HomeLifestyleHealth & FitnessScientists find new way that triggers strong immune reaction against COVID-19 without...

Scientists find new way that triggers strong immune reaction against COVID-19 without side effects

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Currently, 84 percent of COVID-19 vaccines authorized in the United States are virus-based vaccinations: they contain inactivated or attenuated viruses that stimulate the immune system to begin producing antibodies. Although they are helpful, they carry the risk of reactivation, allergic reaction, and other adverse effects.

Vaccines can display a viral protein that induces an efficient immune response without containing the rest of the virus, so avoiding these adverse consequences.

This, however, may result in a reduced response, as the virus proteins are not as densely packed and do not exhibit the same repeated pattern as the complete virus.

In this new study, published in PLOS Pathogens, the team developed a novel form of vaccination that mimics the virus’s dense antigen display and repeating patterns in order to boost antibody development without causing harmful consequences.

They developed a vaccine that generates a fivefold increase in neutralising antibody production compared to a simple viral protein vaccination by creating a protein scaffold that presents multiple copies of the RBD of the SARS-CoV-2 spike protein.

Early in the investigation of SARS-CoV-2, it became clear that a critical factor in the recent outbreak’s increased virality and mortality than other coronaviruses was the virus’s stronger affinity for the human cell surface receptor angiotensin-converting enzyme 2 (ACE2).

The RBD S1 binds to human cells via this cell surface receptor. Although it has shown promise as a vaccination target, this domain is frequently concealed within the spike to evade the immunological response.

To elicit a sufficiently potent immune response to confer functional immunity, a lumazine synthase with an N-terminal protein was being used. When purified, a tag was used as the backbone for the virus-like protein because it spontaneously organized into a functional shape.

After establishing that the SARS-CoV-2 S1 subunit (with a C terminal Fc tag) would attach successfully to the lumazine synthase structure, the scientists purified the complex using gel-filtration chromatography. They noticed that the structure retained its spherical shape while developing a surface similar to that of SARS-CoV-2 and other nanoparticle-based vaccinations.

Finally, incubation of this complex with mouse serum demonstrated that the S1 subunit domain retained not only it’s binding to ACE2, but also its attachment to the virus-like nanoparticle. Two vaccination variants were created: one using mammalian cells to synthesize the lumazine synthase and another using bacterial cells to synthesize the lumazine synthase.

In preliminary mouse tests, the novel vaccination triggered the production of five times the number of S1 subunit RBD antibodies and resulted in animal sera more successfully inhibiting virus entrance into the cell via ACE2 binding.

These results persisted across time, with no change on days 10, 40, or 70. Further research revealed that animals treated with the virus-like nanoparticle were protected against lung damage and acute respiratory distress syndrome when compared to mice vaccinated with a placebo.

Perhaps more significantly, the vaccine’s enhanced efficiency against produced pseudoviruses indicates that it will continue to be successful against the increasingly lethal SARS-CoV-2 strains.

The study authors are hopeful that further testing of the vaccine can begin soon. Increased efficacy against SARS-CoV-2 variants in comparison to existing vaccinations may contribute to the global recovery from the pandemic and prevent more deaths.

However, the bioengineering technique used to create the virus-like nanoparticle has some drawbacks: the Fc tag on the nanoparticle may interact with receptors on some immune cells, impairing immunogenicity, and the attraction between the Fc tags on the nanoparticle and the protein A tags on the viral proteins may eventually result in viral protein displacement.

Despite this, the vaccination has been found to provide nearly complete protection in mice and has the potential to become a significant tool in the fight against COVID-19.

Image Credit: Getty

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