Have we found a shield against the next covid? We are not even out of this pandemic yet, as we already know that a new global epidemic is more and more likely in the short term. But instead of suffering and running behind the virus as we have had to do for the past two years, we could prepare now for the arrival of this potential new virus. But how do we make vaccines and treatments against pathogens that we do not yet know? The answer to this dilemma may have been found in Singapore, where a team managed to produce antibodies that neutralize not only the coronavirus responsible for Covid-19 (Sars-CoV-2) but also other coronaviruses currently present in bats and other wildlife that have a high chance of causing future pandemics. To better understand this major discovery that could prevent us from a new health and social disaster, Science and the Future interviewed Lin-Fa Wang, director of the Emerging Infectious Diseases program at Duke-National University of Singapore Medical School and author of the study published August 18, 2021 in the New England Journal of Medicine.
Currently, we see that vaccines have trouble effectively neutralizing the different variants of covid, Delta in particular. However, you argue that we could create a vaccine against all these variants and also against other coronaviruses. How would that be possible?
Lin-Fa Wang: Delta and the other variants have shown us that the immune response is very specific and that even the slightest change in the region of Spike targeted by the antibodies can reduce the effectiveness of vaccines. When we are infected, our body makes antibodies to neutralize the virus. But our immune system is very smart, and it’s not going to waste energy producing poorly effective antibodies. Rather, it targets the parts of the virus that are most important for infection, which are usually the parts that interact with cell receptors that allow it to attach to cells (ACE2 in the case of the ovid). So the antibodies produced will mainly block this part to prevent infection. But these parts are also the ones that change most often and the slightest change can decrease the effectiveness of these antibodies. This could be avoided with antibodies that target more conserved parts of the virus, which change less and therefore allow the antibodies to maintain their effectiveness with several variants, or even several species of coronavirus.
And how could we produce these antibodies that target more conserved regions?
When we are vaccinated or infected with a coronavirus, the antibodies generated will mainly target this immunodominant part, which in Sars viruses is the domain that recognizes the ACE2 receptor (RBD for receptor binding domain, editor’s note). What we have seen is that when we are vaccinated against another species of coronavirus after having developed this first immunity, our immune system will produce new antibodies. But since RBD is already covered by already existing antibodies, our body is forced to produce antibodies against other regions of the Spike protein. Regions which are less important for attaching to human cells but which are more conserved and which can nevertheless make it possible to block the virus. And these regions are so conserved in evolution that these new antibodies can recognize a large number of coronaviruses.
How did you get the idea to analyze the effect of this sequential immunity against several coronaviruses?
I was very involved during the SARS epidemic in Singapore in 2003, caused by the Sars-CoV virus, very close to the Sars-CoV-2 responsible for Covid-19. When it was confirmed that this new pandemic was caused by a Sars virus I wondered if the immunity acquired by SARS survivors could neutralize this new coronavirus. This was not the case, because these antibodies were also targeting the RBD domain of the Spike protein which binds to the ACE2 receptor, but it is too different in this new coronavirus to be neutralized by these antibodies. But once vaccinated against Sars-CoV-2, these SARS survivors produced different antibodies, which targeted better-preserved parts of the Spike protein. Antibodies that managed to neutralize all variants of Sars-CoV-2 as well as other coronaviruses present in bats. It was wonderful !
Can we use this new knowledge to create a vaccine against several coronaviruses?
Now the question is can we reverse the process, by vaccinating against another coronavirus after vaccination against Sars-CoV-2? To do this, we are working on a vaccine that will target not only Sars-CoV but also other sarbecoviruses, that is to say viruses of the coronavirus family, of the beta genus and of the Sars subgenus. Within a year, 70% of the world’s population will be vaccinated against Sars-CoV-2. And if we work quickly we could already have this new vaccine, which would therefore serve as a booster against covid and all its variants, but which in addition would protect us from other coronaviruses. It would be the first time that we have created a vaccine against several species of virus, something that we have already tried for influenza or dengue but never succeeded before.
Will we be ready then, if we are ever attacked by a coronavirus again?
Yes, because this same principle could be used to make antibodies to treat patients who have been infected with this potential new coronavirus. Like the monoclonal antibodies produced by Regeneron that were used to treat Trump, but which this time could treat humans against coronaviruses that are not yet in humans. Thus, we are preparing a whole arsenal for this future pandemic, with the vaccine and the treatment in case this vaccine is not sufficiently effective in certain people. This strategy will allow us to get out of the current pandemic, this is the priority, but also to keep ourselves ready for the next one. Sounds like science fiction, but I’m convinced it’s doable.