Second wave, new vaccines mark India’s summer of disquiet

After a five-month downward trend in the number of coronavirus cases, a second wave of infection that started gathering steam in mid-February 2021, has now seen India cross the one million active cases mark again, prompting the government to implement urgent measures to check the spread of the virus.

The daily case numbers in India had gone down to below 9,000. The sharp increase to lakhs, which the government attributes to people's fatigue of and non-adherence to COVID-appropriate behaviour, was spotlighted by a record 1,45,384 fresh cases on April 10. The numbers have been increasing every day since (with a total number of reported cases of more than 14 million by 15 April 2021).

Though the government maintains that the spike was because of peoples’ laxity, key government representatives permitted and participated in massive gatherings such as election rallies in several poll-bound states and mega religious congregations like the Mahakumbh Mela , which saw more than three million pilgrims throng the holy city of Haridwar. Many state governments – including worst-hit Maharashtra, Kerala, Karnataka, Tamil Nadu, Andhra Pradesh, Delhi and Uttar Pradesh – have imposed restrictions such as partial lockdowns and weekend or night curfews to limit gatherings.

The curve of the second wave is steeper than the first, says Preeti Kumar, Vice President of public health system support at the Public Health Foundation of India. Though the virus has not spread uniformly across states, the number of cases within a given period of time are far more than that in the first wave that peaked in September 2020. “And we should understand that we have not yet reached the peak,” she says.

Though genome sequencing efforts do not show any local mutations driving the epidemic, more work is needed to draw a conclusion, Kumar says.

The country claims a robust vaccination graph – the fastest to have reached the 100 million vaccination mark in 85 days bettering the US (89 days) and China (103 days) – though experts say for the population size of India, this is just a trickle. “The only way to overcome this is to open more vaccination points, increase their efficiency, ensure uninterrupted supply and most importantly convince people to take the vaccine,” says virologist Shahid Jameel, Director of the Trivedi School of Biosciences at Ashoka University in Sonepat, Haryana.

In his public messages, India’s Prime Minister Narendra Modi stresses the need for creating micro-containment zones and extensive testing to combat the second wave. He also launched a “vaccine festival” between April 11 and 14 to boost the number of inoculations.

India has been administering around three million doses a day, a small number considering its mammoth population of around 1.40 billion. Several states in the county are reporting a scarcity of vaccines although the central government denies any shortfall. “There is no scarcity of vaccines in the country,” Union minister Harsh Vardhan said.

In order to give more momentum to the vaccination drive, India needs to saturate districts that have higher number of cases. “Preventive measures should be enforced in the adjoining districts that have a potential for the epidemic,” Kumar says. For this to happen, both vaccine production and distribution need significant scaling up.

Vaccine supply and pipeline

On 13 April 2021, India decided to grant emergency licensure to vaccines authorised for use in the US, UK, Europe, Japan or by the World Health Organization (WHO). The move comes at a time when India is facing a vaccine shortage and is struggling to meet growing demands. Under the new norms, instead of conducting a local clinical trial before seeking an emergency licensure, the companies can conduct a bridging trial parallel to the roll-out post-authorisation. The first 100 beneficiaries of such foreign vaccines will be assessed for seven days for safety outcomes before they are rolled out in the country.

Within one year of the pandemic, vaccines by two Indian companies – Serum Institute of India and Bharat Biotech – were approved for emergency use in India. A third vaccine Sputnik V , developed by Russia's Gamaleya Research Institute of Epidemiology and Microbiology and manufactured by Dr. Reddy's Lab in India, was also approved for emergency use on 13 April 2021.

The Sputnik vaccine has two different adenovirus-based vectors, each carrying SARS antigen, one for the first and one for the second dose. “The two doses make high levels of antibodies,” says Polly Roy, a professor of virology in the Department of Infection Biology at the London School of Hygiene and Tropical Medicine. “Because of the use of two different vectors for two doses, this vaccine may be more effective,” she says.

Several others – Zydus Cadila's DNA vaccine, Gennova's self-replicating RNA vaccine, Premas Biotech's recombinant 3 antigen vaccine – are in various stages of development. Besides this, some Indian vaccine companies have manufacturing partnerships with overseas developers, the most prominent being two of Biologicals E with Johnson & Johnson and Dynavax, and Serum Institute of India with Novavax.

Some other interesting leads are in early stages of development, including the indigenous thermostable protein-based candidate from Mynvax, and the US-licensed nasal adenoviral vaccine candidates.

"Vaccine development in India has done reasonably well especially on the technology transfer needed for making vaccines – both viral vectors and protein-based ones as well as the inactivated Covaxin," says virologist Gagandeep Kang, a professor in the Department of Gastrointestinal Sciences at the Christian Medical College, Vellore. “But in terms of developing new candidate vaccines in India, there is still a lot of scope for improvement,” she says.

Indian companies have been quite successful in licensing COVID-19 vaccines from across the world for manufacture. The regulatory authorities have also been responsive to the challenges of emergency usage authorisation, says immunologist Satyajit Rath, a visiting faculty at the Indian Institute of Science Education and Research (IISER), Pune.

Epidemiologist Lalit Kant, a former Head of Indian council of Medical Research’s (ICMR) Division of Epidemiology and Communicable Diseases, says India has lived up to its image of being the world’s pharmacy. Of the 30 Indian companies which launched vaccine development programmes, some have been in collaboration, while others were manufactured in India under license, he says. “This landscape is very dynamic, and new collaborations are reached very frequently.” The government’s 2021-22 budget has also earmarked Rs 900 crore for vaccine research in the country, he adds.

The deep penetration of the primary health care system and a legacy of maternal and child health immunisation drives have been pivotal in the vaccine rollout programme in India, says Sanghamitra Pati, a physician turned public health researcher and Director of the ICMR Regional Medical Research Center Bhubaneswar.

Affordability and equity in vaccination access at a global scale will be pivotal to arrest the spread of the virus. “India is best positioned to produce the volumes required for the world at an affordable price – it is a good sign of our science and technology strength,” says Anurag Agrawal, Director Institute of the CSIR-Institute of Genomics and Integrative Biology.

Regulatory environment

Rath says the lack of transparency in India's regulatory ecosystem resulted in the premature approval given only to the indigenously developed vaccine Covaxin, while deployment of public funding for vaccine development remained sub-optimal. “The supply of an optimally growing SARS-CoV-2 virus culture by the Indian Council of Medical Research to Bharat Biotech for 'Covaxin' development was a low-hanging fruit, regardless of whether the supply is enough to make a major impact or not.” On the other hand, Rath points out, vaccine development efforts of other researchers in publicly funded institutions were not well supported by the government.

Gautam Menon, professor of biology and physics at Ashoka University, agrees. “The process of regulatory approvals should be seen to be independent and transparent. While the National Technical Advisory Group on Immunisation in India (NTAGI) was envisioned as an independent, advisory body, the decisions to accept or reject its recommendations are hemmed in by the involvement of a variety of government agencies.”

A lesson for future pandemics, Menon says, is that the process of vaccine approval should be more transparent. While there should always be space for emergency use authorisations under appropriate circumstances, the public should be convinced that no political element influences these decisions.

India must align with global best practices, says Jameel. “For example, the composition of the Subject Expert Committee of the regulatory body is not public knowledge. On the other hand, US FDA held an open hearing for its vaccine approvals.”

The circumstances surrounding both Covishield and Covaxin approvals were opaque. The same metric is also being applied to the Johnson & Johnson and Sputnik V vaccines, he rues.

Kang says regulators must assure people that the products they approve are safe and efficacious. “While speed of the trials is important, the role and responsibilities of the regulator do not change. Regulation charts out a pathway for developing the vaccine and therefore the conduct of clinical research needs to be made robust.”

The trials in India were done within the stipulated framework of what the regulator required. “But there were some issues reported in the media about how the trials were handled, particularly with regard to consent and communication,” Kang says.

The WHO has developed a concept of medicine procurement decisions and is now recognised by the international regulatory and procurement community.

The WHO considers 35 countries ‘stringent’ according to its Stringent Regulatory Authority (SRA) guide. The Russian, Chinese or the Indian regulatory authorities do not figure on this list. Incidentally, these countries have given emergency use authorisation to vaccines developed in their own country without data for Phase 3 trials. “We need to urgently raise the capacity and capabilities of the India regulator to figure in the SRA list,” Kant says.

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