Every time a new strain of coronavirus emerges, COVID-19 drug and vaccine makers reassess their “recipes” to see if they work against an evolving virus like Omicron, which has spread rapidly around the world in just a few days. more than a month.
Since the start of the pandemic in December 2019, the SARS-CoV-2 coronavirus that causes COVID-19 has mutated multiple times, giving rise to different variants, with Delta and Omicron being the most sadly popular. Because most vaccines were designed to recognize the original SARS-CoV-2 protein, or at least parts of it, more mutated variants, such as Omicron, better escape the protection offered by vaccines, although they still prevent serious illness.
Last month, vaccine makers talked about tweaking the formula to have an Omicron-specific vaccine on hand, should the need arise. “But Omicron won’t be the last variant,” says Stephen Zeichner, an infectious disease specialist at the University of Virginia Medical Center. “It’s pretty clear that the virus is still evolving and that a universal COVID-19 vaccine or even a universal coronavirus vaccine is needed in the future.”
(Related: The explanation to nine important unknowns about Omicron)
Since 2020, in preparation for the next deadly coronavirus outbreak (which experts believe is only a matter of time), some scientists have begun developing vaccines that protect against multiple coronaviruses. Many efforts are currently focused on known sarbecoviruses, which include SARS-CoV-1 and SARS-CoV-2, and some SARS-like bat viruses that have the potential to jump from animals to humans.
The first tests in animal models are giving promising results. “The good thing about having these vaccines is that they could deal with possible new variants [del SARS-CoV-2], as well as the next and horrible viruses that jump abroad,” says structural biologist Pamela Björkman, from the California Institute of Technology (United States), which is developing a universal vaccine for some viruses similar to SARS.
Block new variants and future coronaviruses with the potential to spread
Omicron, the latest version of the virus classified as a variant of concern by the World Health Organization on November 26, 2021, has almost 50 genetic mutations compared to the original strain of SARS-CoV-2. More than 30 of them are found on the club-shaped spikes that protrude from the surface of the virus, facilitating its entry into host cells. The spike is also the region of the virus targeted by COVID-19 vaccines to prevent severe disease.
Human coronaviruses were first identified in the mid-1960s and rarely caused serious illness. But that changed in 2002, when a deadly respiratory illness caused by a new coronavirus SARS-CoV linked to cave-dwelling bats emerged in China and spread to 29 countries, infecting nearly 8,000 people and leaving more than 700 dead. A decade later, another new coronavirus, MERS-CoV (emerged in Saudi Arabia and presumably also originating in bats) has infected more than 2,000 people in 37 countries, killing nearly 900 to date. The danger posed by animal-derived coronaviruses became even more evident with SARS-CoV-2, which has caused almost 332 million confirmed cases worldwide and more than five million deaths since its appearance at the end of 2019.
Although shortsightedness and underfunding have hampered the development and testing of these vaccines, recent investments such as the $200 million program (176 million euros) from the Coalition for Innovation in Epidemic Preparedness, a non-profit organization, and the research fund of 31.9 million euros from the US National Institutes of Health, mean that vaccines against pancoronavirus viruses – at least for viruses similar to SARS – could be a reality sooner than many imagined.
One vaccine, multiple coronaviruses
The goal of these vaccines is to generate a broad immune response against multiple coronaviruses and their variants.
The effort that is most advanced is a vaccine developed by researchers at the US Army’s Walter Reed Research Institute, which has been tested in humans as part of a phase I trial. The vaccine, that borrows technology developed to make universal flu vaccines, consists of a soccer ball-shaped nanoparticle with 24 faces decorated with multiple copies of the original SARS-CoV-2 protein. Peer-reviewed research conducted on monkeys demonstrated the ability of the vaccine to generate antibodies that neutralize and block the entry of SARS-CoV and SARS-CoV-2 and their main variants (excluding Omicron, which was not tested) in animal cells. “Repetitive and orderly unfolding of the coronavirus spike protein in a multifaceted nanoparticle can stimulate immunity in such a way that it translates into significantly broader protection,” said Kayvon Modjarrad, a co-inventor of the vaccine, in a statement. Press release. His team is currently analyzing the data from phase I. National Geographic contacted Walter Reed on several occasions for more details, but they declined to comment until the results of the phase I trials were published.
(Related: Why are vaccines still imperfect after decades of research?)
Other universal coronavirus vaccines target a genetically and structurally similar, slow-evolving region of viruses (where antibodies bind as part of the body’s immune response to a foreign invader) or, in addition, the immune cells of the virus. body, called T cells.
Zeichner, for example, is targeting the fusion peptide region, which is part of the coronavirus spike protein that helps the virus enter host cells, to develop a vaccine against all coronaviruses. “It is highly conserved among all the coronaviruses,” he says. “It doesn’t mutate much.” Together with colleagues, he tested a proof-of-concept vaccine using a SARS-CoV-2 fusion peptide and early results indicated that in pigs the vaccine provided some protection against a different coronavirus, called porcine epidemic diarrhea virus, which does not infect humans. His team is now collaborating with researchers from Virginia Tech University and the International Vaccine Institute in Seoul (South Korea) to continue developing and testing the vaccine against different variants of SARS-CoV-2 and other coronaviruses.
Björkman and colleagues, for their part, focus on a more specific target: the spike protein’s receptor-binding domain (RBD). It is the region of the spike to which most antibodies bind to prevent SARS-CoV-2 from entering the host cell; it is also the region in which mutations occur, giving rise to variants. For the vaccine, they used RBD proteins from up to eight viruses (including the original SARS-CoV-2 and other SARS-like coronaviruses isolated from bats) that were fused into a 60-sided nanoparticle. By injecting this vaccine into mice, Björkman and his colleagues discovered that the animals produced various antibodies, which in follow-up experiments blocked infections caused by several SARS-like viruses, including coronavirus strains not used to create the vaccines.
For Björkman, this suggests that the immune system of animals could be learning to recognize common characteristics between coronaviruses and that his mosaic vaccine, with selected pieces of multiple viruses, could be useful when new viruses similar to SARS or new variants of SARS emerge. SARS-CoV-2. His team is preparing to test the vaccine in humans.
Vaccine researcher Kevin Saunders of the Duke Human Vaccine Institute in North Carolina is also targeting RBD, but a very specific part of it, to make a vaccine against a similar virus that of SARS. When the pandemic began in early 2020, Saunders and his colleagues began searching for antibodies that would inactivate SARS-like viruses. They examined the antibodies present in frozen-stored cells from an individual who recovered from SARS virus infection and from another individual previously infected with COVID-19.
They identified a potent antibody dubbed DH1047 present in the cells of both patients that could block infections into which mice had been injected with various human and bat coronaviruses, including SARS-CoV-2 variants. Further examination revealed that the antibody bound to the same small section of the RBD spike protein in different coronaviruses, which became the target of the vaccine.
By injecting monkeys with multiple copies of this RBD fragment from SARS-CoV-2 fused to a nanoparticle, Saunders and colleagues demonstrated the ability of the vaccine to protect not only against SARS-CoV-2 but against other coronavirus infections. The team is now testing different interactions of this nanoparticle vaccine by introducing RDB sections from other coronaviruses to amplify the host’s immune response.
Meanwhile, scientists are also trying to figure out how these vaccines might cover not only SARS-like viruses, but also MERS and other coronaviruses further afield. “The sequence diversity and structural differences between coronaviruses that fall into different groups is going to be challenging,” says Saunders. Some scientists propose a different vaccine for different families of coronaviruses.
However, the need for a vaccine against the pan-SARS-type coronavirus cannot be ignored for now. “We don’t think of it as ‘this will be great to have for the next pandemic’ anymore,” says Saunders. “We’re thinking of this as a great tool to stop this pandemic.”
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