CME INDIA Presentation by Dr. S. K. Gupta, MD (Med), FICP, CFM (France) Clinical Asst. Professor GS Medical College, CCSU, Uttar Pradesh, India. Visiting Consultant, Max Super Specialty Hospital, New Delhi.
Let us cheer the shining image of India, which not only protected its own citizens but also helped millions across the Globe by supplying vaccine doses in the hour of need, Long Live India!
How many daily Covid-19 jabs does India need to meet its December 31 deadline?
- India needs 1 crore jabs a day now to fully vaccinate the entire adult population by December 31.
- On August 27, India achieved the milestone of administering over 1 crore ( 1,03,35,290) doses breaking the previous record of 88,13,919 vaccine doses administered on August 16.
- New 1-day high of 1.28 crore jabs by India.
- 23% adult population fully vaccinated.
- India on August 31, crossed the one-crore milestone for the second time within five days as it administered over 1.28 crore doses of anti-Covid jabs till 10pm, hitting a new high in single-day vaccinations and outstripping its own previous record of 1.03 crore doses achieved on August 27.
What is the target? Why are we still running short of time?
- Central government has already set the target to vaccinate the entire adult population by December 31.
- The country has around 94 crore adult population and it needs 188 crore Covid vaccine doses to fully vaccinate them.
Is it a rational target?
- It is important to understand that this time bound target still does not include population less than 18 years of age which too needs to be vaccinated.
- On 5th September Government Union Minister reiterated to vaccinate the entire population by 31 December 2021. If it would really mean including children below 18 years of age is yet to be ascertained.
Why Govt has not included less than 18 yr. age population in the target?
- No approved trials/vaccines for children
- Since there are no approved Vaccine trials for this age group. Only Zydus CovD is approved vaccine in India for children more than 12 years of age
- Covaxin trials for children more than 2 years of age are going on with results expected to be declared in next 3 months or so.
- Worldwide too Moderna mRNA vaccine is approved in 12 year plus age group
- Mild nature of Covid in children
- Covid has been a mild disease in young population.
- Case Fatality Rate has been nearly 0.3% in children less than 10 years of age in both first as well as second wave.
- Limited production availability of currently available Covid vaccines -which are not even sufficient to fulfil adult demand.
Why is it essential to vaccinate all?
- We need to learn from other nations like USA and Israel where third wave is causing loss of life mainly among unvaccinated cohort.
- Vaccinating population is the only solution to fight the Covid pandemic.
- Also, experience and studies have shown that only complete Covid vaccination makes an individual capable of fighting the virus effectively.
- Vaccinating as much population as possible before the third Covid wave hits the country should be the objective
How many more doses need to reach target?
- As per 31 December target – total vaccination doses needed are 188 Crore. The country has already administered 63 crore vaccine doses so far.
- That means, in the next 125 days, from August 29 to December 31, India has to administer 125 crore vaccine doses to fully vaccinate the entire adult population, or 1 crore vaccines doses a day to achieve the target set.
- If the Union Minister really meant to vaccinate ‘the entire population’ it would require additional 78 crore doses for 39 Crore population below 18 years of age.
- And it would require to take the daily inoculations to about 1.5 Crore per day.
Availability of vaccines is the biggest limiting factor so far – how does India plan to get vaccine doses?
- On August 7, the central government had assured the nation that from August till December, the country would get at least 136 crore doses of ‘Made in India’ vaccines – Covishield and Covaxin.
- Additionally, India is also going to get at least 2.5 crore vaccines doses from Zydus Cadila this year. This vaccine being a three-dose vaccine would suffice for 83 lakh individuals.
- Also, another Indian pharmaceutical firm Panacea Biotech will produce 2.5 crore doses of Sputnik V in India during August, September and October.
- It means with deals finalised so far India can expect a supply of at least 141 crore vaccines from August to December. These 141 crore vaccines can fully vaccinate 70 crore individuals.
- Since these figures include about 25 crore doses already given in August, so might fall still be short of this much number in times to come.
Can there be some failures too?
- Yes. Covaxin manufacturer failed to ramp up its production capacity as projected in last few months (BSL4 issue).
- But with newer vaccines in Pipeline things can be expected to work out.
New vaccines in pipeline?
- Covavax – SII is soon expected to launch Covavax vaccine, the Indian version of US vaccine Novavax.
- Corbevax – India has a deal for 30 crore vaccines with Hyderabad-based company Biological E for its under-development Corbevax vaccine.
- Bharat Biotech’s Nasal Vaccine.
Can we hope to achieve target?
- With Serum Institute of India increasing its manufacturing capacity significantly much above the initial monthly production, there is a possibility that 1 crore vaccination a day target can be achieved.
- Rising pace in last few days has been an encouraging sign.
- So, India can be expected to get the stockpile it needs to vaccinate the entire adult population base.
What is the Govt Ideology?
“Covid-19 Public Health Response Pro-active, Pre-emptive and Graded Response guided by Epidemiological and Scientific Rigour”
- Govt is doing its part.
- Companies are ramping up manufacturing.
- Priority approvals are in place.
- We too need to contribute to this task by motivating people around to get vaccinated.
- Motivate the neighbourhood, staff and the house maids to get vaccinated.
Vaccine development – not a cakewalk
- Many vaccines failed too.
- The way New Covid vaccines are being granted Approval (Emergency Use Authorization) one after the other gives an impression that Vaccine development is a straightforward simple procedure and Governments are granting approval in haste under pressure of pandemic.
- Some people raise doubts whether some procedures are being bypassed or safety norms being compromised or corners being cut in the entire process of Vaccine development or approval.
- lt is important to look at the other side of story to realize the truth. Vaccines reaching the podium go through rigorous laboratory development based on established scientific principles. And then first subjected to animal testing for safety and immunogenicity and lastly go for human trials involving 100 people in Phase 1 and about 1000 people in phase 2 trials and larger groups involving multi-centre studies in phase 3.
Why vaccines are developing in shortest possible time during Covid pandemic ?
Because unprecedented pandemic pressure has prompted:
- Knowledge sharing.
- Scientific cooperation is at its best.
- Certain experiments are being done simultaneously rather than sequentially.
- Beurocratic red tapes have been removed.
- Government scientific institution are providing logistics, support, and materials to private partners who are pouring in money and energy.
- Ongoing pandemic is generating the perfect fertile ground for quick trials.
- Govts have supported the private companies with pre-emptive bulk orders with advance payments.
- International cooperation and support are being worked out on priority.
- However, there is no compromise in safety and effectiveness of vaccines. No corners are being cut.
Have some vaccines failed too?
- Yes. One might be surprised to know that a number of Covid vaccines in World have failed and hence withdrawn by the developers, scientists and governments. But such events make little noise so public doesn’t come to know about such failures.
- Were these failed vaccines being developed by minnows without experience or without monetary back up?
- No. pharmaceutical giants like Merck (MSD), Sanofi which own a huge experience and largest market share of non Covid vaccines in 2020 failed in Covid vaccine development.
- In 2020, GSK, Sanofi, Merck and Pfizer dominated the market with best-selling vaccines for flu, pneumonia, HPV and shingles. Among the top vaccine makers, only Pfizer has a successful Covid-19 vaccine, developed with German company BioNTech.
Why did vaccines fail?
- Different reasons such as poor immunogenicity, interference with other tests, poor efficacy, adverse side effect profile etc.
Which Vaccines failed?
Prominent Covid Vaccines that failed in last one year include:
- University of Queensland Covid vaccine from (Govt of) Australia was discontinued in First week of Dec 2020.
- Merck (known as MSD outside the United States and Canada), failed in development of Measles Virus Vector based Covid vaccine and withdrew the same on 25 January 21.
- Germany’s COVID-19 vaccine made by CureVac using unmodified mRNA failed and withdrawn in June 21.
- USA’s Altimmune Inc. discontinued its AdCovid intranasal vector-based vaccine in June 21.
- Sanofi’s failure to bring a Covid-19 vaccine to market expediently was a source of national embarrassment to France.
Why some vaccines failed? At what stage did they fail? Wrong Technology? How other researchers could carve out success using similar Idea?
First causality in vaccine development.
1. University of Queensland(UQ) Covid vaccine was Protein Subunit Vaccine called MF59 adjuvanted SARS-CoV2 Sclamp vaccine
- It was two dose vaccine being developed by Australia’s top Biotechnology company CSL Ltd. with Seqirus under guidance from University of Queensland.
- Technology: Researches used Artificial Spike Proteins (Similar to Sars-Cov-2 spike protein) and glued them together in shape of of Sars Cov 2 Spike protein using HIV glycoprotein (University of Queensland has a patented technology for this job).
- University’s presumption was that HIV glycoprotein would itself not act as immunogenic stimulus.
- However, Results of Vaccine trial showed that subjects developed antibodies to HIV Glycoprotein giving rise to False Positive HIV test.
- Why was vaccine withdrawn? If hundreds of thousands of people received the vaccine, and then began receiving positive HIV test results, this could have become a serious concern. Even if the test would later be proven to be false positive, this may nonetheless cause unnecessary stress and furore among the public.
- So the Vaccine was withdrawn after the first phase 1 trial in December 2020.This was the first causality in the vaccine development.
What were the implications of vaccine failure for rollout of Australia’s vaccine program?
- Australia had ordered 51m units of the University of Queensland/CSL vaccine, which were expected to be available from mid-2021. With that vaccine off the table, the government had to increase production and purchase of the AstraZeneca vaccine.
Currently any vaccines on this platform?
- Yes-Novavax vaccine uses natural spike protein and is phase 3 trials.
2. Merck Vaccine failure
- Technology: Merck with Sanofi used measles-virus vector vaccine called V590 and vesicular stomatitis virus(Herpes) vector-based vaccine called V591.
- Both these vectors Used Replicating Viral vectors. Both these viruses were genetically re-engineered to transmit SARS-Cov2 spike protein genetic code.
- Why Merck Vaccine Failed? In phase 1 studies, both V590 and V591 were generally well tolerated, but the immune responses were inferior to those seen following natural infection and those reported for other SARS-CoV-2/COVID-19 vaccines.
Any successful Vaccines on similar platform?
- Yes, but using non-replication Adeno virus vector.
- Covishield uses Chimp Adenovirus vector.
- Sputnik V uses human adenovirus vector Ad26 and Ad5.
- Johnson & Johnson uses Human adenovirus Ad26.
- Cansino from China uses Human adenovirus Ad5.
It was a serious setback to world’s two big pharmaceutical giants to have lost in the Vaccine Race, leading to public shame and loss in shares.
3. CVnCov from CureVac of Germany – Why did it fail?
- Technology: CureVac used an unmodified form of messenger RNA much unlike its rivals.
- While Pfizer and Moderna used modified mRNA segment which is more stable.
- Why did it fail?
- Poor Efficacy: Final trial results of CVnCoV vaccine had an efficacy rate of just 48 percent, far lower than those developed by mRNA rivals BioNTech/Pfizer and Moderna.
- Efficacy was even lower than the minimum threshold of 50% efficacy standard set by WHO.
- Vaccine performance among elderly was even poorer.
- Vaccine was slated to be stable at Room Temperature. It is to be reiterated that mRNA requires -80℃ for stability.
4. AdCovid was being developed by USA based Altimmune Inc.
- Technology: It was a vector based intranasal vaccine to be sprayed intranasally. It was adenovirus type 5-vectored vaccine encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein.
- What was it supposed to do?
- Vaccine was designed to produce Binding and Neutralizing Antibodies against SARS-Cov 2 in Blood along with Local IgA antibodies in Nose and oropharynx.
- Why did it fail?
- But AdCOVID did not stimulate an adequate immune response in healthy volunteers, though it was well tolerated. Although antibodies were detected that bound the SARS-CoV-2 Spike protein and neutralized the virus in a subset of subjects, the magnitude of the response and the percent of subjects responding to AdCOVID were substantially lower than what had been demonstrated for other vaccines already authorized for emergency use.
- Hence, based on the data, and considering the highly competitive COVID-19 vaccine landscape, Altimmune is discontinued further development of AdCOVID beyond the completion of Phase 1 trial on 29 June 2021.
- Was it a vaccine from inexperienced company?
- No Altimmune is a biotechnology company which has successfully tested NasoVAX influenza intranasal vaccine.
- Any similar vaccines on path of success?
- Yes. A similar intranasal vaccine by Bharat Biotech and University of Washington is currently in phase 3 trials in India after good immunogenicity data from phase 1&2 trails.
5. Sanofi, the big Pharma giant from France was collaborating with Merck in Vaccine development and the vaccine (as said earlier) showed poor efficacy. It brought shame to France, leading to various talks.
- No vaccine in the country of Pasteur! What a symbol. Prestigious Pasteur Institute abandoned its main coronavirus vaccine after disappointing test results.
- Technology: As described above, Sanofi France was trying to adapt an existing vaccine used against measles, in partnership with the US company Merck.
- Serious setback for France:
- The failures and delays around France’s development of a vaccine have sparked serious debate and soul-searching in the country, once a world leader in medical breakthroughs and the birthplace of microbiology pioneer Louis Pasteur, who invented vaccines against rabies and anthrax.
- The vaccine issue has touched several raw nerves in France, where some see it as an assault on the country’s self-esteem.
- Not even a single success by France Germany etc. and four Successful strokes one after the other in form of Covishield, Covaxin, Zycov D and now second-generation nasal vaccine against Covid in record time by Indian Scientist and companies can’t just be a fluke.
- It speaks volumes about the acumen, dedication and hard work of Indian Researchers supplemented by cooperation of various research institutes encouraged by the Govt of India.
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