Covid-19 vaccines: Not all are equal

A medic administers the first dose of Covishield vaccine to a frontline worker. PTI 

The world cannot return to normal without there being effective Covid-19 vaccines and a vaccination programme.

This has driven a massive vaccination mobilisation programme worldwide in which 200 different Covid-19 vaccines have trials in a hitherto unprecedented timeframe of 10 months. Out of these, 51 are in late-stage development or are being deployed. But how different are they from each other and what is their level of protection?

Immune response

Despite their profuse numbers, all the vaccines have one key goal: to stimulate an immune response to the spike protein found on the surface of the Sars-CoV-2 virus. The spike protein is what the virus uses to gain entry to human cells.

Experts said that there are four ways this can be done. According to GAVI, the public-private global vaccine alliance whose goal is to increase access to immunisation in poor countries, eight vaccines which are currently deployed or in advanced stages of development, use an inactivated virus which is injected directly into the target after it has been made safe.

These are the most conventional forms of inoculations out there. Bharat Biotech’s Covaxin falls into this category.

A spokesperson for Bharat Biotech said that the vaccine works using an inactivated virus whose genetic material has been destroyed so that it cannot replicate but can still trigger an immune response. He added that trials had shown Covaxin had demonstrated a broad spectrum neutralising capability with heterologous Sars-CoV-2 strains.

However, noted virologist Dr Shahid Jameel said that there is no evidence so far that Covaxin will neutralise emerging mutations. He also clarified that an inactivated virus “raises only a very weak cellular immunity, if any.”

In some instances, inactivated virus vaccines are sometimes not immunogenic following activation. For example, an inactivated mumps vaccine only produced short-lived immunity while an inactivated respiratory syncytial virus vaccine caused worse symptoms than the actual vaccine when it was tested in a group of children.

Meantime, another 13 vaccines worldwide are protein-based which inject protein subunits or fragments of protein to trigger an immune response. While this minimises the risk of side effects, it also means the immune response may be weaker. These kinds of vaccines require adjuvants, to help boost the immune response.

Another 14 use nucleic acids which inject modified RNA (or mRNA) from the target virus into cells to create target proteins. Scientists have hailed these as the future of vaccines.

Dr Vibhu Jain, head of commercial marketing and research solutions, Merck (Asia-Pacific), explained once the modified DNA or RNA is injected into human cells, it uses our own cell protein factories to make the antigen that will trigger an immune response. “This is a very different way of vaccine management in comparison to what we were doing in the past,” he said.

According to GAVI, the advantages of mRNA vaccines are ease of manufacture and since the antigen is produced inside our own cells and in large quantities, the immune reaction is strong. The Pfizer and Moderna vaccines are mRNA vaccines, which experts believe represent a promising alternative to conventional vaccine approaches because of their high potency and capacity for rapid development. The flipside is that RNA vaccines need to be kept at ultra-cold temperatures, -70 degrees C or lower, which is a challenge for low- and middle-income countries.

The last category includes 16 vaccines using viral vectors to employ a different genetically engineered virus to produce target virus proteins. In this type is the AstraZeneca-Oxford University AZD1222 inoculation, of which Covishield is the Indian label.

Unlike the tried and tested inactivated vaccine platforms, Dr Jameel noted that the viral vector platform is new. “Human adenovirus-based vaccines were first used against Ebola in 2016. Though not licensed, it was used in an emergency situation to vaccinate 60,000 people in West Africa to quell a two-year Ebola outbreak. There have been no licensed viral vector vaccines till Covid-19,” he said.

The core of the vaccines is an adenovirus virus which causes the common cold, explained Dr Bhojraj Suresh, Pro-Chancellor of JSS Academy of Higher Education and Research in Mysuru where the Covishield vaccine trials were held and where trials for Russia’s Sputnik V viral vector vaccine has just started.

“The viral vector is attenuated or reduced in power, which is then injected into the person. As with nucleic acid vaccines, our own cellular machinery is hijacked to produce the antigen from those instructions, in order to trigger an immune response,” Dr Suresh said.

He added that viral vector vaccines can mimic natural viral infection and should therefore trigger a strong immune response.

The sheer range of vaccines shows that while there may be multiple ways of tackling the invisible foe, it remains to be seen how and when they will actually end the pandemic.