The quest for a COVID-19 vaccine



Image: TheDigitalArtist/pixabay

​The novel coronavirus has brought the world to a standstill, literally. The outlook for the near term is sobering. In the absence of successful treatments or vaccines, the number of infections ‒ already past two million now ‒ may continue to climb. Hospitals are facing serious shortages of critical medical supplies. Governments are scrambling to staunch the economic fallout from extended lockdowns.

The silver lining, however, is the incredible pace at which vaccines are being developed. If things go as planned, a vaccine may be ready in 12-18 months, much sooner than the years or decades that it usually takes.

Vaccines work by presenting a piece of or a weakened form of the disease-causing agent ‒ the virus in this case ‒ to our body’s immune system, which flags it as a foreign invader and produces antibodies against it. The immune system has a long memory; when the actual viruses show up, it remembers what they look like, and quickly produces antibodies to quell them.

About 70 vaccine candidates for COVID-19 are currently in various stages of development. New technologies are also being explored to speed up production.

RNA vaccines

Just two months after the genetic sequence of the novel coronavirus was published, a healthy volunteer received the first shot of an experimental vaccine built using a tiny strip of artificial genetic material called mRNA.

This vaccine mimics the mRNA molecule found in our cells ‒ a key component of protein synthesis ‒ and carries the blueprint for making proteins that are part of the virus structure. Once the vaccine enters our cells, the protein-making machinery can ‘read’ it and start churning out viral proteins, which can then be displayed on the cell surface for immune cells to find and commit to memory.

mRNA vaccines can be rapidly produced in the lab, and are less expensive to make than traditional vaccines, because they do not need complex manufacturing processes. They do not carry bits of the virus itself directly into our body, only the ‘instructions’ for our cells to make the viral proteins. Unlike DNA, there is no risk that they will be incorporated into the host genome, so they are likely to be safe. They can also be adapted for any type of protein.

While much research has been done on how to synthesize, stabilize and deliver mRNA into cells, no vaccine has made it to the market so far. There is also concern that it is being tested too soon in humans, before extensive animal testing. “It is a very promising modality, but as of now there isn’t enough safety data on the specific constructs being tested to really be sure,” says Raghavan Varadarajan, Professor at the Molecular Biophysics Unit, Indian Institute of Science (IISc).

Protein subunit vaccines

Varadarajan’s lab is working with an IISc-incubated startup called Mynvax to develop another type of vaccine called subunit vaccine, which directly uses the virus’ spike protein or portions of it. These spike proteins stud the surface of the virus like a halo, and help it enter our cells by latching onto a receptor on the cell membrane.

Structure of SARS-CoV-2 spike protein (Image: Wikimedia commons)

To test if a protein or protein fragment can make a promising vaccine, it is first injected into animals in the lab, which produce antibodies against it. Sera, which are portions of blood containing the antibodies, are extracted from the animals and tested against the virus or its components at different dilutions, to see if they are capable of blocking infection in cell culture. “The highest dilution at which infection is still significantly inhibited is an indication of how potent the vaccine is,” says Varadarajan.

Mass production of protein-based vaccines is quite feasible, because companies have been making them for decades. However, they require stringent purification processes, which can drive up the cost. “We also need to see how to make them more them in some way so that the amount of antibodies produced is sufficiently high to protect against infection in most people,” says Varadarajan.

Other approaches

And then there are tried-and-tested types that use living but weakened forms of the virus, called live-attenuated vaccines. These are usually made by growing generations of the deadly strain in the lab, and carefully selecting mutants that can multiply inside our body ‒ just enough to incite an immune response ‒ without causing infection. Often, a single dose is sufficient for lifelong immunity. However, such vaccines pose some risks for people with compromised immune systems. The weakened virus may also very rarely be able to revert to its lethal form.

Other vaccine types are also being explored. China’s CanSino Biologicals, for example, is using a modified common cold virus as a carrier to deliver the spike protein gene; this will soon advance to Phase II clinical trials.

In India, several companies are trying to develop related vaccines. Serum Institute of India is working with a US-based firm to develop a live-attenuated vaccine. Bharat Biotech has a tie-up to modify a newly developed influenza vaccine to incorporate spike protein genes. And Zydus Cadila is working on a retrofitted measles virus as well as a DNA-based vaccine.

But the quest does not end with making a vaccine candidate. Rigorous safety and toxicity tests will need to be done. Substantial funding will be required to manufacture and distribute it. Potential side-effects also have to be carefully monitored. A dengue vaccine, for instance, had to be pulled from the market even after large-scale clinical trials, because it was found to enhance disease in some cases.

Sustained efforts are also needed. During the SARS and MERS outbreaks, there were frantic attempts to develop vaccines, which soon tapered off after the outbreaks died down. “There has not been as much development for those as there will be for this virus,” says Varadarajan. “I don’t see it disappearing soon.”

Ranjini Raghunath is a Communications Officer at the Office of Communications, Indian Institute of Science (IISc), Bengaluru.