Analysis of coronavirus mutations leads to potential universal vaccine against Covid

Research into the different mutations suffered by the coronavirus over the past three years has led to the development of a universal vaccine candidate against Covid.

The formula, called S_pan (S protein S or spike used by the virus to invade cells and pancoronavirus, or universal coronavirus) contains the main changes that occurred in Sars-CoV-2 that affected the effectiveness of vaccines available so far, especially after the emergence of new ones more infectious strains or with greater immune escape.

When tested in mice in the laboratory, the formula was successful in inducing antibodies against ten variants of concern (or VOCs, for its acronym in English) that have emerged in recent years, including alpha, gamma (from Manaus) and delta.

The immunizer under study also offered a greater protective response in mice that had received two doses of vaccines formulated against the original Wuhan strain (or “wildtype”, also called the wild form), thus enabling its use as a booster dose in the future.

The article describing the discovery was published this Wednesday (4) in the scientific journal Science Translational Medicine and is the result of a collaboration between researchers from Wuhan University, the Wuhan Institute of Biological Products and the Chinese Center for Disease Control and Prevention.

To arrive at a universal vaccine formulation, the scientists analyzed 11,650,487 coronavirus sequences from the National Center for Biotechnology Information (NCBI) database deposited up to February 28, 2021 (that is, before the emergence of delta and omicron). Of the total, 2,675 protein S sequences were studied to create a phylogenetic tree of the virus in its region with the highest mutation frequency.

With this, the researchers observed two main evolutionary “paths” of the virus: one of greater transmission (mutations in the S protein or in the region of connection with the receptor in the host cells that confer greater transmission capacity) and less immunological escape; and another with less transmissibility but high immune escape.

In the first group would be the alpha, lambda (which appeared in Peru), delta and D614G variants, the first variant of the virus to appear in August 2020.

In the second group would be the gamma, from Manaus, and the B.1.525 (or eta), which was identified in New York and Europe in early 2021.

The only variants that seem to escape this evolutionary path are beta and omicron, both initially identified in South Africa and which have high transmission and also high antibody escape.

Considering the mutations of all these variants, the scientists created an antigen (roughly speaking, the structure inserted in vaccines that mimics the pathogen against which an immune response is to be produced) that would be equally effective against mutations that induce high transmission and high immune escape. .

With the formulation, they injected the potential vaccine into mice and then extracted blood samples to assess its action. The result was high protection in mice against all variants, even those that appeared after the development of the study (such as delta and omicron).

Despite being promising, the study still has some limitations, the main one being that the experiments were carried out in vitro from the blood collected from mice that were immunized and tested against the strains, but it is still not possible to know for how long these antibodies will last. offer protection in life. Furthermore, further testing in other animal models, such as monkeys, before human trials is needed.

NATURAL SELECTION

According to virologist and professor at the Faculty of Medicine of São José do Rio Preto, Maurício Nogueira, who was not involved in the study, the search for new antigens when an infectious virus has a high mutation rate is not uncommon in vaccine research.

He explains that this is what happens every three or four years with the vaccine against the influenza virus, which causes the flu. “The biological process that explains the escape of the ancestral vaccine by the circulating virus is the ‘antigen drift’ [deriva] and the ‘antigen shift’ [troca]. The first is the accumulation of mutations in the virus that ends up, naturally, making the vaccine in use and the virus in circulation distant from each other, and therefore an update is necessary. The second occurs when there is a sudden change in the genetic sequence of the virus, causing outbreaks, as happened with H1N1 in 2009”, he says.

In the case of the coronavirus, as it is still very recent, Nogueira assesses that we have not yet reached a balance between the virus and vaccines. “When there is high vaccination coverage, this race between virus and vaccine occurs slowly, but we still have many places with low vaccination coverage”, he says.

The virologist recalls that mutations are a natural and constant process of the virus. Mutations often end up being selected by similar pressures leading to what is known as convergence: different lineages that present the same mutations, as is the case of BQ.1 and the omicron subvariants identified in China.

“The virus will replicate more in environments with a greater number of susceptible people, which increases the possibility of emerging variants that will be selected”, he says. “What is still expected from the coronavirus until the endemization process is the occurrence of sporadic outbreaks when new variants appear and a selective pressure from them for those that manage to escape more from vaccines”, he concludes.