To test its immune response, they gave one primary shot and two booster shots to mice models with a gap of 15 days, after which they found a large number of antibodies generated in the blood serum of the mice. These antibodies were also capable of neutralising the live virus, the team found.
Scientists at the Indian Institute of Science (IISc) Bangalore have developed and tested a novel SARS-CoV-2 virus-like particle that can potentially be developed into a COVID-19 vaccine candidate. To study the SARS-CoV-2 virus, the researchers need to isolate the virus from the samples, create multiple copies of it, and analyse its transmissibility and efficiency at entering living cells.
However, working with such a highly infectious virus is dangerous and requires a Bio Safety Level-3 (BSL-3) lab, only a handful of which across the country are equipped to handle such viruses. To address this problem, the team developed and tested a novel virus-like particle (VLP) -- a non-infectious nanoscale molecule that resembles and behaves like the SARS-CoV-2 virus but does not contain its native genetic material.
Such VLPs can not only be used to safely study the effect of mutations that may arise in SARS-CoV-2, but can also potentially be developed into a vaccine candidate that can trigger an immune response in our bodies, the researchers said. These VLPs can also be used to cut down the time taken to screen drugs that can fight the virus, they said. Saumitra Das, Professor at the Department of Microbiology and Cell Biology (MCB), IISc and his lab has previously shown that VLPs can be used as vaccine candidates to trigger an immune response.
When the pandemic hit, Das and his team began working on a VLP for SARS-CoV-2. They first had to artificially synthesise a VLP with all the four structural proteins -- spike, envelope, membrane and nucleocapsid -- seen in the actual virus. "The main challenge was to express all four structural proteins together," said Harsha Raheja, PhD student at MCB and first author of the study published in the journal Microbiology Spectrum.
SARS-CoV-2 replicates by producing each structural protein separately and then assembling them into a shell containing the genetic material inside to form an active virus particle.
To recreate this, the team chose a baculovirus -- a virus that affects insects but not humans –- as the carrier to synthesise the VLPs, since it has the ability to produce and assemble all these proteins, and replicate quickly. The researchers then analysed the VLPs under a transmission electron microscope and found that they were just as stable as the native SARS-CoV-2.
At 4 degrees Celsius, the VLP could attach itself to the host cell surface and at 37 degrees Celsius (normal human body temperature), it was able to enter the cell. When the team injected a high dose of VLPs into mice in the lab, it did not affect the liver, lung, or kidney tissues, according to the researchers.
To test its immune response, they gave one primary shot and two booster shots to mice models with a gap of 15 days, after which they found a large number of antibodies generated in the blood serum of the mice. These antibodies were also capable of neutralising the live virus, the team found.
“This means that they are protecting the animals,” explained Raheja. The researchers have applied for a patent for their VLP and hope to develop it into a vaccine candidate. They also plan to study the effect of the VLP on other animal models, and eventually humans. The researchers said that they have also developed VLPs that might be able to offer protection against the more recent variants like Omicron and other sub-lineages.
(With PTI inputs)