Mumbaikars expressed their gratitude to Oxford University-AstraZeneca through paintings at Lower Parel in July, after its vaccine showed positive signs during the early human trials. Pic/Getty Images

Closer home, the Pune-based Serum Institute of India (SII) received criticism for slapping a Rs 100 crore defamation suit against a COVID-19 vaccine volunteer, who allegedly suffered serious psychological and neurological side effects during the third phase of the Oxford University-AstraZeneca's Coronavirus vaccine trials (named Covishield by SII). He claimed a compensation of Rs 5 crore.

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As countries inch closer to authorising vaccines to fight the novel Coronavirus, the intent to participate in COVID-19 vaccination programmes is under question. Market research company Ipsos recently published an online survey of more than 18,000 adults from 15 countries conducted in partnership with the World Economic Forum between October 8 and 13. While 73 per cent said they would get a vaccine for COVID-19 if it were available, the numbers had seen a four per cent drop from three months earlier.

Namrata Ganneri, researcher and Feroze Mithiborwala, activist

Incidentally, India is one of the two countries to have not reported a change with 87 per cent individuals saying they'd take the vaccine if it were made available. The Chinese, on the other hand, have become the most sceptical of the lot, with a sharp 12 per cent dip (August to October) in intent to be vaccinated.

"This resistance to vaccination is not new," says Namrata Ganneri, who undertook a Commonwealth-funded research at the University of York (2018-2020), which focused on the early history of post-independent India's smallpox eradication programme. The smallpox vaccine—introduced by Edward Jenner in 1796—is one of the first successful vaccines to be developed in the world, also making it one of the oldest. The infectious disease came in two forms. Of these, variola major had a death rate of 20 per cent, while the weaker variola minor was at one per cent. Despite how deadly the disease was, people were suspicious of getting a vaccine. "Mass vaccination drives have always been resisted through history," says Mumbai-based Ganneri, discussing how in England when there was a powerful move to vaccinate, making it compulsory among the poorer classes of people, it was deeply resented. Something similar happened in India, too, though there is not enough documentation on this, she says. "The original form of vaccine, when it came here nearly two centuries ago, was transferred exclusively from arm to arm. So, people didn't want to take it, because many thought they'd lose caste. Later, just before the small pox eradication programme was officially launched in the 1960s in India, a series of pilot projects conducted in different districts of the states also saw resistance. For instance, an official in Delhi [who was part of the vaccination drive] had reported about one Ahimsak Party that had made it difficult for them to carry out the pilots. It had taken a lot of convincing." But, had it not been for the stringent vaccination programme adopted by India between the 1960s and '70s—developing its own freeze-dried vaccine—smallpox would have continued to haunt the country, she says. "Because of the kind of diverse population we have, the information overload [fact and myth], and the general scepticism surrounding vaccination, convincing people that this is good for them is going to be India's biggest challenge," Ganneri thinks.

Awaken India Movement members during a protest at Shivaji Park in November, to oppose the government's mandatory mask policy and its vaccination agenda. Pic/Ashish Raje

Noted activist Feroze Mithiborwala is not one to discount science, but he believes that the COVID-19 pandemic is a result of a lab-generated virus, created for the benefit of a handful of pharma companies. Mithiborwala is a member of the Awaken India Movement that led protests at Marine Drive and Dadar in October and November respectively, to oppose the government's mandatory mask policy and its vaccination agenda. On Friday, he joined a panel discussion at Marathi Patrakar Sangh in Azad Maidan, to discuss "why a vaccine was not required for COVID-19".

"It [the virus] is a bio weapon unleashed upon humanity," he claims. The virus, in itself, is not virulent. The infection curve is already tapering. A majority of slum residents have developed antibodies (against the virus) due to herd immunity. So, if a large population is becoming immune, why do we need a vaccine to begin with?" he asks. He says that news reports over the last few days have been worrying, referring to the Covishield vaccine participant, a 40-year-old Chennai-based man, who had allegedly suffered an adverse reaction, and was admitted to the ICU, where he was battling neurological complications. He also reportedly suffered memory loss for nine days. The legal notice by the man's family claimed that he had been "assured" that the vaccine was "safe". The claim is being investigated by the Drugs Controller General of India and the institutional ethics committee at the trial site. "Instead of assuring the family members, Serum Institute went ahead and slapped a R100 crore defamation suit against them," says Mithiborwala, adding that the lack of legal liability and accountability of pharma companies was disturbing.

Prime Minister Narendra Modi briefed by Cyrus Poonawalla at Serum Institute of India in Pune, during his three-city visit to review COVID-19 vaccine development. Pic/PTI

The one positive news, if at all, he says, is that the Indian Council of Medical Research and health secretary Rajesh Bhushan said that this vaccine may not be needed for all. "But it's likely that when available, the vaccine used for government officials and health workers would be different from the one given to the masses," claims Mithiborwala, pointing to a 2009 investigation by German weekly news magazine, Der Spiegel, on the swine flu vaccination programme. The report indicated that ministers and subordinate authorities were to receive a vaccine without controversial additives, unlike that for the general population.

Irrespective, an informed choice is needed before taking any vaccine, says Bhubaneswar-based Jagannath Chatterjee, who speaks from experience. Chatterjee suffered an adverse reaction to a vaccine back in 1979, when he was 17. "My doctor had recommended it, and I took it, without asking what vaccine it was. Later, I was told that I'd been given the MMR vaccine [against measles, mumps, and rubella]. It was highly unusual to give a teenager that vaccine [the first dose is generally given to children between nine and 15 months old]. Within weeks of taking it, I developed symptoms. I was diagnosed with multiple sclerosis, a neuromuscular disease. Memory loss and irritability had also become common, and I was later found to have bipolar disorder. The doctor refused to acknowledge that these symptoms were due to the vaccine."

Dr Cyrus Poonawalla, chairman of Serum Institute of India, and son Adar, CEO, drew flak for slapping a Rs 100 crore defamation suit against a COVID-19 vaccine volunteer, who demanded Rs 5 crore compensation, after he claimed that he suffered neurological complications during trials. Pic/Ashish Rane

Since then, Chatterjee has been writing and researching about vaccines. He is hoping his efforts will make people more aware of the risks. Ever since the pandemic broke out, Chatterjee has been preparing meticulous notes on the novel Coronavirus and the vaccination programmes across the globe, updating it on a daily basis. "The concerns are many, but the authorities have a single worry: How to rush the vaccine through before the epidemic vanishes?" he feels.

According to The Wellcome Trust, a research-charity based in London, the average time to develop and make a vaccine publicly available, is usually 10 years. The break-neck speed at which vaccines are being developed for COVID-19 is unprecedented and phenomenal, even in the field of science.

A family member pays respects to a relative who died of the virus at Nigambodh Ghat, Delhi. Dr Anita Mathew, infectious disease specialist, Fortis Hospital, Mulund, says. "If this pandemic continues, we stand to lose several million lives in the next two years. Vaccination will make the numbers negligible." Pic/Getty Images

The phase one and two trials of the mRNA vaccines developed by Moderna and Pfizer, began in March and May respectively. Oxford-AstraZeneca's AZD1222, which uses a replication-deficient chimpanzee viral vector, based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein, began its trials in April. While Moderna and Pfizer's Phase 3 trials concluded in October, AZD1222 suffered a bump when it had to briefly halt the final trials in September, "after an adverse event" in the UK.

According to Chatterjee, "vaccine safety can never be determined in trials". "This is because vaccines are not tested against any genuine placebo, but against another vaccine, group of vaccines, the same vaccine minus the antigen [substance that causes your immune system to produce antibodies against it], or the highly reactive adjuvants [ingredient used in some vaccines that helps create a stronger immune response] used in vaccines. This makes them 'as reactive as the placebo' and therefore, deemed safe," he argues.

Pururaj Bhar, Jagannath Chatterjee and Yohan Tengra

In an article for The Conversation, Jeremy Howick, director of the Oxford Empathy Programme, University of Oxford had also pointed out that "some researchers conducting clinical trials on the COVID-19 vaccine had not revealed to the public what the placebo contains, but they should". In some COVID-19 vaccine trials, participants in the control group—the group receiving a placebo—are injected with a saline solution. In other trials, they receive an actual treatment, like a meningitis or septicaemia vaccine. "The main problem with including something active in the placebo, such as another vaccine, is that it can confuse researchers when they measure side effects," Howick had written, spelling out the concerns raised by Chatterjee.

Chatterjee adds that the trial period too, is small to detect long-term adverse effects that vaccines are famous for. "Everything depends on post-marketing surveillance. But, nobody really looks out for adverse effects and therefore, reporting is very tardy," he feels.

Dr Anita Mathew and Dr Khusrav Bajan

Dr Maya Valecha, a Gujarat-based gynaecologist, feels that the current number of positive cases, which is driving the urgency for a vaccine, has been inflated. "The RT-PCR tests are not foolproof, [they are said to pick up all kinds of virus]. That means it is not completely reliable. How then, are we using it to determine COVID-19 positive cases?"

Yohan Tengra, a consultant with a functional nutrition clinic, who spearheaded the anti-mask protest in Marine Drive, says it's worrying that almost all leading researchers have skipped the animal trials for COVID-19 vaccine. "It's not that efforts have not been made to develop Coronavirus vaccines [MERS and SARS] in the past. Those vaccines were successful, too." But it backfired, with tested animals reportedly dying, he says. "That's the reason why they halted the previous vaccination programmes." In their petition to the European Medicine Agency, Dr Yeadon and Dr Wodarg, had raised this issue. They said that the formation of so-called "non-neutralising antibodies" could lead to an exaggerated immune reaction, especially when the test person was confronted with the real, "wild" virus after vaccination. "This so-called antibody-dependent amplification, ADE, has long been known from experiments with Corona vaccines in cats, for example. In the course of these studies, all cats that initially tolerated the vaccination well, died after catching the wild virus," the duo said.

Tengra also fears that when the vaccine is rolled out, it will not just pose health risks, but also risk to our "privacy and bodily autonomy". "I don't think the government is going to make it [vaccination] mandatory, but they will require people to have vaccine certificates and then those certificates will be needed to trade, travel, and live a normal life."

In 2019, the World Health Organisation named vaccine hesitancy—a reluctance or refusal to vaccinate—as one of the 10 biggest health threats facing the world. Vaccination, the WHO reported, is one of the most cost-effective ways of avoiding disease and currently "prevents 2-3 million deaths a year". "A further 1.5 million could be avoided if global coverage of vaccinations improved," the WHO said, while highlighting that cases of measles had seen a 30 per cent increase all over the world, with vaccine hesitancy likely as one of the many "complex" reasons for the same.

While Dr Anita Mathew, infectious disease specialist, Fortis Hospital, Mulund, admits that this is the first time in history that a vaccine has been fast-tracked, due to which safety data—otherwise available only after two years—isn't going to be immediately accessible, vaccines, she argues, are generally far safer than anything else used to treat infection. "For example, the side effects of over-the-counter medicines can be far more severe than getting a vaccine shot," she says. "If this pandemic continues, we stand to lose several million lives in the next two years. Vaccinations will make the numbers negligible," she says.

Interestingly, even some people who have lost loved ones to the virus are questioning the vaccine push. Mumbai Central resident Sayed Amin, who lost his brother Sayed Maqbool, 63, in a suspected case of COVID-19 in May this year, says despite the loss, he is unlikely to be in a hurry to get vaccinated. "My brother had severe kidney-related complications from the beginning, due to which he'd fall ill regularly. In May, he developed pneumonia. These were the early days of Coronavirus, and doctors were still figuring out, how best to treat patients. There was an overload of information on social media during that time. I feel the same is happening now with the vaccine. As someone, who has spent so many years negotiating hospital rooms, because of my brother, I have reasons to worry. I won't risk taking a vaccine, unless it's safe."

But, that's not the popular sentiment. Author and writing coach Sudha Menon, who lost a family friend to COVID-19 says, "He was a doctor, and my husband's close friend. They were classmates since kindergarten. The family is shattered and so is everybody who knew him. He probably contracted the virus from the patients he was treating. Tragic. If a vaccine will protect us from this, why not?"

Dr Khusrav Bajan, critical care consultant and head, emergency medicine, at PD Hinduja National Hospital, says that for any vaccine to get a green signal, it has to have at least 90 per cent efficacy [see box], with an excellent safety profile. "In my view, the Oxford vaccine is reasonably safer, because it is a non-replicating one. Enough trials have been done over a large group [of people]. The advantage of this vaccine is that it can be stored in a regular refrigerator. The other mRNA vaccines will take a while to reach us, since countries like the US and UK will buy off a decent stock. We also have our own vaccine, Covaxin by Bharat Biotech, currently undergoing trials," says Dr Bajan.

Why would anyone want a vaccine? "Because it will give you natural immunity, without falling sick, and also ensure that you don't give the infection to someone else in the family or outside, who is at a higher risk," says Dr Bajan. "There are many myths [related to the vaccine] that are floating. First of which is that if one takes the vaccine, they will be injecting the virus into their bodies, which is wrong. And the other is about side effects—the truth is that any vaccine will give influenza-like side effects in the beginning, [mild sore throat or fever], but that is part of the antigen process," says Dr Bajan, adding, "What we don't know yet is the long-term effects of the vaccine, and whether it will provide life-time immunity against the disease. We are yet to get clarity on that."

While the Centre hasn't released a definitive vaccination programme, both Dr Bajan and Dr Mathew feel that it's not going to be made mandatory. "The vaccines might roll out by late December or January. In a perfect scenario, we should have had enough vaccines to vaccinate everyone in the country. But, this is not an ideal world. So, healthcare workers are going to be the first to receive it, followed by those in the essential services, and then the high-risk elderly individuals with comorbidities. Authorities will need to select very carefully," says Dr Bajan, who is also a key member of the state government-appointed COVID-19 task force. Dr Mathew adds, "Enforcing a vaccine [on someone] is never a great move. If that happens, it will be resisted strongly. Honestly, we don't need to vaccinate everyone. Those most at risk have to be vaccinated, and that will ensure that the rest will be safe."

For herd immunity to kick in, at least 70 to 75 per cent of the population needs to have developed antibodies. Dr Bajan, however, says that this should not become an excuse to refuse a vaccine. "That's a cowardly way of going about things. We can't wait for that [herd immunity]… it's like sitting back and doing nothing. It's going to cost us many lives."

Pururaj Bhar, a partner in a leading Mumbai-based law firm, says he doesn't mind waiting for a few months before getting a vaccine shot. "I'd prefer a vaccine that has been administered extensively over a reasonable period of time without any major adverse event, in a developed country with a strong regulatory system," says Bhar. "It's likely that at least initially, we'd be dependent on the government, and won't have a choice over which vaccine to get. But, capitalism finds its way. India has a huge middle-class and upper-class population, which means that we have a good market that can pay for itself. At some point, pharma companies will monetise their vaccines, and I am sure, whoever is willing to pay, will get what they want." Varun Shreedhar Chitnis, editor with a metadata firm, said that because he is diabetic, he doesn't want to rush into getting a jab.

According to Dr Bajan, the vaccine is likely to be accessible to masses only in the coming six months or so. "That depends on how many [vaccines], we have procured. There are five key players [vaccines] right now. At different months, I think we will have different vaccines made available. They will eventually cater to all." He adds, "India is the largest producer of [all kinds of] vaccines in the world, and already has the world's largest Universal Immunisation Programme (UIP) in place. I think, we will have the best practices in place, even when it comes to this drive."

Until then, Dr Bajan says wearing of masks should be made mandatory. "It's our best shield against the virus, at least for now. Even if you do contract the virus, reports have indicated that using the mask helps bring down the rate of the viral infection. A vaccine is never going to replace the mask."

2-3M
No. of deaths prevented by vaccinations worldwide according to WHO, which in 2019 named vaccine hesitancy one of the 10 biggest health threats facing the world

Science behind vaccine efficacy

In a Twitter thread, Natalie E Dean (@nataliexdean), assistant professor of Biostatistics at University of Florida, gave a primer on vaccine efficacy:

. Vaccine efficacy (VE) measures the relative reduction in infection/disease for the vaccinated arm versus the unvaccinated arm. A perfect vaccine would eliminate risk entirely, so VE = 1 or 100%. This can be calculated from the risk ratio, incidence rate ratio, or hazard ratio (sic).

. Vaccine efficacy of 50% roughly means you have a 50% reduced risk of becoming sick compared to an otherwise similar unvaccinated person.

. Though we talk about vaccine efficacy as a single number, there are actually several different types of vaccine efficacy, such as: efficacy to prevent infection (sterilising immunity); efficacy to prevent disease; efficacy to prevent severe disease, etc.

. Most Phase 3 trials are measuring efficacy to prevent disease as the primary analysis, with efficacy against infection and against severe disease as secondary analyses. Preventing infection entirely is the hardest to achieve. And of course, a vaccine that prevents infection will also prevent disease and severe disease. But we can have vaccinated people who are still infected, but their disease severity is lessened.

. A vaccine that prevents infection entirely provides indirect protection to others. But it is possible to have a vaccine that prevents disease, but individuals can still be infectious.

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Namrata Ganneri, researcher and Feroze Mithiborwala, activist