While 3,000 sites across India prepare to vaccinate three crore high-risk individuals, beginning with healthcare workers, from January 16, scientists and doctors are divided on the issue of restricted use approval granted to the Hyderabad-based Bharat Biotech’s Covaxin, a COVID-19 vaccine .
In a tweet on January 14, the Health Ministry said both Covishield and Covaxin approved for restricted use by the Indian regulator are safe. On Thursday, the Ministry also released a statement by four dozen scientists and doctors across India to “collectively assure” the safety of both the vaccines.
Seeking efficacy data
The statement came on the same day as 12 other scientists, including Dr. Partha P. Majumder from the National Institute of Biomedical Genomics, Kalyani, issued a statement asking for efficacy data before vaccination. The statement comes after Professor of Microbiology at CMC Vellore Gagandeep Kang told The Hindu that she will not take Covaxin in the absence of efficacy data.
While acknowledging the safety and promising immunogenicity data of Covaxin, they say: “It is imperative that relevant data from the larger Phase-3 trial become available before administering the vaccine to large numbers of people. Providing a vaccine without adequate efficacy data can lead to a false sense of security among vaccine recipients”.
They also add: “A greater degree of transparency prior to the start of the vaccination programme is essential. This is especially true for Covaxin, for which phase-3 safety and efficacy data are not yet available.”
In the statement released by the Health Ministry, the scientists and doctors agree that efficacy data i s not available for Covaxin but point out that safety parameters are very good and there is a robust immune response seen in animal studies and phase-1 and phase-2 human clinical trials. Ironically, lack of efficacy data is exactly what scientists, who have been cautioning against using Covaxin for vaccinating people, have been highlighting.
“Once the regulator based on data has approved the vaccine then who are we to object it,” asks Dr. T.D. Dogra, former Director of AIIMS, New Delhi and one of the four dozen signatories of the statement. “They have the data and guidelines and have taken a decision accordingly. We should trust the regulator and the process of vaccine approval.”
The scientists who have criticised those raising concerns about granting restricted use approval to Covaxin even in the absence of efficacy data, point out to animal and phase-1 and phase-2 human clinical trial data that shows the vaccine is safe and provides robust immune responses.
Dr. Sunil Kumar Arora from the Department of Immunopathology at PGIMER, Chandigarh, and one of the scientists who signed the statement, told The Hindu that even robust immunogenicity data from phase-2 cannot be used as a substitute for efficacy data from phase-3 trial.
“In an emergency situation, the regulator is convinced that the data submitted is sufficient for approval. Who are we to question the regulator,” says Dr. Dogra. “Many drugs are regularly approved by the regulator. Why object only to this vaccine approval?”
However, Professor of Physics and Biology at Ashoka University Dr. Gautam Menon, who is also co-author of COVID-19 modelling studies, said in an email, “Even robust immune response data from human participants cannot be a substitute to efficacy data collected during phase-3 trials.”
In response to the accusation that “reprehensible utterances are causing huge credibility crisis for the Indian scientific community”, Dr. Menon said: “The statement of the group of 49 doctors and scientists uses politicised language, talking of “vested interests”, “defamation” and “irresponsible statements”. But to talk of the need for safety in a vaccination program where many hundreds of millions of healthy people will be vaccinated is none of these, even as the fact that Indian companies are at the forefront of vaccine development is a source of pride.”
But Dr. Dogra says: “People with certain intentions don’t want people to get vaccinated and so are dividing people. They are biased and want to create confusion in people so they don’t get vaccinated.”
On the other hand, by not waiting for efficacy data from phase-3 trials, the Indian regulator has bypassed the approval process even for restricted use, says Dr. Aniket Sule from Homi Bhabha Centre for Science Education at Mumbai’s Tata Institute of Fundamental Research (TIFR). “Questioning the approval process by the Indian regulator does make anyone anti-Indian scientists,” Dr. Sule says.
Scientists supporting the approval of Covaxin say that the use of a whole virus inactivated vaccine which may have better protection even against mutant strains of the virus as the immune response will be against multiple antigens and not only against spike protein. “This vaccine has thus been approved under clinical trial mode keeping in mind the spread of mutants strains speeding in India from Britain and South Africa,” the scientists say.
“The whole virus that has been inactivated is used in Covaxin. Such a vaccine will produce an array of antigens that will elicit higher and stronger immune responses. So there is a biological reason for saying inactivated virus vaccines will be more effective against mutant strains,” says Dr. Samiran Panda, Head of the Epidemiology Division at the Indian Council of Medical Research.
“The whole virus that is inactivated will induce immune responses to all components of the virus unlike vaccines that use only the spike protein,” says Dr. Arora. “That immune responses to other components can neutralise the virus, including mutants, is theoretically possible. But we can’t say with certainty till we have evidence.”
“The statement that COVAXIN might be more effective against new strains of the virus is, as far as I can see, a speculative one which is not backed so far by data,” says Dr. Menon. “Human biology is complex and inactivated whole-virus formulations could potentially produce what is called antibody-dependent enhancement, exacerbating the disease. This is where good efficacy data and follow-up is crucial.”
But so far, no large-scale whole genome sequencing of the virus isolated from people testing positive has been done to say whether the mutants spreading widely in Britain and South Africa are indeed becoming more widespread in India.
The National Task Force (NTF) on COVID-19 recently wanted whole genome sequencing to be done for 5% of the positive cases from all the States and Union Territories. With 15,000-17,000 fresh cases detected daily in India, genome sequencing is far from reaching 5% of positive cases detected across the country.