Nearly eight months into the coronavirus pandemic, new infections in India have finally slowed down, according to official data. But as several countries in Europe again impose lockdowns and the United States records more daily cases than ever, it seems inevitable that India too will be hit by a second wave.

In the meantime, as we swing from needless hygiene theatre to pandemic fatigue, vaccines seem to be the most promising exit plan. But it is illusory to expect a vaccine to reinstate the pre-pandemic normalcy.

Best bets

More than are currently in trial. But our best bets are the handful in phase three trials that may get approval in the next few months – from Pfizer, Johnson and Johnson, Moderna, AstraZeneca/Oxford, Novavax, and CanSino.

Two of these are undergoing trials in India, according to the , which is leading the country’s pandemic response. First is Oxford and AstraZeneca’s , a billion doses of which are being made in partnership with the Serum Institute of India, half of those for domestic use. This is likely our best bet.

The Serum Institute will also manufacture a of Novavax’s candidate for low- and middle-income countries, including India.

Then, there’s the indigenous , developed by the ICMR and the National Institute of Virology, and manufactured by Bharat Biotech. Though this inactivated vaccine is built on a more reliable platform, it's still in early phase three trial and at least six months behind the frontrunners. , a DNA vaccine candidate from Zydus Cadila, is further behind.

Vaccines are to succeed in clinical trials than other therapeutics. Even then, an average vaccine takes to develop and has only a probability of entering the market. Only candidates that undergo clinical trials succeed, according to WHO. But this volatility is the nature of biopharmaceutical licensing.

Vaccine candidates from Pfizer, Moderna and Zydus Cadila are built on experimental mRNA and DNA platforms that have to make a commercial vaccine before. Similarly, a from the European regulator EMA aside, the adenovirus vector vaccine platform used by Oxford, Johnson and Johnson, Gamaleya, and CanSino hasn’t yet produced an FDA-approved vaccine. An adenovirus vector vaccine for HIV was abandoned in showed that it was not only ineffective, but even exacerbated HIV infection in some participants.

Vaccines built on more reliable platforms are months behind in development than the frontrunners and they would likely be once first approvals are granted. Novavax has spent over 30 years developing vaccines. Yet, the company, which was recently awarded $1.6 billion by the US government, does not have a single licensed vaccine in the market.

Given the trials of these frontrunner candidates have been extended, the optimistic timeline of late 2020 for a vaccine has been , and the rollout will likely be more staggered than what we currently assume.

Beyond the gravestone of hydroxychloroquine, this pandemic has seen pharma giants bulldoze their way through regulatory approval. Remdesivir, an antiviral made by Gilead, in spite of falling flat in multiple , was , and even secured a highly lucrative contract from .

Indian regulators, under the garb of “”, approved and despite unreliable data on their efficacy. This pattern of regulatory authorities bowing to political and corporate pressure makes it easier for a poor quality vaccine to fly under the radar.

For all this scepticism, vaccines absolutely do work. They have a remarkable , have helped save millions of lives, mostly children, and become indispensable to public health. In the past 10 years alone, vaccines have saved an estimated .

Measuring efficacy

For most vaccine candidates, data from phase one and two trials has been promising. They spur immune response and produce healthy amounts of neutralizing antibodies. But virus titer reduction or antibody production tells us little about the efficacy. By what amount the vaccine reduces Covid infection is the critical question. And phase three trials seek to answer that.

Let’s look at what a simplified average phase three trial looks like. We recruit 30,000 people. Half of them are immunised with our vaccine candidate and the rest are given a placebo. We wait for 150 events, each a predetermined endpoint such as an RT-PCR positive test at recurring intervals. We then look at the distribution of the events between vaccine and placebo to calculate its efficacy.

Measuring the events can tell us different things. Depending on what we’re measuring, we can see whether they decrease infection, , disease, infectiousness. All trials of the current frontrunners only measure reduction in the risk of mild infection, and tell us moderate or severe disease.

Preventing disease in the vaccinated person is direct protection. Preventing the person from transmitting the virus to others is . In a country such as India, where vaccinating the majority of the people would take months, indirect protection would be crucial to controlling case surges. Based on in apes, it’s unlikely that any of the frontrunners would prevent transmission.

Along with efficacy, phase three trials check for safety and rare adverse events that are only highlighted when there are thousands of participants. All the approvals that we will see granted in the coming months will be based on interim data and most phase three trials, involving , , candidates, won't end before late 2021.

, and have all set a bar of at least 50 percent efficacy in placebo-controlled trials for approval. This means if a moderately efficacious vaccine is licensed, it will end up becoming the benchmark for better candidates, making it to judge their true efficacy.

Like for repurposed drugs, WHO is running an international, randomised, for several vaccine candidates at once. The WHO Vaccine Solidarity trial aims to recruit across 34 countries. But its results will come only in , after most of the frontrunners would have been licensed and distributed.

The outcome of a trial also depends on the prevalence of the virus in the place where the vaccine is being tested. More the Covid cases, the faster the trial ends. But as Covid cases have begun to decline, so has the speed of some trials. Low attack rates because of immunity building, masking, and physical distancing will and maybe even halt some of the trials.

Another problem with the ongoing trials is that they are not diverse enough. For instance, older people who are at greater risk from Covid a strong immune response. on tolerability and dosage is therefore required for this population. Other disadvantaged people such as those who are , HIV positive, immunocompromised, or pregnant women are in the trials as well.

The longevity of protection against Covid is still unknown for the vaccines in development, and we will likely need every few years, or less.

Safety concerns

Reactogenicity is the body’s reaction to the administration of a vaccine, and usually involves some physical discomfort such as headache, fatigue, and fever. While these are manageable symptoms and signs, a vaccine with a poor tolerability profile might discourage some patients from taking it.

Of the frontrunners, the Oxford vaccine has the . In their phase one and two trials, Oxford scientists had to add where the participants receiving the vaccine were also given paracetamol every six hours for a day to manage the symptoms. Still, reactogenicity was significantly high as compared to the placebo, which was a vaccine but for another pathogen.

Source link