARS-4 in the future.
Sreekumar: Oh, that’s great. So, you see, Nicole, we should all be excited by this discovery that antibodies can be taught not just to fight SARS-CoV-2 but all kinds of coronaviruses.
Lim: Thanks, Lekshmy, for catching up with batman. Looks like he’s on a mission that will benefit us all. This was MEDICUS – the Podcast. We hope you enjoyed the show.
This episode was produced by Nicole Lim and Dr Lekshmy Sreekumar.