Double mutation concerns: COVID-19 vaccines working but studies on to assess potential resistance

While the current upsurge in the COVID-19 caseload does not seem to be triggered by the arrival of new variants of the virus, including three concern-causing strains from the UK, South Africa and Brazil, the aspect of the virus showing double mutations in some parts of the country needs to be watched closely, says Rakesh Kumar Mishra, director of the Centre for Cellular and Molecular Biology (CCMB), a premier Indian research organization based in Hyderabad and focused in the frontier areas of modern biology.

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Speaking to Financial Express Online, he says, these mutations need to be watched closely and studied because they are in the region of the spike protein of the virus, which is also the location that is targeted by most of the vaccines. So, changes there need to be closely watched as there is a risk of the changes that could potentially become resistant to the vaccines.

“We are doing this in the lab at the moment. We are studying in-vitro (in the lab) the infected cells and treating it with the serum of the vaccinated person and then seeing the extent to which it is able to block the growth of the virus – the technical name for the process is in-vitro neutralizing assay.” This may take a couple of weeks at least, he says.

He also explains: “it is to help understand the response to a vaccine and is the best judge to gain clarity on vaccine resistance, which is not a problem at the moment but cannot be ruled out.”

Mishra is referring to the double mutations (E484Q and L452R) seen in 20 per cent of the COVID-positive cases in Maharashtra. “This also means the 80 per cent of the positive cases are not because of the variant with these mutations and therefore clearly they are not the cause for the upsurge of cases in Maharashtra,” says Mishra. At the moment, he says, all we know is the L452R mutant was first seen last year in Denmark in March followed by few cases in California and there were concerns around it, potentially at some point, getting to escape the immune system.

What is also important to note, says Mishra is that in other regions, even if the double mutations are present, they are very small in number. “For instance, variants with double mutations were found only in only 9 cases out of the positive cases in Delhi and just 2 cases in Punjab. Also, there is no report of re-infections related to this variant and this is a good indication that the vaccines may work for this also.”
The concern now, says Mishra, is even if the double mutations, at the moment, do not seem problematic – as apparently data from hospitals and mortality numbers suggest- but whether they remain that way and do not pose a danger of resistance to the vaccine, which has not happened so far, needs to be closely followed.

Part of the problem is that it is in the nature of a virus to constantly undergo mutations and at some stage they may get to start producing a resistance to the vaccine and that must be avoided. It has been a concern that others in the vaccine industry have also been talking about. K V Balasubramaniam, an independent consultant and the former managing director of Indian Immunologicals, says, “the double mutations are a cause for concern though not alarming. The efficacy of the vaccines currently in use against these mutants can be quickly checked with in-vitro neutralization studies and this, supported by clinical evidence on the severity can determine the virus abatement strategies that need to be adopted.”

The Three Variants
The focus of most so far has been on the three troubling variants – from the UK, South Africa and Brazil, but the comforting aspect has been that they are still largely insignificant in terms of numbers though they have been so far seen in few Indian states. For instance, CCMB’s Mishra points out, “the UK variant has been noticed more in some cases out of Punjab followed by travel-related cases in Telangana, the South African variant cases in Telangana followed by Maharashtra and a marginal number of the Brazilian variant in Maharashtra.” The key point still being that since the vaccine is still working, it needs to be seen as the only available defence.

The Rising Caseload
What then explains the rise in cases? “They are apparently on account of more public gathering without adherence to COVID safety protocols – there are election rallies happening. That apart, restaurants, market places and mall are all operational, schools and workplaces are also being opened up, as also the public transport,” explains Mishra with an apparent undertone on the need for caution. He says if adequate precautions are not taken then there is a risk of cases continuing to rise ending up in potential risk of mutations that could develop resistance to the vaccine.