Call it a booster or precaution dose, but with the launch of its latest vaccination programme on January 10, India continues its battle against Covid-19. And it couldn’t have started any sooner, for the highly contagious Omicron variant is driving up the number of cases in the pandemic’s third wave. Close to 57.5 million people are eligible for the third shot, among them 27.5 million people above the age of 60, 10 million healthcare workers and 20 million frontline personnel. Eligibility can be checked on CoWIN, and a prior consultation with doctors is advisable.
That done, all one needs is a mobile number or an identity card to take the third shot. A booster dose is meant to elicit a robust antibody response. However, while the Government of India-approved ‘prevention’ doses are vital for the vulnerable, virologists and other medical researchers also believe it is crucial to assess the cross-immunity generated by mixing available vaccines. They recommend that safety profiles be well established before administering different vaccines as prevention doses.
Graphic by Tanmoy Chakraborty
Apart from Covishield and Covaxin, seven other vaccines, including an mRNA vaccine that is easier to produce and quick to launch, have been approved. The mandatory two doses are expected to be given to all in the country in the next 4-5 months. The vaccines seem remarkably effective against all variants in preventing hospitalisation and saving lives. But long-term data on their use is not available yet. The vaccines have been approved on ‘reasonable basis’ on information available in little over a year with Emergency Use Authorisation (EUA).
“None of the vaccines, including the mRNA vaccines, are protecting against infections,” says Dr Rakesh Mishra, director at the Tata Institute for Genetics and Society, Bengaluru. “The advantage with the third wave is that we have very large sero-positivity, of about 80 per cent or more, and many of the vulnerable enjoy a fairly high degree of immune protection with one or two doses, though they may not be protected against infection.”
“If we do not change our mindset from that of the dreaded Corona to a benign cold, it will be a greater challenge. As a population, we will not be able to face it”
– Dr Jayaprakash Muliyil, Chairman, Scientific Advisory Committee, National Institute of Epidemiology
Though research data is scanty, there is enough to show that antibodies decline six months after taking two shots of a vaccine. Hence the need for a booster dose. However, as Mishra points out, “Boosters have limited value, which is why they are called precaution doses. We do not have data to tell us if those taking it enjoy a specific percentage of protection. It provides a marginal top-up of antibodies, but we cannot say anything with certainty yet. To call it boosters, we should have data on how exactly it works. We do not have it now. What we know is the vaccines are safe and it is good to provide extra protection to the relatively more vulnerable.”
COCKTAIL CONUNDRUM
Though the Centre has for the moment ruled against mixing vaccines, a mixed dose of Covishield and Covaxin can certainly boost the spike protein-neutralising antibodies and enhance vaccine effectiveness even against Omicron, says Dr D. Nageshwar Reddy, founder-chairman of the Asian Institute of Gastroenterology (AIG) Hospitals and its adjunct Asian Healthcare Foundation. A study done by AIG apparently confirms this, as none of the participants showed any adverse effect. “When the first and second doses were from different vaccines, the spike protein antibody response was four times higher than that after two doses of the same vaccine,” he says. Spike protein-neutralising antibodies kill the virus and reduce overall infectivity.
The AIG study also revealed that 87 per cent of the participants—who were not vaccinated and had never tested positive— had Covid antibodies. “This means our population might have developed significant antibodies against Covid because of the huge Delta wave we endured,” says Reddy.
Epidemiologists, however, are sceptical about implementing the third dose for vulnerable groups as the mainstay of India’s vaccination strategy, saying it has limited additional value. Overcoming vaccine hesitancy and ensuring people take the first and second vaccine shots should remain the driving force, they believe. Many countries like the US, UK and Germany are offering booster doses, even permitting mixing of vaccines to top-up anti-bodies, for extra protection.
“Running an effective vaccination programme requires adopting a holistic approach,” says Mishra. “If given a choice, I would first vaccinate all individuals on the planet with two doses and only then think of the third dose. That would be a bigger assault on the virus. It would reduce the infection and we would have to tackle fewer new variants and their spread.”
Policymakers too are reluctant to experiment with the cocktail strategy owing to the risks involved despite health specialists pushing for it. Hence the government’s attempt to stick to its original target of 10 million vaccinations a day despite distribution and vaccination constraints, and to cover all adults and those in the 15-18 age group before the end of summer this year.
OMINOUS OMICRON
What is most worrying about Omicron is its infectivity. Many do not even get to know whether they are infected or not, especially as the virus mimics flu symptoms. The younger age group (3-15) are reckoned as carriers, contracting the infection without showing symptoms and warding off the illness with their stronger immunity. Studies on which vaccines best suit them are yet to be done. With milder symptoms, many do not even get tested. This gives the virus more opportunity to change and emerge in new avatars, taxing healthcare systems and introducing a fresh loop in the pandemic. Masks thus remain the most effective protection against its spread. “Omicron is doubling in barely two days,” says Dr Jayaprakash Muliyil, chairman of the Scientific Advisory Committee, National Institute of Epidemiology. “It is faster and, in that sense, superior to Delta. It also shows scant respect for previous infection or vaccination. All that is available is based on the Wuhan virus. So a multiple booster against Omicron will not work.”
Studies so far show that this variant does not affect the lungs like its predecessors and is confined mainly to the upper respiratory tract. The pathogenicity is lower and the virulence slower. Studies from South Africa show that it is highly immunogenic and also has cross-reactivity for the previous infection. It is an accomplished immunogen. It produces immunity against itself and the speed with which it went up and came down in South Africa suggests it may not be as dangerous as Delta. “If we do not change our mindset from that of the dreaded corona to a benign cold, it will be a greater challenge and as a population we will not be able to face it,” says Muliyil, emphasising that those being hospitalised are largely the previously unvaccinated. Moreover, virus positivity is not the way to treat cases anymore. He suggests thinking afresh in terms of illness, begin treating it and confirming the presence of the virus. Vaccination is not intended to load up the body with antibodies. It is intended to sensitise the immune system; once sensitised, it will fight back any time it is asked to do so.
VACCINE PROSPECTS
Vaccine-makers maintain that inoculation is the only immunity and are, therefore, working on newer iterations for emerging situations depending on how the virus mutates. They rule out developing a single vaccine to treat all variants. Bharat Biotech, awaiting the outcome of studies, feels that a three-dose vaccine will be effective against Omicron. “The depth of science is bettering innovation in India,” says CMD Krishna Ella, who also plans to register a patent. “We are close to unveiling a nasal vaccine that will provide immunity and also help break transmission.” He believes that apart from Covid-19 turning endemic, variants will continue to exist and be treated like influenza, with one or the other variant playing up in one or the other region every year.
Last month, India granted EUA to two new Covid vaccines—Corbevax and Covovax. Corbevax was developed by the Hyderabad-based biopharmaceutical firm Biological E, along with Baylor College of Medicine and Dynavax Technologies in the US. It uses a recombinant protein-based technology, one that has been around since the 1980s and is used in the Hepatitis B vaccine. Containing a protein of the coronavirus, it arms the body to recognise the virus and launch an immune response against it. It is unlike Covaxin, which contains the whole virus but in an inactivated form. And since this vaccine contains only a part of the virus, an adjuvant is added to make the immune response stronger.
Covovax, also a recombinant-based vaccine, developed by the US-based Novavax, will be produced by the Pune-based Serum Institute of India. To develop it, researchers isolated the part of the genetic sequence of the virus that produces the spike protein and introduced it in baculoviruses or pathogens that attack insects, instead of using yeast as Corbevax does. Like all vaccines, Covovax tricks the immune system into believing it is under attack from the real virus.
Besides the vaccines, Molnupiravir—an anti-viral that its makers say can help with moderate Covid—has also been approved and 13 companies are set to manufacture the drug. But the Indian Council of Medical Research says the drug is unsafe. To achieve complete vaccination by mid-2022, production will also be ramped up by getting manufacturers to use available unutilised production spaces like the Integrated Vaccine Complex at Chengalpattu in Tamil Nadu.
Meanwhile, US Army researchers are developing a new “super vaccine” that can tackle the virus in all its mutations, as well as SARS-CoV-1, which was first detected in 2003. Known as the Spike Ferritin Nanoparticle (SpFN) vaccine, its creators say the shot generates strong binding antibody responses against the receptor-binding domain and spike proteins of all variants of concern. The US Army’s strategy is to develop a ‘pan-coronavirus’ vaccine technology that could potentially offer safe, effective and durable protection against multiple coronavirus strains and species.
Equally critical is developing a robust public health surveillance system. Epidemiologists say every state must have genomic surveillance in place, with a comprehensive sampling strategy to track any change. This will require regular testing a fixed number of samples from each part of every state. Some experts warn that new Covid-19 variants will keep appearing until the entire world has been vaccinated against the virus. They argue that sharing vaccines is not just an act of altruism but also of pragmatism. World Health Organization data reveals that the global Covid-19 toll in 2021, as of December 29, was 5,411,759, which exceeded the combined toll from HIV/ AIDS, tuberculosis and malaria in 2020. Vaccination is the only way forward.
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