News of four COVID-19 vaccine candidates showing close to 90 per cent efficacy against SARS-CoV-2 has raised hopes of a vaccine being available soon but India has so far only signed agreements for the manufacture and/or distribution of only two of these. From the Moderna, BioNTech- Pfizer, Oxford-AstraZeneca, and Russian Sputnik V vaccines, India has only so far agreed to procure the latter two.
While the safety and efficacy studies of these four vaccines have been briefly discussed, several experts around the world have insisted that the full datasets of the findings should be awaited and analysed.
Vaccine development which is a painstaking long process has witnessed an unprecedented discovery in the fight against COVID-19 as acknowledged by the World Health Organization. For the first time ever, in a span of less than a year of a disease being declared as a pandemic, there have been over 164 vaccine candidates at various stages of clinical development. The WHO has also stepped up to co-found the ACT Accelerator and COVAX to ensure that the distribution of vaccines is equitable so that low-middle income countries can avail of it.
India which is a part of this movement is relying on both importing the approved vaccines as well as creating indigenous candidates. Serum Institute Of India is set to conduct trials for the Oxford-AstraZeneca and Novavax vaccines, Dr. Reddy's Laboratories for Russian Sputnik V Vaccine, and Biological E for Johnson and Johnson's adenoviral replicating vaccine. While trials for the AstraZeneca and Sputnik have already been approved, processes for Novavax and J&J's vaccine candidates are being planned.
Bharat Biotech's Covaxin, Zydus Cadila's Zycov D, Biological E's antigen-based vaccine, and Gennova Pharmaceutical's mRNA vaccine are being indigenously produced in India. While the first three are at various stages of clinical trial, the latter is in the final pre-clinical trials.
Indian Prime Minister Narendra Modi reviewed the country's vaccination strategy on November 24 and asked all states to provide details of frontline workers eligible for getting the vaccines as and when approved.
The National Expert Group on Vaccine Administration for COVID-19 headed by Dr. V K Paul from the Niti Aayog has suggested a strategy of vaccinating the 30 million frontline workers in the first phase. Five million doctors and nurses along with 20 million health workers, and other essential services working on the frontline will be prioritised
Vaccines Available In India
To achieve herd immunity of 60%, India needs to vaccinate close to 800 million people, virologist Shahid Jameel wrote in the Indian Express. As most vaccines are double dosage vaccines, India will need to administer close to 1.6 billion doses of whichever vaccines get approved. Depending on the number of doses available and when vaccines are approved in the country, 60% herd immunity will be achieved in India by 2021 or 2022.
While preliminary information about the safety and efficacy of the vaccines are available, their effects on different age groups, people with comorbidities, the nature and duration of immunity still needs to be studied. To understand lasting immunity, participants have to be followed up for months and years as per the vaccine protocol and its endpoints.
Several of the candidates are stored at 2 to 8º C which is in tandem with India's existing cold storage facilities.
Vaccines already under clinical trials
1. Serum Institute of India: COVISHIELD
Oxford-AstraZeneca's vaccine candidate that showed 70% efficacy is being produced by Serum Institute of India. It has emerged that the dosage regimen of one half and one full dose that showed 90% efficacy was a dosage error and was not part of the protocol.
Serum Insititute of India is conducting Phase III trials of the vaccine in India under the two full doses regimen. Priced at $3 per dose, and with all the other supply chain vaccination costs, this will be one of the most expensive vaccination programs undertaken by the Ministry of Health and Family Welfare.
A vaccine that uses a non-replicating chimpanzee adenovirus as a vector, this vaccine attacks the Spike protein of SARS-Cov-2. SII has pledged to produce 800 million doses of the vaccine by 2021, half of which will be distributed in India and the other half to the COVAX Act Accelerator.
Approval for distributing the vaccine will be sought from the Drugs Controller General of India only after Oxford-AstraZeneca receives approval from the health authorities in the UK. The vaccine had stopped trials in September after a candidate in the UK developed a reaction and were restarted in a week after it was found that the reaction was not linked to the vaccine.
2. Bharat Biotech: COVAXIN
Hyderabad-based Bharat Biotech used a SARS-CoV-2 strain isolated by the National Institute of Virology based in Pune to create its inactivated vaccine. Currently in the third phase of clinical trials with over 25,000 participants, Krishna Ella, director of Bharat Biotech stated that the vaccine will be available to use with all the necessary protocols by June 21.
The director also stated that they expect the vaccine to show over 60% efficacy but has not publicly shared its Phase I and Phase II trials. The company faced a backlash after it revealed on November 21 that a Phase I candidate had an adverse reaction. They also stated that it was not linked to the vaccine.
Bharat Biotech intends to supply 300-500 million doses of the vaccine annually.
3. Zydus Cadila: Zycov D
Ahmedabad- based Zydus Cadila has prepared Zycov D with the Department of Biotechnology and has completed the Phase II trials. The vaccine uses plasmid DNA as a vector and is expected to be in the markets by March.
No safety concerns have been raised about the vaccine.
4. Dr. Reddy's Laboratories: Sputnik V
Dr. Reddy's Laboratories is conducting Phase II/III trials of the Russian adenoviral vaccine Sputnik V in Kanpur. The vaccine developed by Gamaleya Institute and Russian Direct Investment Fund has shown 95% efficacy in its interim analysis.
The vaccine uses two separate vectors for the two doses.
So far, no adverse reactions have been reported while Russia intends to produce a total of 500 million doses of its vaccine in other countries annually.
5. Biological E: Antigen Vaccine
The DCGI approved Phase I/II trials for Hyderabad-based Biological E's vaccine that uses an antigen licensed from Baylor College of Medicine in Houston, Texas and adjuvant from Dynavax Technologies Corporation (Dynavax).
The vaccine is currently being tested on 360 participants.
Vaccines yet to undergo clinical trials
1. Serum Institute Of India- Novavax
SII will apply for Phase III clinical trials of US-based Novavax's protein-based vaccine. Phase III trials of the vaccine that used a coronavirus gene to create its Spike protein in moth cells which induce an immune response are currently underway in the UK, US, South Africa.
2. Biological E-J&J Adenoviral Vaccine
Biological E has entered into an agreement to produce J&J's COVID-19 vaccine that uses an Adenovirus26 as a vector to deliver the vaccine. As it is a replicating virus that has been chosen, the vaccine is a single dose vaccine.
J&J had to halt their trials in US in October after a participant developed an adverse reaction but restarted its trials again in November. Biological E has to seek the approval of the DCGI for this vaccine.
3. Gennova Biopharmaceuticals- mRNA
Using the mRNA technology similar to Moderna and BioNTech-Pfizer, Pune-based Gennova Biopharmaceuticals intends to produce 200 million doses of its vaccine.
Seed-funded by the Department of Biotechnology, the company is yet to begin its clinical trials.
Moderna and BioNTech Pfizer: Will India Get Access?
The Moderna and Pfizer vaccines use mRNA technology which has not been used for making any successful vaccine before.
While they have shown promising results, Dr. V K Paul had stated that India had not ventured into any agreements with the two vaccine makers.
Moderna's vaccine can be stored at temperatures matching India's current cold storage infrastructure but Pfizer requires temperatures as low as -80º C.