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Coronaviruses are a group of related RNA viruses that are known to cause respiratory tract infections in humans and other animals. Although all viruses mutate while replicating and infect host cells, RNA viruses are particularly unstable, which means they are more prone to mutation during replication.
Most viral mutations are minor and have no impact on the virus or the disease it causes. However, multiple mutations can lead to the emergence of a new variant of a virus, and sometimes these new variants may be more transmissible or deadly, as they can better evade the immune system.
The appearance of variants of SARS-CoV-2
SARS-CoV-2, the coronavirus that caused Covid-19 and wreaked havoc around the world over the past year, has also been mutating.
There are now three worrying new variants of SARS-CoV-2 circulating globally. The first was identified in the UK in September by genomic sequencing and has been named B117. Another variant, known as 13551, was discovered in South Africa in October and contains many of the same B117 mutations in the peak, although it arose independently. The third, which is called P1 and is believed to have emerged in Brazil in December, contains many mutations similar to the other two variants.
All three variants are believed to spread more easily and quickly than other SARS-CoV-2 variants, but there is no evidence that they are causing more serious illness or higher death rates. However, it is possible that these variants escape the immune system and therefore mean that those who have previously contracted Covid-19 are susceptible to reinfection.
The threat of these variants has caused many countries to close their borders to stop the spread of these highly virulent and communicable Covid-19 variants. For example, the UK has closed its borders to South American countries and Portugal, while many countries in Europe have banned visitors from the UK.
This situation has also raised concerns that the approved Covid-19 vaccines, which are the main global exit strategy from the pandemic, may not be effective against these emerging variants. Fortunately, for these mutations and variants, this is likely not the case for the Pfizer / BioNTech Covid-19 vaccine. On January 20, Pfizer and Biotech
It is unclear whether the other approved vaccines, including the Moderna and AstraZeneca / University of Oxford vaccines and Russia’s Sputnik V, are still effective against these three viral variants.
Despite some promising signs, the world is not out of the woods yet. It remains possible that these variants continue to mutate, or that other variants emerge, to be resistant to vaccines.
Enter Next-Generation Vaccines to Address Covid-19 Variants
When SARS-CoV-2 appeared on the world stage in early 2020, many pharmaceutical groups jumped into action. After receiving the genetic code for the emerging coronavirus from researchers in Australia and China in mid-January, these companies signed agreements and began applying existing technology, often used for earlier coronaviruses like SARS and MERS, to develop vaccines targeting the protein S used by SARS-CoV-2 to infect human cells.
Thanks to these efforts, within nine months of the onset of the pandemic, three vaccines had completed Phase III trials and began to be approved worldwide.
Given the likelihood that SARS-CoV-2 will mutate and new viral variants emerge, other vaccine developers took their time and decided to look beyond the obvious target, the spike protein (S), when designing their Covid-19 vaccines. Two examples of companies with next-generation vaccines designed to better resist the new variants are Vaxart, based in California, and OSE Immunotherapeutics, of France.
Beyond Protein S: Vaxart Oral Covid-19 Vaccine
Vaxart Founder and Chief Scientific Officer Sean Tucker says: “We know from history that coronaviruses can be re-infected every two to five years and that is generally not due to decreased immunity, but rather to strains mutating to avoid pre-existing immunity. . ”
Tucker adds that during the spring, when the pandemic spread, it became clear to him that “protein S would probably be very susceptible to mutations.” Therefore, Tucker explains, when applying its oral vaccine technology to the Covid-19 pandemic, Vaxart decided to also include the nucleocapsid protein (N), an area “historically highly conserved among… coronaviruses” in its VXA-CoV2 vaccine. 1. .
“The idea was that as S mutated, we could still elicit a strong T cell response against N proteins” to protect against emerging variants, Tucker says. This concept paid off in Vaxart’s ongoing Phase I trial, in which orally administered VXA-CoV2-1 was found to activate strong T-cell responses against S and N proteins. Now Vaxart needs to continue collecting data to confirm that VXA-CoV2-1 remains effective against variants as they emerge and continue to mutate.
As it is an oral vaccine, Vaxart’s VXA-CoV2-1 could also overcome one of the other challenges that first-generation vaccines face: logistics. Vaxart CEO Andrei Floroiu said in a statement: “Our room temperature stable oral tablet vaccine has the potential to alleviate many of the problems associated with cold chain dependent distribution and administration of injectable vaccines and may make herd immunity more achievable easier to vaccinate more people faster. ”
Covid-19 vaccine with 11 OSE targets
Similar to Vaxart, OSE Immunotherapeutics noted that all first-generation vaccines were targeting the same antigens on protein S, according to the company’s chief scientific officer, Nicolas Poirier. Poirier was concerned because “we know that when you have a high immune response against the same antigens you have a pressure selection effect, which could favor the appearance of variants or mutations”, as well as the fact that protein S is prone to mutation.
OSE decided to focus on “targets that are not exposed to the body, as they are inside the capsid of the virus,” Poirier notes.
To decide which epitopes, or small protein fragments, to target with its vaccine, OSE examined “the memory response of T lymphocytes in symptomatic and severely convalescent patients” and 46,000 SARS-CoV-2 sequences to avoid mutation hot spots. .
OSE used its Memopi technology to establish 11 different targets that lie outside these high-mutation regions and are naturally immunogenic in humans for inclusion in its CoVepiT vaccine. These targets focus on areas of SARS-CoV-2 that include S, M, N, and nonstructural proteins and are also intended to confer not antibody-based immunity, but a long-term lymphocyte response to SARS-CoV-2.
As CoVepiT moves toward the start of Phase I studies, Poirier notes that OSE continues to regularly screen hundreds of thousands of SARS-CoV-2 sequences to verify that there were no mutations in the regions targeted by the vaccine.
This vaccine design approach also means that even if one of the variants were mutated to compromise the S-targeting epitopes of OSE, “there are still 10 other targets designed to elicit a T-cell response against SARS-CoV-2,” he says. Poirier. “Outside of Spike, no SARS-CoV-2 mutation has been observed in our other 10 targets.”
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