India has a long tradition of making vaccines. There is a view that ancients knew about small pox inoculation. But it was the British rule in India that helped create an infrastructure to vaccinate people. There were vaccinators or “teekadars” who went from village to village to give small pox inoculation to people for a price. This history of vaccination of masses puts India in a unique position to choose the ideal one with least side effects. For the record, India makes 70 percent of the vaccines of the world and it is in high demand to help the world beat the pandemic that has destroyed global economy, infected millions and killed hundreds of thousands of people.
Hardnews talked to experts to ascertain what kind of vaccine will work for a country that cannot create a super cold chain (-70 degree celsius) that is needed for Pfizer or is extremely expensive. The ideal vaccine for Indians had to be cheap, highly efficacious, easy to transport and with least side effects.
Initial findings suggest that all the vaccines, despite the publicity blitz, have problems. Worse, they will not be available for the poor countries as they cannot afford it. Bulk of the vaccines have been reserved by affluent west that includes: US, UK, European Union etc. Rest of the world will have to make do with Chinese, Russian and perhaps with India’s vaccine. Hence, ethical issues about private profit deciding who should be vaccinated is causing considerable anxiety in many societies. From this standpoint, India’s vaccine, Bharat biotech’s Covaxin, whose third trial is yet to be peer reviewed is still awaited, is not just rated highly, but the one which will be the most efficacious in other societies to.
Findings of the experts:
The WHO has catalogued 169 candidate vaccines for the Covid-19. Thirteen (13) vaccine candidates are being developed or manufactured in India, of which two (Covaxin and Covishied) have entered late stage clinical trials. Serum Institute (Covishied) and Bharat Biotech (Covaxin) applied for Emergency Use Authorization (EUA) of their Covid-19 vaccine to DCGI. However, both the proposals were not considered due to inadequate safety and efficacy data. The Indian arm of Pfizer also sought approval (import and market and waiving off India specific trial) for its vaccine (BNT162b2, an mRNA Vaccine) on December 4, 2020 after the firm secured clearance in the UK.
2. Covishied (SII-Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech), Covaxin (Bharat Biotech-ICMR), and Sputnik V (Dr Reddy’s-RFID) are in the most advance stage of development.
3. On December 8, 2020, peer-reviewed phase-III trial interim analysis of Oxford vaccine tested across two different dose regimens has been published by the leading medical journal Lancet. The analysis included data from four ongoing blinded, randomized, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were assigned to the vaccine or control. The efficacy data is based on 11,636 volunteers across the UK and Brazil and combined across three groups of vaccinated people. Among two groups, one received a standard dose followed by a booster dose, while the second group received a low first dose vaccination followed by a standard second dose. The peer-reviewed analysis of the trial confirmed that the vaccine protects against symptomatic disease in 70% of the case, with vaccine efficacy of 62% for those given two full doses, and of 90% in those given a half then a full dose. The overall efficacy, at least after 14 days after the second dose of the vaccine was therefore calculated to be 70.4 %. Trial’s database noted that only three cases of trial-related fever were found. No person who received the Oxford vaccine had severe disease or needed hospitalization. Of the11, 636 volunteers, only five cases occurred in those who were more than 55 years old during the preliminary analysis. The vaccine efficacy in older age groups will be determined in future analysis after more cases have accrued in this age range. It is expected that the low dose/standard dose vaccine may also provide protection against asymptomatic infection.
Note: Covishied is a weakened chimpanzee adenovirus redesigned to encode spike (S) protein of SARS-CoV-2. Adenovirus, as a vector for making vaccine is promising but yet to observe the safety of such vaccine. It usually takes 5-10 years to fully understand the safety of a vaccine.
4. The final result of the phase III trial of Pfizer’s coronavirus vaccine was published on December 10, 2020 by the New England Journal of Medicine. A total of 43, 548 participants took part in the trial, 21,720 received the vaccine while 21,728 with placebo. There were 8 cases of Covid-19 with onset atleast 7 days after the second dose. A two dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. The safety profile of the vaccine was characterized by mild-to-moderate pain at the injection site, fatigue, and headache. A case of severe Covid-19 with onset after the first dose occurred in a vaccine recipient. The vaccine has been rolled out in UK on December 8, 2020. However, it has been advised that people with a significant history of allergic reactions should not be given Pfizer/NioNTech vaccine after two healthcare workers developed symptoms after receiving a shot.
Note: Pfizer’s vaccine is based on mRNA, a first of its kind. Its safety in the long run is still unknown.
5. It is a whole virion, inactivated coronavirus vaccine (BBV152). It has undergone phase I and phase II trial and found to be safe. Phase-III trial has been initiated since November 2020 in 8000 participants and will be expanded to 40,000 participants. In the pre-clinical, phase-I and phase-II trials, the vaccine candidate was found to generate robust immune responses. Thus, preventing infection the disease upon high amounts of exposure to live SARS-CoV-2 virus. No evidence of pneumonia was observed by histo-pathological examination in vaccinated groups, unlike the placebo group. Adverse events were not seen in animals immunized with a two-dose vaccination regimen.
Note: Covaxin is developed on a time tested technique of vaccine development. Its safety in long run is reliable. However, it has yet to publish data of phase III trial.
6. The vaccine is composed of two different adenoviruses that produce the coronavirus spike protein, administered three weeks apart. Developers of the Sputnik V vaccine announced (Nov 11) phase III results, two days after Pfizer and BioNtech released the first interim evidence that a vaccine can protect against coronavirus protection. The Gamaleya National Center of Epidemiology and Microbiology in Moscow and the Russian Direct Investment Fund said that an interim analysis of 20 COVID-19 cases identified among trial participants has found that the vaccine was 92% effective. The analysis looked at more than 16,000 volunteers who received either the vaccine or a placebo, three weeks after they had taken the first dose. The trial had enrolled a total of 40,000 participants.
Note: The low number of cases reported in the Sputnik trial means that there is less certainty that the vaccine’s true efficacy is above 90%.
7. Progress status of Covid-19 vaccines being developed or manufactured in India using various platforms is appended below.
|Sl||Name of vaccine candidate||Manufacturer||Type of vaccine||Progress status||Remark|
|1||BBV152 (Covaxin), 2 doses||Bharat Biotec (BB)||Inactivated SARS-CoV-2||Phase-III trials. Applied for EUA to DCGI but not considered.||Indigenously developed by ICMR & BB|
|2||Single-dose intranasal vaccine||BB||Chimpanzee adenovirus platform||Completed pre-clinical study||Collaboration with Washington University Medical School|
|3||Covishied (AZD1222), 2 doses||Serum Institue of India (SII)||Weakened chimpanzee adenovirus redesigned to encode spike (S) protein of SARS-CoV-2||Phase-III. Applied for EUA to DCGI but not considered.||Developed by Oxford and AstraZeneca. ICMR collaboration in trials|
|4||Covovax (NVX-CoV2372)||SII||SARS-CoV-2 Protein based||Applying for Phase-III trial||Collaboration with Novavax. ICMR support trial|
|5||CDX-005, single-dose intranasal Covid-19 vaccine||SII||Weakened SARS-CoV-2||Completed pre-clinical study||Collaboration with US-based Codagenix|
|6||Novel Virus Like Particle (VLP) vaccine||SII||RBD of SARS-CoV-2 displayed in VLP||Phase –I/II in Australia||Collaboration with Spybiotech (Oxford spin-off company)|
|7||BECoV-2||Biological E||RBD of SARS-CoV-2 spike protein||Obtained approval for DCGI for Phase-I/II trials.||Collaboration with US-based Dynavax Technologies Corporation and Baylor College of Medicine, Texas|
|8||Ad26.COV2.S||Biological E||Human adenovirus-26 based||Phase-I/II||Collaboration with Janssen Pharmaceuticals|
|9||Biological E||Novel live attenuated recombinant measles viruses (rMeVs) expressing SARS-CoV-2 spike (S) protein||Initial stage/technology transfer agreement||Developed by Ohio State University College of Veterinary Medicine|
|10||Sputnik V (Gam-Covid-Vac Combined Vector Vaccine), 2 doses||Dr Reddy’s Lab||Human adenoviruses type 5 and type 26||Obtained DCGI approval for Phase-II/III trials||Collaboration with Russian Direct Investment Fund (RDIF). Vaccine was developed by Gamaleya Research Institute, Moscow. RDIF has entered separate contract with Hetero Biopharma for manufacturing Sputnik V|
|11||HGCO19||Gennova Biopharmaceuticals||mRNA vaccine||Obtained approval for Phase-I/II trials||Collaboration with US-based HDT Biotech Corporation. Funding from DBT.|
|12||ZyCoV-D||Zydus-Cadila||Plasmid(DNA) containing SARS-CoV-2 S protein information||Phase-II||Indigenous|
|13||Warm Covid-19 vac||Mynvax||Heat-tolerant version of RBD of SARS-CoV-2||Initial stage||Mynvax is a Bengaluru-based startup incubated at IISc.|