New Covid vaccine: IISc Bengaluru creates RS2 that promises to fight current, future variants of the virus

Human antibodies targeting parts of the SARS-CoV-2 spike protein. (NIH Director’s blog)

In a statement released by IISc, researchers emphasised that while current vaccines exhibit efficacy against most SARS-CoV-2 strains, their potency wanes due to the virus’s rapid mutation. After scrutinising various proteins within the virus, researchers selected two parts of the SARS-CoV-2’s spike protein — the S2 subunit and the Receptor Binding Domain (RBD) — to design their vaccine candidate.

The S2 subunit, marked by its high conservation rate, undergoes fewer mutations than the S1 subunit, the primary focus of prevailing vaccines.

Recognising the potent immune response elicited by the RBD, the researchers ingeniously crafted a hybrid protein, RS2, by combining these two crucial components.

The researches then employed mammalian cell lines to assess the hybrid protein’s expression. Nidhi Mittal, a PhD student at MBU and the study’s primary author, said in the statement, “The protein showed very high levels of expression, and I [initially] thought that the experiment was not working properly.” This suggests the potential for large-scale production.

The subsequent tests conducted on mice and hamster models revealed that the hybrid protein not only triggered a robust immune response but also delivered superior protection compared to vaccines containing the entire spike protein.

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Promise of hope

Dr Rajeev Jayadevan, Co-Chairman, National IMA Covid Task Force, appreciated the innovation.

Explaining why this vaccine is promising for protection against newer variants, Dr Jayadevan tells South First, “Unlike most current vaccines that focus on one part of the virus’s spike protein, RS2 targets two parts, making it potentially more effective against new variants. RS2 aims to overcome this by focusing on a more stable part of the virus, while also targeting the part that binds to human cells.”

Researchers from IISc have come up with thermostable vaccine candidate for current and future SARS-CoV-2 variants (Supplied)

Most Covid vaccines are based on the S1 subunit of the spike protein, the part that attaches to human cells. The idea was that neutralising antibodies generated against this part of the spike protein will be able to stop the virus from attaching and entering cells, thus preventing infection.

The S2 subunit on the other hand is located away from the landing pad of the virus, and had, therefore, not been a favourite for vaccine makers.

Unfortunately, the virus has quickly made changes to its S1 subunit, specifically the RBD or the exact part of the spike protein that binds to the ACE-2 receptor of the cell.

This essentially means that the virus changed its lock and we were left holding an older key. So the existing vaccines are not as effective at preventing infections by newer variants.

The rationale of focusing on the S2 subunit is that it is less prone to mutations. Think of it as a more stable lock, which cannot be changed by the virus. Hence, an older key will continue to work.

But the downside is that, by itself, S2 might not generate enough neutralising antibodies that are essential in preventing infection. Therefore, the concept of combining the S2 unit with the RBD came up, and such a vaccine using RS2 (the name given to the combination) was found to be successful in eliciting neutralising antibodies even to newer variants in animal models.

As the virus is continuously making changes and causing cyclical infections among large populations, we need to think of newer ways to counter its immune evasive abilities and this groundbreaking study is a promising step in that direction.

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