Survival through inoculation

On the joyful afternoon on 31 December 2019, people were gearing up to welcome the New Year, with intense celebrations. But a handful of people sitting in the WHO’s office in the People’s Republic of China were anxious. The Wuhan Municipal Health Commission had declared that it had detected a cluster of cases of pneumonia of an unknown nature.

On 7 January 2020, the Chinese authorities finally isolated the causative organism, a novel coronavirus. It was later named the SARS-CoV-2 and the disease was called COVID-19.

Genetic sequencing of the virus was carried out and shared with the world on 12 January 2020. By 20 January 2020, the disease had spread to Thailand, Japan and the Republic of Korea. The WHO declared it a Public Health Emergency of International Concern on 30 January 2020 and a pandemic on 11 March 2020.

Due to its novel nature, the world lacked vaccines and chemotherapeutic interventions against SARS-CoV-2. The highly infectious virus had struck mankind with unprecedented force and created an unparalleled existential crisis.

Initially, countries responded with soft public health measures such as screening, quarantine and social distancing. When these measures could not stem the spread of the disease, sealing of outbreak hotspots, lockdowns and curfews were resorted to. This impeded economic activity and shattered livelihoods.

By 11 April 2022, the world had seen at least three waves of the disease, with the number of confirmed cases reported to the WHO mounting to 497,057,239 (including 6,179,104 deaths). India reported 4,30,36,928 cases, including 521,710 deaths.

ILLUSIVE SEARCH FOR ‘PATIENT ZERO’

The search for the first human infected by the virus, called ‘patient zero’ or the index case, began as soon as the new virus was reported. This was critical to establishing new zoonotic reservoirs and preventing re-infection. Early cases revealed an association with the Huanan Seafood Wholesale Market in Wuhan, China, and suggested a human-animal interface.

However, retrospective investigations concluded that the first patient of COVID-19 who reported to a hospital on 1 December 2019 had no links with the Huanan market. Subsequent genome analysis and studies suggested that the virus had jumped from animals to humans as early as September 2019.

Conclusive proof of how and when the contagion crossed over to humans is yet to be unravelled. In spite of innumerable controversial theories on the internet, finding patient zero for COVID-19 remains elusive.

DID THE MONSTER EMERGE NATURALLY?

China is a strong proponent of the theory of the natural origin of SARS-CoV-2. It posited that the contagion emerged simultaneously in different countries. Some viral genome experts are of the view that the virus is closely related to a coronavirus that came from a bat in a cave in China in 2014.

On 18 May 2020, the World Health Assembly resolved to identify the zoonotic source of the virus and the route of its introduction to the human population. But due to stiff resistance from China, the joint team could only visit the country in January 2021, and that too, under strict limitations.

The team’s report, published on 30 March 2021, brought out that SARS-CoV-2 jumping from bats to humans via an intermediary animal was the most probable reason for the spread of the disease. The virus escaping from a laboratory was the least probable of the four scenarios considered. However, the report categorically stated that the data examined was insufficient.

The inclusion of 17 Chinese scientists in the team, the lack of access to complete, original data and samples about the early stages of the outbreak, inability to find the intermediate host and China’s refusal to share the activity log of scientists at the Wuhan Lab also affected the credibility of the report. According to a section of experts, the conclusions lacked scientific justification and the lab leak hypothesis was given only a cursory look.

Countries including India demanded a comprehensive, independent, expert-led investigation to determine the origin of the pandemic.

DID THE VIRUS ESCAPE FROM A LAB?

As the pandemic ravaged nations, voices proffering scientific evidence in favour of a lab leak grew louder. The Huanan market, the initial epicentre of COVID-19, is just 25–30 kilometres from the Wuhan Institute of Virology (WIV). Scientists at the institute conduct research on coronaviruses, including on the SARS-CoV-2 family.

The inability to identify the intermediary host, lack of total access to the WIV, and adequate mutations in a bat virus to be infective to humans supplemented the lab-leak theory. The bat species believed to be the source of SARS-CoV-2 is found around 1,500 kilometres from Wuhan. Therefore, the contagion could not have appeared in Wuhan without infecting people en route.

In a paper, two Chinese researchers, Botao Xiao and Lei Xiao, also claimed that the killer coronavirus originated from the Wuhan lab. However, their conclusions were based on assumptions and lacked scientific evidence. Stating that the bats carrying the SARSCoV-2 were originally found in the Yunnan or Xhejiang provinces, which were about 900 km from Wuhan, they concluded that the possibility of bats reaching Wuhan was slim.

In May 2021, Republican members of the US House Permanent Select Committee on Intelligence (HPSCI) released a report titled Covid-19 and the Wuhan Institute of Virology. The report claimed that ‘significant circumstantial evidence’ exists for the viral leak from WIV.

According to a US intelligence report, many researchers working at the WIV had to be hospitalized in November 2019, with symptoms consistent with COVID-19. However, the Director of National Intelligence said that both the natural origin and a lab leak are plausible hypotheses for the first infection of a human being by SARS-CoV-2. British intelligence agencies have also agreed about the feasibility of emergence of the pandemic through a viral leak.

According to some reports, the virus found it difficult to adjust back to bats, which suggests that it was genetically engineered in a lab. A section of scientists believe that SARS-CoV-2 originated from ‘gain of function’ research. In such research, pathogens are genetically engineered to make them more infectious. Fingers were pointed at Shi Zhengli, a top Chinese virologist who is also known as the ‘Bat Woman of China’.

SEARCH FOR A SAFE AND EFFICACIOUS VACCINE

The commitment of huge resources on public health interventions was unable to vanquish the contagion. As the pandemic unfolded, the world increasingly turned to vaccines to save lives and take the global economy on a recovery path. Thus, an unprecedented global quest for COVID-19 vaccines began.

However, development of vaccines is a cost-intensive process, and often spills over a decade. Vaccine-manufacturing also requires highly regulated and expensive facilities. How would the world get a COVID-19 vaccine at such a breakneck speed?

ACCELERATED VACCINE DEVELOPMENT ENDEAVOURS IN THE PRE-COVID-19 ERA

Scientists and manufacturers have experimented with compressed vaccine development timelines during past outbreaks. In the case of the H1N1/Swine-Flu outbreak in 2009, vaccines were developed swiftly. This was made possible by existing, well-developed influenza vaccine technologies and licencing of vaccines under the rules.

In the case of the Ebola outbreak in West Africa in 2014, scientists used an existing technology developed for the HIV vaccine for a swift outcome. Phase 3 trials started within a year of the eruption of the pandemic. Although the vaccine was used on ‘compassionate’ grounds to control an epidemic in Congo in 2018, it could only be licensed in 2019.

Development of vaccines for the Zika, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) viruses also began at a rapid pace. But none of them went past the first stages of development and testing before the virus disappeared.

DEVELOPING A VACCINE IN A FEW MONTHS

In the case of COVID-19, the global humanitarian crisis created a state of force majeure. It challenged the orthodoxy in vaccine development and resulted in churning out of vaccines at a dizzying pace.

The colossal efforts of contagion led governments, scientists and manufacturers to find ways to chop not just months but years off the timeline, led to success. The discovery phase, the lead candidate optimization, the preclinical studies and starting of clinical trials happened within two months of the onset of the pandemic.

A rich bouquet of vaccines was ready in less than a year of declaration of the disease as a Public Health Emergency of International Concern. But how was this monumental feat achieved?

UNPRECEDENTED COLLABORATION

Intense global collaboration will be remembered in history as the reason for the COVID-19 vaccine development. Industry, academia, regulatory bodies, philanthropists and governments joined hands to develop multiple, safe and effective vaccines.

While the USA launched Operation Warp Speed, the Indian government came up with Mission COVID Suraksha. Many other governments and the European Commission have also funded vaccine candidates.

A global collaborative project, the Access to COVID-19 Tools Accelerator (ACT-A), was launched in April 2020 to fight COVID-19. It has four pillars: vaccines, therapeutics, diagnostics and the foundational Health System Connector.

The COVAX facility, the vaccine pillar of the ACT-A, was founded by the WHO, the GAVI Alliance, the CEPI Alliance and the Bill & Melinda Gates Foundation. It supports research, development and manufacturing of COVID-19 vaccine candidates, negotiates prices and facilitates equitable distribution of vaccines.

Going a step further, India sent a proposal to the WTO in October 2020 for a temporary waiver of the Trade-related Aspects of Intellectual Property Rights provisions.

Knowledge-sharing on a real-time basis was the hallmark of COVID-19 vaccine development efforts. The genome of the contagion was sequenced and published quickly, providing researchers with the genetic instructions for making the spike protein, a key ingredient for developing vaccines. Information sharing about related coronaviruses, SARS and MERS also helped in saving the critical development time.

MULTIPLE NEW TECHNOLOGY PLATFORMS

COVID-19 vaccine development will also be known for the use of novel platform technologies. Messenger RNA (mRNA) was one such platform. It does not require the production of loads of viruses. Scientists only need to know the genetic sequence of a virus to string together the right pieces of the code to synthesize viral antigens in a lab.

When injected, mRNA works as an instruction book for the protein-making machinery in human cells to produce a protein found on the surface of SARS-CoV-2. This spike protein triggers an immune response to the virus.

Earlier, identification of a suitable antigen would take years, but advancements in genomics and structural biology led to the quick mapping of the COVID-19 antigen. This led to the production of the first batch of clinical-grade vaccine material on 7 February 2020, barely four weeks after the publication of the genome sequence. The first dose was administered to a patient on 16 March 2020.

Another novel platform technology used was a viral vector, which was used earlier to develop Ebola vaccines. The RNA sequence of the antigen that triggers an immune response was added to a piece of the genome of a disabled virus to create a vaccine candidate.

(Excerpted with permission from Sajjan Singh Yadav’s India’s Vaccine Growth Story; published by Penguin)