The Indian Institute of Science said on Tuesday that
researchers led by Raghavan Varadarajan, Professor at IISc’s Molecular
Biophysics Unit, are working towards developing effective vaccine strategies
against two viruses: SARS-CoV-2 and HIV.

In two studies published in the past week, they reported the
design of a ‘heat-tolerant’ COVID-19 vaccine candidate and a rapid method to
identify specific regions on the HIV envelope protein that are targeted by
antibodies, which can help design effective vaccines, an IISc press release
said.

According to Bengaluru-based IISc, the studies were published in the Journal of Biological
Chemistry and the Proceedings of the National Academy of Sciences respectively.

The COVID-19 vaccine candidate contains a part of the spike
protein of the novel coronavirus called the Receptor Binding Domain (RBD) – the
region that helps the virus stick to the hosts cell.

It is being developed by Varadarajan’s lab in collaboration
with Mynvax, a startup co-founded by him and incubated at IISc, as well as
several other institutes.

“When tested in guinea pig models, the vaccine
candidate triggered a strong immune response”, the statement said.

“Surprisingly, it also remained stable for a month at
37C, and freeze-dried versions could tolerate temperatures as high as 100C.”

“Such ‘warm’ vaccines can be stored and transported without
expensive cooling equipment to remote areas for mass vaccination – most
vaccines need to be stored between 2-8C or even cooler temperatures to avoid
losing their potency”, it said.

Compared to newer types such as mRNA vaccines, making a
protein-based vaccine like this can also be scaled up easily in India where
manufacturers have been making similar vaccines for decades, IISc said.

There is another difference between the vaccine candidate
being developed by Varadarajan’s team and many other COVID-19 vaccines in the
works: it only uses a specific part of the RBD, a string of 200 amino acids,
instead of the entire spike protein.

The team inserted genes coding for this part via a carrier
DNA molecule called a plasmid, into mammalian cells, which then churned out
copies of the RBD section.

They found that the RBD formulation was just as good as the
full spike protein in triggering an immune response in guinea pigs, but much
more stable at high temperatures for extended periods – the full spike protein
quickly lost its activity at temperatures above 50C, according to the
statement.

“Now we have to get funds to take this forward to
clinical development, says Varadarajan.

This would include safety and toxicity studies in rats along
with process development and GMP manufacture of a clinical trial batch, before
they are tested in humans.

“Those studies can cost about Rs 10 crore. Unless the
government funds us, we might not be able to take it forward”, he added.

The second study focused on HIV, the virus that causes AIDS,
a disease for which there is no vaccine despite decades of research.

The team, which included researchers from multiple
institutes, sought to pinpoint which parts of the HIVs envelope protein are
targeted by neutralising antibodies – the ones that actually block virus entry
into cells, not just flag it for other immune cells to find.

According to the authors, vaccines based on these regions
might induce a better immune response. To map such regions, researchers use
methods like X-ray crystallography and cryo-electron microscopy, but these are
time-consuming, complicated and expensive.

Therefore, Varadarajan and his team explored alternative
approaches, and eventually arrived at a simpler, yet effective solution.

First, they mutated the virus so that an amino acid called
cysteine would pop up in several places on the envelope protein. They then
added a chemical label that would stick to these cysteine molecules, and
finally, treated the virus with neutralising antibodies.

If the antibodies could not bind to crucial sites on the
virus because they were blocked by the cysteine label, the virus could survive
and cause infection.

Those sites were then identified by sequencing the genes of
the surviving mutant viruses.

“This is a rapid way of figuring out where antibodies
are binding and is useful for vaccine design,” says Varadarajan.

It could also help in simultaneously testing how different
peoples sera samples – the portions of their blood containing antibodies –
react to the same vaccine candidate or virus, he says.

“In principle, researchers could adapt this methodology
to any virus, including SARS-CoV-2”, he said.