November 2020. It's been almost a year of the global pandemic. Intermittent lockdowns have become the new normal, organisations have comfortably switched to WFH mode even as masks and sanitisers become an inseparable part of life. The virus has infected an estimated 55.6 million people, killing 1.3 million worldwide.

As Covid-19 continues to spread, the race for developing a vaccine continues against the clock. Some of these have reached the trial stage and a couple of them have even reported high success rates.

A Covid vaccine will be one of the greatest inventions in the history of mankind, but its global effect also makes understanding the science of vaccination equally important.

Excerpts from 'The Coronavirus: What You Need to Know About the Global Pandemic' have been used with permission from the author to explain the pandemic and related science. We take you centuries back in time to give an insight into the invention of vaccines for one of the most frightful diseases of all times.

Edward Jenner & the History of Smallpox

Far in the past, smallpox inflicted terrible suffering on humanity. Hundreds of millions died of smallpox, those who survived were quite literally scarred for life. An English physician, Dr Edward Jenner, observed that milkmaids rarely suffered from smallpox. He hypothesised that milkmaids were protected against smallpox by an occupation infection they acquired called cowpox. Dr Jenner believed that pus from cowpox blisters on milkmaids might help protect others against smallpox.

"On 14 May 1796, a historic day in medicine, Jenner injected an eight-year-old schoolboy, James Phipps, with pus scraped from a milkmaid's cowpox blister. Later Dr Jenner inoculated James with smallpox scrapings several times but no disease followed. Jenner's experiment was a resounding success!" reads an excerpt from the book.

Soon after the vaccine was invented, the British started to ship the vaccine to India, the 'Jewel in the Crown' for its empire. The vaccine was transported arm to arm using live vaccine carriers; two children would be vaccinated at a time. When the blister formed, the pus would be used to vaccinate another two children. Eventually, the vaccine reached the Indian distribution hub in Bombay and by 1807, it is estimated that close to a million doses had been administered.

"On 9 December 1979, 183 years after Jenner's pioneering work, smallpox was confirmed to have been eradicated and in May 1980 the WHO issued its official declaration that 'the world and all its peoples have won freedom from smallpox'," states an excerpt.

The Jenner's Covid Connection

In 2020, The Jenner Institute, named after Dr Edward Jenner, developed a critical component of the Oxford AstraZeneca Covid-19 vaccine. Like the smallpox vaccine, the United Kingdom has once again provided a potentially life-saving vaccine to India, which the Serum Institute of India will manufacture for the whole world. There are over a hundred vaccines for Covid-19. Let's take a quick look at the different Covid-19 vaccines that might help end the pandemic.

Infographics: India Today DIU

When the coronavirus infects a human host, human white blood cells (WBCs) detect proteins on the coronavirus.

These proteins are called antigens and the human immune system mounts an immune repose against them. Like an infection, a vaccine produces immunity. The virus's key antigens are incorporated into a vaccine, and when administered, the immune system produces an immune response to these antigens.

The coronavirus's Spike protein, quite literally its key, helps it open a lock on a human cell and infect it. Covid-19 vaccines aim to train the human immune system to mount an immune response against the coronavirus's key S protein.

"There are four kinds of vaccines in development for Covid-19. Inactivated or attenuated coronavirus vaccines use a form of the virus that can't cause severe infection but has antigens to stimulate the immune system. Protein-based or subunit vaccines contain the proteins based antigens that will train the immune system to attack the coronavirus.

Infographics: India Today DIU

Viral vector vaccines use a harmless virus that is engineered to carry coronavirus genes or antigens. Genetic vaccines contain DNA or RNA that instructs host cells to make coronavirus proteins that then act as antigens and stimulate the immune system," reads another excerpt from the book.

Bharat Biotech has developed an inactivated coronavirus vaccine in partnership with the Indian Council of Medical Research and the National Institute of Virology. The vaccine is in the final phase of trials and if results are favourable, it may be available by early 2021.

Novavax, GSK, Sanofi and many other companies are developing protein-based coronavirus vaccines. The Novovax vaccine is in the final phase of clinical trials and results will be available early in 2021. Over a billion doses may be manufactured by the Serum Institute of India. Inactivated virus and protein-based vaccine platforms are time tested and several of them offer promise based on early data.

Infographics: India Today DIU

The most exciting and promising vaccines are viral vector and genetic vaccines. The vaccines by Oxford University AstraZeneca, Johnson and Johnson and Russia's Sputnik V are all viral vector vaccines. The Oxford AstraZeneca vaccine is in the final stages of clinical trials and interim results are expected very soon. The Serum Institute of India plans to manufacture billions of doses of the vaccine.

Genetic vaccines consist of DNA or RNA that contains the genetic code to make coronavirus antigens. Mass manufacturing this code is less time-consuming than mass manufacturing proteins, and these vaccines cleverly outsource protein manufacturing to cellular factories inside human cells. The Moderna and Pfizer/BioNTech vaccines are mRNA based while the Zydus vaccine is DNA based.

Pfizer and Moderna vaccine trials provided the world with much needed good news with interim results, indicating 95 per cent and 94.5 per cent efficacy respectively. Additionally, the Pfizer vaccine is 94 per cent effective in the elderly. Several other vaccines, like Pfizer and Moderna, target the coronavirus S protein.

The Oxford AstraZeneca, Novovax and Bharat Biotech vaccines are being manufactured in India, and it is hoped they may be as effective. There are DNA and mRNA vaccines in development in India and it is still possible that Moderna may license the manufacture of its vaccine to an Indian company.

Safety is the First Challenge

Early data on all vaccines indicated they are safe, but a patient who received the Oxford AstraZeneca vaccine had a severe side effect that causes paralysis called transverse myelitis. While long-term safety data is still awaited, coronavirus vaccines are undergoing rigorous studies to ensure they are safe.

"While there are many promising vaccine candidates, proving safety and efficacy is only one of the challenges. Once a vaccine candidate proves to be safe and effective, manufacturing and distributing billions of doses will be a monumental challenge. Billions of doses of vaccine need as many glass vials and if they are to retain potency, extensive cold chains need to be developed," an excerpt states.

Infographics: India Today DIU

Fortunately, the Bharat Biotech, Novovax, Oxford AstraZeneca and Johnson and Johnson vaccines can be transported and stored at 2 to 8° Celsius. Genetic vaccines usually require very cold temperatures for storage. The Pfizer vaccine requires temperatures as low as -70° Celcius, but Moderna has modified its vaccine so that it can be stored at 2 to 8° C for up to 30 days.

The Doses & Distribution

One of the difficulties we will face with most Covid-19 vaccines is that they require two injectable doses to be administered a few weeks apart. Early data indicates that the Johnson and Johnson vaccine is effective in a single injectable dose and this offers a unique advantage.

India will need billions of doses of Covid-19 vaccines. Fortunately, India is likely to have billions of combined doses of the Oxford AstraZeneca, Novovax, Bharat Biotech, Zydus and Sputnik V vaccines, among others.

However, India will face enormous logistic changes in distributing and administering them. Lakhs of health workers will be needed to persuade Indians to get vaccinated and then to vaccinate them. Manufacturing a safe and effective vaccine in a previously impossible timeline is just the first challenge. The major problem is in ensuring its distribution to the vast majority of the population.

Public health authorities will have to earn the public's buy into the vaccination programme. We will need to ensure the equitable distribution of the vaccine. India's experience in mass administering vaccines with the Pulse Polio programme and Universal Immunisation programme will prove to be useful in mass vaccinating hundreds of millions of Indians in an impossible timeline.

Infographics: India Today DIU

India's polio eradication efforts have given us a solid foundation for a Covid-19 mass vaccination programme. In fact, the polio programme was designed to be repurposed after the eradication of polio. The Pulse Polio programme involved setting up vaccination booths all over the country, organising human resources needed through employees and volunteers, immunising millions of children on national immunisation days, identifying the children who missed immunisations and even surveillance of vaccine efficacy.

Our polio eradication efforts also involved developing a robust cold chain with walk-in cold rooms, freezer rooms, deep freezers, ice-lined refrigerators and vaccine vial monitors that indicated if the cold chain failed at any point.

Around two centuries ago, the smallpox vaccine made its way from England to Mumbai by ship and live carried from arm to arm. In 2020, scientists all over the world, including in India, have delivered several promising vaccines in an impossible timeline.

The Covid-19 pandemic is still raging and another pandemic could be a reality in near future. The Covid-19 mass vaccination programme, if successful, may be one of our public health system's greatest moments.

(Dr Swapneil Parikh is author of The Coronavirus: What You Need to Know About the Global Pandemic)



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