New Delhi: As an entire year seems to have been lost to coronavirus, all eyes are on 2021 to answer some big questions about the thing everyone is waiting for, a Covid-19 vaccine. When will one be available? How much will it cost? How long before there is enough for herd immunity to be achieved? Will one vaccine be more safe or efficacious than others?
There are over a 100 vaccine candidates in various stages of development across the world, with many different technologies at play. This explainer will take you through the most promising vaccine candidates currently under trial, the companies manufacturing them, and explain what stage of development they are in, and the plans devised for their phased delivery and distribution.
But reader discretion is advised. Experts say the arrival of a vaccine may not be the end of all our worries.
“The speed of development is a response to the pandemic that has unsettled health and economy across the world,” said Dr K. Srinath Reddy, president of the Public Health Foundation of India (PHFI).
“When we develop something with this speed and launch it into public use — two potential areas of concern are that the safety may be overlooked in search for efficacy, and the second concern is whether the duration of protection is correctly assessed,” he added.
“For that, we need post-marketing follow-up. Even in terms of efficacy, we cannot gauge the nature of cellular immunity that has an impact on the duration of protection. We are looking at antibody levels and prevention of severe infection. We are not able to look at the duration of cellular immunity. These need to be looked at in the post-licensing phase.”
- Serum Institute – Covishield
Originally developed by researchers at the Jenner Institute in Oxford University, Covishield is widely believed to be one of the global frontrunners in the race for a Covid vaccine.
It has been made from a virus (ChAdOx1) — a weakened version of a common cold virus (adenovirus) isolated from chimpanzees. It is being commercially manufactured by the Swedish-British firm AstraZeneca and the Pune-based Serum Institute of India (SII), a partner in the Oxford-AstraZeneca endeavour.
The SII and the Indian Council of Medical Research (ICMR) are currently conducting Phase 2/3 clinical trials — these phases involve a large number of participants, ranging from hundreds to thousands — of Covishield at 15 centres across the country. It completed the enrolment of 1,600 participants on 31 October.
An early analysis of data by the researchers involved has shown that the vaccine stopped an average of 70 per cent of participants from falling ill.
It is also being tested in large efficacy trials in the UK, Brazil, South Africa and the US. The SII has already manufactured 40 million doses of the vaccine, under the at-risk manufacturing and stockpiling licence from the government regulator Drugs Controller General of India (DCGI).
If the vaccine manages to get a nod from the UK regulator, it is possible that it can get expedited clearance in India by the end of the year or early next year, thanks to a provision in drug regulation norms that allows exceptions to be made for products that are approved by some countries like the UK, Germany etc.
While the efficacy data is still awaited, the first results of the safety analysis have reportedly shown it to be safe and immunogenic, that is, it generates an immune response in the body.
What’s more, trials have shown it to be better tolerated in older adults than younger ones. This is particularly good news because older people are among the most vulnerable to Covid-19.
The SII had originally announced that the vaccine would be priced at $3 or approximately Rs 225 per dose. However, it has now said it will cost about double that amount.
It is likely to be available by April 2021.
2. Moderna – mRNA-1273
mRNA-1273 was the first Covid vaccine that went into human trials — starting March this year — and was touted as the most promising one then.
It is based on a messenger RNA platform that carries the code for the SARS-CoV2 spike protein. This mechanism teaches the body to recognise the virus and mount an immune response when the actual invasion happens.
The first interim analysis of the vaccine’s efficacy — made public this month — reportedly showed that the vaccine had a 94.5 per cent efficacy. There were no immediate safety concerns, and side-effects included things like injection site pain, muscle pain, headache and fatigue.
This study, known as COVE, enrolled more than 30,000 participants in the US and is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the US government’s National Institutes of Health (NIH), and several other organisations.
The vaccine is expected to cost around $35 (approx. Rs 2,600) for a dose. It remains stable at 2°C to 8°C (36°F to 46°F), the temperature of a standard home or medical refrigerator, for 30 days. At -20°C, it can stay for up to four months, researchers say.
There is no clarity on when it may be available in India.
3. Pfizer – BNT162b2
At a time when the world was straining for good news about a vaccine, US pharma giant Pfizer and its German partner BioNTech created a flutter when they announced this month that their vaccine candidate BNT162b2 — also an mRNA vaccine — had shown an efficacy of 95 per cent in the final analysis of clinical-trial data.
Based on current projections, the company expects to produce up to 50 million vaccine doses in 2020 globally, and up to 1.3 billion in 2021.
However, there is no clarity on when this vaccine will reach India — the fact that it needs to be stored at a temperature of -80 to -90 degrees Celsius has stoked some jitters about transportation and storage.
4. Russia – Sputnik V
In August, Sputnik V, developed by the Russian government’s Gamaleya Center and the Russian Direct Investment Fund (Russia’s sovereign wealth fund), became the first Covid vaccine in the world to be registered.
After the first interim analysis, its makers said, the vaccine was found to be 92 per cent effective in preventing Covid. No unexpected adverse events were reported. Some of those vaccinated had short-term minor adverse events such as pain at the injection site and flu-like symptoms, including fever, weakness, fatigue, and headache.
The governments of India and Russia are collaborating on holding clinical trials in India at the earliest. Hyderabad-based Dr Reddy’s Laboratories has got approval to this end for a small trial.
The existing RDIF contracts with international partners enable the production of 500 million doses of the Sputnik V vaccine outside Russia annually.
There is no clarity yet on how much the vaccine will cost.
5. Bharat Biotech – Covaxin
Covaxin, India’s indigenous Covid-19 vaccine by Bharat Biotech, was developed in collaboration with the ICMR’s National Institute of Virology (NIV). The vaccine has now completed Phase I and II clinical trials and the company is all set to start Phase III.
While the vaccine will not be available before 2021, Bharat Biotech MD Dr Krishna Ella has been quoted as saying that it will cost “less than a water bottle”. There is a lot of excitement about the vaccine’s provenance and the company’s record of making affordable vaccines, but it is unlikely to be the first one to be available in India.
Haryana minister Anil Vij got the first trial dose of the vaccine Friday. Phase I of the Covaxin trial resulted in an adverse event in one of the trial participants but the company claims it was not vaccine-related. The patient is now reportedly fine.
6. Zydus Cadila – Zycov D
Developed along with India’s Department of Biotechnology, Zycov D is a DNA vaccine that is all set to begin Phase III trials. In the pre-clinical phase, the vaccine was found to elicit a strong immune response in multiple animal species like mice, rats, guinea pigs and rabbits.
No safety concerns were observed for the vaccine candidate in repeat dose toxicology studies involving both intramuscular and intradermal routes of administration. In rabbits, up to three times the intended human dose was found to be safe, well-tolerated and immunogenic.
If the results of the Phase III trials are in keeping with expectations, the vaccine is likely to be launched by March next year. As it is funded by the department of biotechnology, the vaccine is likely to be an affordable one.
Immunogenicity testing is in progress.
7. Gennova Biopharmaceuticals’ Covid vaccine
This is India’s very own mRNA vaccine, seed-funded by the Department of Biotechnology. The vaccine is likely to be in clinical trials soon and has some time to go before it becomes available.
8. Biological E – Ad26.COV2.S
Hyderabad-based Biological E. Limited has entered into an agreement with Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, for the manufacture of vaccine candidate Ad26.COV2.S.
This is based on an adenovirus vector, but what makes it unique is the fact that this is a single-dose vaccine, unlike the others mentioned above. The vaccine is currently in Phase 1/2a clinical trials (2a trials focus on dosage requirements, while 2b is about testing efficacy).
‘Technology matters very little’
Experts say the technology employed by different vaccines is unlikely to alter the outcome — that is, offering patients protection from the disease.
Dr Gagandeep Kang, professor in the Department of Gastrointestinal Sciences at the Christian Medical College Vellore, said the technology is important but only to a limited extent.
“Vaccines have the same goal. The idea is to protect people from disease, if possible, protect them from infection. The platform doesn’t matter but it determines how the vaccine works and fits into the system,” she said.
“An inactivated vaccine is not the same as a replicating vaccine. The latter — whether a replicating inactivated SARS-CoV2 vaccine or a viral vector that replicates — allows a single-dose vaccine. For others, you need more than one dose,” she added.
“If you want to guide the cellular immune response in a particular direction… that can be determined by the platform. The other aspect is that the platform decides our ability to store and distribute the vaccine.”
Among experts, there is cautious optimism about the results published so far. “These are news releases from different manufacturers. We have not yet seen the results in scientific journals and these are interim results. While we can feel hopeful about these spectacular results we should not be exuberant in our celebrations because these need to be withstanding scientific scrutiny and regulatory appraisal,” said Dr Reddy.
“However, it does give us hope that it is possible we will see greater degree of success than some of the others in the past.”
While many countries across the world are pre-buying vaccine stocks, India has taken a wait-and-watch approach. Even so, the government has devised a strategy on distribution that prioritises vaccine administration on doctors and health workers.
The key question as India begins to prepare for immunisation will be vaccine availability, its mode of administration, and storage requirements.
Earlier this month, AIIMS director Dr Randeep Guleria said Covid vaccination would stretch to 2022. Dr Kang agreed, saying an average citizen who is not among the priority groups can realistically hope to get the vaccine only after 2021.
“If we look at all the vaccine priority groups, healthcare and frontline workers, elderly people, those with comorbidities, constitute about 30 per cent of any country’s population. For India that is about 400 million people,” she said.
“So, if we do more than 800 million doses next year… I agree with Dr Guleria, we will be looking at 2022 but it is difficult to say till we have a licensed product.”
‘Vaccines are not the end’
Earlier this month, the World Health Organization said vaccines alone will not end the pandemic.
Dr Reddy echoed the view. “We don’t know how long the duration of protection will be and we don’t know if the second cycle (of infections) will start even among those immunised,” he said.
“The degree of vulnerability at the population level, we do not know. We also do not know about mutant strains. If there is inequity in distribution of the vaccine globally, some populations could get it earlier and others later. People immunised later could travel to these countries that received it first and, if immunity is of one-two years, the cycle can get restarted,” he added.
“Also, the vaccines do not prevent the virus from staying in the nose and people can still spread it. That is why public-health measures will need to continue to some degree till this is exorcised across the globe.”