Experts warn against partial immunity, mutation risks
As India begins its Covid-19 vaccination drive, it must protect against leaving its population with partial or subpar immunity to the coronavirus that may ultimately risk triggering mutations, experts who have tracked the launch of immunisations in the US and the UK have said, advising careful focus on speed as well as accuracy.
Viruses mutate due to what is known as selection pressure and – in addition to evolution within immunocompromised people — this could also happen in case of vaccines if the doses are given in a manner does not to lead to highest efficacy, or if they offer inadequate protection. “We know that the virus mutates... A subpar immune response may give immunological advantage to the virus and it may induce more genetic diversity within the virus,” said Maria Elena Bottazzi, the associate dean, National School of Tropical Medicine at Baylor College of Medicine, in an interview to HT.
Bottazzi was speaking in the context of a debate in the US and the UK on whether to delay the second doses to ensure that vaccine inventories are used up to inoculate as many people as quickly possible – a strategy that may not be scientifically sound.
India has decided not to follow this model, and to give the vaccine at the 28-day intervals recommended by the manufacturers. “Scientifically, it is very clear that you need the doses at the right time to really get a robust immune response with good neutralising antibodies. So if we don’t vaccinate people on time, they might end up with a subpar level of immune response and that could be complicating because we know the virus mutates,” Botazzi said.
“I understand the anxiety of trying to have as many people vaccinated but I think it should be on the basis of how much inventory we have. Yes, vaccinate as many people as possible but you have to make sure that each individual has the required second dose.”
A similar threat is also posed if the vaccines are not as effective. “A partially effective vaccine could drive the evolution of new variants, which would be a serious problem,” said John P Moore, leading virologist and professor at Cornell University’s Weill Cornell Medicine in an interview over email. Concerns over efficacy have surrounded one of the vaccines that India rolled out on Saturday since Covaxin, made by Bharat Biotech, is yet to reach the clinical trial threshold where it can be determined if and by how much the vaccine is able to offer protection from disease.
At the time of its approval, authorities said that it is likely to be a better option in fighting mutations that have been seen in several countries since it uses a whole virion to train the body to recognise the pathogen, instead of just the Spike protein that most other vaccines mimic for an immune response. “There is no reason why an inactivated virus vaccine would automatically be superior to an adenovirus vector vaccine. Only data can show which is better,” said Moore, while adding that such remarks by administration members could be “based on the national origins of the vaccines”. “That has happened in the UK too, where the British government speaks very, very highly of the Oxford vaccine,” he added.
The two experts also said that it is important to ensure that immunisation programmes avoid controversy that could fuel vaccine scepticism. For instance, the approval to a vaccine without efficacy data “was not a good idea”, according to Moore. “It would not happen in the US, or in Western Europe. The Russians and Chinese have done this. I don’t think it’s a good idea, as it could harm public confidence in what they are being asked to take,” he said.
The concerns surfaced on Saturday, when at least two doctors groups – the Tamil Nadu doctors’ association and a group of doctors in Delhi’s Ram Manohar Lohia hospital – indicated they were reluctant to take Covaxin.
Like Covaxin, the Oxford-AstraZeneca vaccine (called Covishield in India), dose also elicited some controversy after its trials were found to have been conducted with unplanned dosing and threw up varying efficacy numbers. However, both vaccines have in early clinical stages have proven safety and an ability to trigger an immune response.
When they cleared the Oxford-AstraZeneca dose, regulators in UK said second doses can be delayed by up to 12 weeks in order to focus on reaching as many people as possible for first shots since even those can provide some immunity. The approach, however, was not part of clinical trials.
The authorities were partly driven by the fast spread of the B.1.1.7 variant of the coronavirus (also known as VOC202012/01), which has been linked to higher infectivity. Following its discovery, several other variants have been found – some of which have raised fears that vaccines may be rendered obsolete.
“We are concerned with any mutation that occurs in the spike or particularly in the RBD (receptor binding domain – the portion of the virus responsible for entering a host cell). There is initial data that is giving us optimism that some of this may not alter the ability of producing neutralising antibodies with the vaccines,” said Bottazzi, whose team at Baylor is also developing a DNA recombinant vaccine with Hyderabad-based Biological E. The vaccine candidate is in Phase I/II trials.
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