COVER STORY . Is the race for a Covid-19 vaccine going a bit too fast?

* Countries and companies are throwing their might behind efforts to bring out therapies and vaccines to tackle the novel coronavirus

* Vaccine research has been collapsed into months, while drug-makers have committed to producing vaccine doses “at risk”

* The news of the Russian vaccine kicked up a furore in the scientific world

Two little words — known unknowns — have been haunting the world. The fear was underlined by Andrew Witty during his last visit to India as the chief executive of British medicines, vaccines and healthcare-products maker GlaxoSmithKine.

“We are getting worse (in terms of response), we are not getting better,” Witty told a select group of mediapersons in Mumbai in November 2016, referring to the world’s ill-prepared responses to health challenges such as Ebola, swine flu and bird flu.

He stressed the need for a global bio-defence mechanism with an armoury of vaccines for the next “known unknown”. In other words, a research network that would work during peacetime to help the world be better prepared for war.

Almost four years later, countries grapple with a virus that has put healthcare systems and hospitals under immense pressure and crippled economies. And the need for battling the known unknowns has never been this urgent.

But in that gloom, if there is a silver lining, it is in how countries and companies are throwing their might behind efforts to bring out therapies and vaccines to tackle the novel coronavirus. No mean task this, given that the virus is “brutal” in its simplicity and cruelty, as Dr Michael Ryan, the executive director of the World Health Organization’s (WHO) Health Emergencies Programme, recently put it.

As of this week, the virus had taken over 7,71,635 lives globally. The US, Brazil and India top the chart of Covid-19 confirmed cases. Countries such as New Zealand, which had successfully brought down the number of new cases to zero, are now dealing with the renewed rise of the virus.

But as the world learns a little more about the virus every day, the weaponry against the virus is also bulking up.

Coming together

A host of repurposed medicines (or existing drugs being evaluated in a new role against the virus) is being prescribed for “emergency use” and 167 vaccine candidates to deal with the virus are in the pipeline. According to the WHO, 29 of these are under clinical studies; a handful in advanced trials in humans.

It is an effort like never before, with the entire process of trials being fast-tracked for the production of an effective vaccine, if indeed there is one, in the fastest possible timeline. Many believe that a vaccine may be available in early 2021.

Vaccine research has been collapsed into months, while drug-makers have committed to producing vaccine doses “at risk”, even as scientists complete late-phase trials to test the vaccine for its safety and efficacy. And if that is not enough, countries are putting big money on companies to buy vaccines from them, the moment there is an approved product. This, in fact, has given rise to fears of “vaccine nationalism”, where richer countries are able to buy medicines, vaccines, ventilators and other such necessary items for their people, while low- and middle-income countries (LMIC) get left behind.

WHO has been seeking to facilitate equitable access to vaccines with its Covid-19 Vaccine Global Access (Covax) facility, a mechanism designed to guarantee prompt and fair access to Covid-19 vaccines worldwide. WHO’s chief scientist Soumya Swaminathan has said that Covax will need 18 billion dollars for 2 billion doses of a vaccine by the end 2021.

But all timeline projections for a workable vaccine got torpedoed last week, as Russia toldthe world it had a Covid-19 vaccine — “Sputnik V”. And in no less dramatic a fashion, Russian President Vladamir Putin said it had been administered to one of his daughters.

The news of the Russian vaccine kicked up a furore in the scientific world, for little data on it is available in the public domain as peer-reviewed publications. Naturally, concerns are being raised on its safety and efficacy.

Meanwhile, a few other vaccine candidates continue with advanced stages of human trials (Phase 3) where the vaccine candidate is tested for safety and efficacy on thousands of people. Among them are vaccine candidates from Moderna Inc (US), Oxford University-AstraZeneca combine (UK) and CanSino and Sinovac (China).

Big pharma players in the fray include Pfizer-BioNtec, the Sanofi-GlaxoSmithKline combine and Johnson and Johnson (J&J). Among the Indian contenders are Bharat Biotech, Zydus Cadila, Gennova Biopharmaceuticals, Biological E and Panacea Biotec, which are developing vaccines, and the Serum Institute of India (SII), which is in an alliance with the Oxford University-AstraZeneca combine and Novavax to produce their vaccines.

More recently, Biological E, another Indian company, entered into a production alliance with J&J in India.

“World’s fastest vaccine”

A vaccine, health experts believe, is the only way to effectively combat the virus.

“We’ve seen very clearly now... that only a small proportion of the population have acquired any kind of immunity to this virus,” Swaminathan said at an online technical update in June. “So, the only way to prevent further spread and transmission and to break that cycle would be to have an effective and safe vaccine that’s available to people all over the world.”

Covax aims at accelerating the research and development and manufacturing of vaccines, she said. The shortest time taken to develop a vaccine so far has been five years — and that was for the Ebola vaccine. A Zika vaccine was developed in about two years but it could not be tested more widely. “In general it takes eight to 10 years for a vaccine [to be developed] — from when the research begins to when it gets into people.”

Covid-19 is likely to see a vaccine produced in the shortest period of time so far. “We want to shorten that timeline to as short as possible: 12, a maximum of 18 months,” she said. “That would be unprecedented and can only happen through a global collaboration between scientists, academics, small companies, larger companies, the big pharma industry as well as member states, philanthropies, private and public sector, civil society to make sure that we put in place everything that’s needed to be able to test as many vaccine candidates as possible.”

If a vaccine was produced in 12-18 months, it would be “without precedent, the world’s fastest development of a vaccine”, said Witty, now director-general special envoy for ACT-Accelerator, another global initiative for equitable access to treatments and vaccines, at the June online event.

Global concerns

Public health activists and leaders from across the world are watching these efforts with concern, as rich and powerful countries make alliances with companies to source the Covid-19 vaccines. To give just a snapshot of the alliances across geographies, the US has agreed to fork out $2 billion to buy Covid-19 vaccine doses from Sanofi-GSK. The UK has committed to picking up 30 million doses from Pfizer-BioNtech. Italy, Germany, the Netherlands and Australia have alliances with AstraZeneca for the Oxford University vaccine. About 20 countries have reportedly lined up for the Russian vaccine.

The WHO has been urged right from the start to ensure there is equitable access to medicines, technology and vaccines brought out to tackle Covid-19. Apart from the fact that the world is in the thick of a pandemic, public health voices have called for these products to be rolled out free in the interest of public good. High prices and patent protection, they point out, will keep these critical medical products out of mass reach.

Vaccine prices per dose are still evolving. The SII has said that its vaccines will not cost more than 3 dollars (₹250 or so) in LMICs. It’s early days for the Indian vaccine, but the expectation is it will be given free by the government. But if two doses of the vaccines are needed for warding off Covid-19 — as is being surmised — it will be an expensive proposition even for the government, said Dr Arun Bhatt, a regulatory expert in clinical research, indicating that funding agencies may need to step in to support the scale of vaccination in India.

Prices of some of the international vaccine candidates are reportedly pegged at $32-37 per dose for Moderna’s vaccine, $19.50 per dose for Pfizer’s and about $10 per dose for J&J’s candidate.

Concerns are being raised on the prioritisation of the vaccine. Who gets the first vaccine and how will it be rolled out? Swaminathan says the WHO is developing a “fair allocation framework”, in consultation with member states and other partners, including civil society, for equitable allocation and access.

“It is in everybody’s interest to protect populations across all countries because economic recovery cannot take place if some parts of the world are having a raging epidemic while others are relatively protected,” she pointed out.

Not too long ago, public personalities including Nobel Laureates Muhammad Yunus, Malala Yousafzai and Kailash Satyarthi, artistes such as Shabana Azmi and businessmen Narayana Murthy and Ratan Tata made a representation to the WHO. They called for a world action plan for a “people’s vaccine” that would belong to everyone.

The world is still waiting.

Ready, steady, go

 

Vaccine candidates in India are hurtling towards the finishing line

Indian pharmaceutical companies are competing with one another, and with vaccine research groups in academic institutions, to develop a potential vaccine against Covid-19. In May this year, Prime Minister Narendra Modi said there were nearly 30 vaccine initiatives in the country.

So far, three vaccines candidates — two home-grown ones and one developed outside India — are undergoing clinical trials in India. All three have completed Phase 1 clinical trials. For any vaccine or therapeutic measure to succeed over the long term, it has to be safe, effective and cost-effective. Preclinical and Phase 1 studies look at safety, Phases 2-3 look at efficacy, while health economists and policymakers assess cost-effectiveness against their local threshold.

The vaccine developed by an Oxford University team but being produced in India by the Serum Institute of India, Pune, has just entered Phase 3 trials. The vaccines being developed by the Hyderabad-based Bharat Biotech India with the National Institute of Virology and the Gujarat-based pharma firm Zydus Cadila are now looking at Phase 2 trials. A vaccine will be allowed for human use only after the successful completion of Phase 3 trials.

While it would still be difficult to say which of the three (or any other being developed by others) will be the first available vaccine, the one manufactured by the Serum Institute — the world’s number one vaccine maker — has an edge over the others.

An update on the three front runners:

Covaxin: The Covid-19 candidate vaccine, being developed by Bharat Biotech and the National Institute of Virology, Pune, uses inactivated virus particles for eliciting an immune response. It has just completed Phase 1 clinical trials involving 375 volunteers conducted at 12 sites, including the All India Institute of Medical Sciences in New Delhi.

ZyCoV-D: Developed by Zydus Cadila, this proposed vaccine is being designed to introduce DNA that codes for a viral protein into human cells. Once in the human cells, the protein will prompt the cells in the body to raise an immune response against the SARS-CoV2 virus, which causes the Covid-19 infection. The recently concluded Phase 1 trial shows that the vaccine was well tolerated by those who received it. The DNA vaccine is moving into the second phase of clinical trials with 1,000 volunteers.

ChAdOx1 vaccine: The Serum Institute of India (SII) has secured a licence for the proposed vaccine from Swedish-British pharma giant AstraZeneca, which has acquired the rights to make the vaccine being developed by a team of researchers at the University of Oxford, UK. The vaccine uses a common virus, known to cause fever in chimpanzees but is safe in humans, to contain the spike protein of SARS-CoV2 with which the Covid-19-causing virus sticks to human lung cells (causing a spate of serious respiratory problems). The early stage clinical trials carried out in other countries, including the UK, have found the vaccine to be safe and immunogenic. This has helped the SII go straight into the just-commenced Phase 3 clinical trials in India.

TV Jayan

Aye of the needle: A vaccine guide

Trial and error: Moderna’s mRNA vaccine uses novel technologies

 

Vaccination is the main defence strategy against infectious diseases caused by viruses, bacteria and other microorganisms. Conventional vaccines use pathogens (germs) which have either been inactivated or are live-attenuated (prepared with living organisms, but with significantly reduced virulence) to trigger an immune response — that is, preparing the body to respond to an impending attack by the germ. Most successful vaccines currently in use against polio, measles, mumps or rubella belong to this category.

These vaccines, however, suffer from several drawbacks. They require a large volume of pathogens. Apart from the fact that it is a time-consuming process, the method could also pose a serious threat to those involved in producing the vaccines.

Over time, however, scientists have found a way of avoiding the use of whole pathogens. They identified and isolated the proteins involved in infections, and then used them for eliciting an immune response after purifying them. With advances in science and technology, vaccine developers have started using virus-like particles that can mimic deadly viruses without being infectious.

With the spread of Covid-19, new vaccine technologies — which were in the making for long — started coming into play. These include vaccines based on DNA, RNA and even those that use harmless viruses as delivery agents. These strategies can speed up the proceess of designing new vaccines — taking months and not years like conventional vaccine technologies — and can easily ramp up vaccine production.

The proposed vaccines can be broadly classified as classic vaccine platforms and those belonging to next-generation platforms.

“We need and can make different types of vaccines. We actually need a range of ‘astras’ (arsenal) to combat this virus,” says Professor SS Vasan, who heads the “Dangerous Pathogen Team” at Australia’s Commonwealth Scientific and Industrial Research Organisation.

Some vaccine platforms — such as Oxford’s adenoviral vector — are more established, while others — Moderna’s mRNA or Inovio’s DNA vaccines, for example — are novel and exciting technologies because there are currently no nucleic acid vaccines licensed for human use, Vasan says.

But that does not mean a particular candidate is superior or inferior to another. “Such characterisation is unhelpful and premature because we need to wait well beyond Phase 3 clinical trials to assess which (vaccine) candidates work,” says Vasan, whose team was involved in the animal testing of a number of vaccines for Covid-19.

“For the sake of humanity, we need many — if not all — vaccines to succeed, and it is worth remembering that the race is against an evolving virus,” he tells BL ink .

Different vaccine types are being tried out against Covid-19. Among them are:

Whole-inactivated virus vaccine: In this, a killed version of a virus that causes an infection is used. A number of Covid-19 vaccine candidates, including three being developed by Chinese scientists, belong to this category. The vaccine developed by Chinese bio-pharmaceutical firm Sinovac is undergoing Phase 3 clinical trials in Brazil and Bangladesh.

Live-attenuated virus vaccine: This vaccine is classically produced by reducing the pathogenic properties of the disease-causing virus through cell culture. It then causes only a mild infection upon injection. The Covid-19 vaccine being developed by Indian Immunologicals Limited together with Griffith University in Australia (in pre-clinical trials) is one example of this.

Virus-like particle vaccine: This uses molecules — synthetic or otherwise — which closely resemble viruses, but are non-infectious, for raising an immune response. Since they do not have virus genetic material, they are considered safe. Many Covid-19 vaccines in the preclinical stage belong to this category.

Viral vector vaccine: These vaccines use viruses which are known to cause no harm to humans as a vector for carrying a weakened version of the virus to the cells to activate the immune system. The Oxford University-developed ChAdOx1-S vaccine, which is being manufactured by the Serum Institute of India, uses this method.

Nucleic acid-based vaccines: All living organisms carry nucleic acids — DNA and RNA — that make up their genetic material. For these DNA-or RNA-based vaccines, scientists use information from the genome of the virus to create a blueprint of select antigens (disease-causing protein). These DNA or RNA vaccines are injected into human cells for raising an immune response. The Covid-19 vaccine developed by Moderna is an example of an RNA vaccine.

TV Jayan

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