Covid 19 vaccines are here, Is the pandemic end nearer?
Dr Asha N Shah. M. D
Professor of medicine, GCS medical college, Ahmedabad
Covid 19 is going strong and creating havoc in people’s lives but there is good news as well. OWS or Operation Warp Speed was formed in US to encourage private and public partnerships to enable faster approval and production of Covid vaccines. This name was inspired by terminology (warp speed) for faster-than-light travel which was used in the Star Trek fictional universe, evoking a sense of rapid progress. It is really astonishing to know that as of today there are 40 Covid 19 vaccines in phase1 trial, 17 in phase 2 trial, 15 in phase 3 trials,5 vaccines are in early or limited use,3 are approved and many are in pipeline. Almost 85 preclinical are under active investigations in animals. So much is being talked about all aspects of vaccines. Let us go through some of them.
Vaccine development process for testing
Preclinical Testing: New vaccine is tested by scientists on cells and it is then given to animals such as monkeys or mice to see if it produces an immune response.
Phase 1 trials: The vaccine is given to small number of people to test its safety and dosage, and also to confirm that it stimulates the immune response.
Phase 2 trials: Scientists give the vaccine to hundreds of people and they give them to various groups, such as children and the elderly, to see if it acts appropriately in them. These trials are to test the safety of the vaccine.
Phase 3 Trials: These are to see efficacy of the vaccine. Scientists give the vaccine to thousands of people and would see how many of them become infected, compared with volunteers who do not receive vaccine but receive a placebo (Inert substance). These trials are large enough and would determine if the vaccine is protective against the coronavirus and will show rare side effects also if any.
EUA( emergency use authorization): Some countries have given emergency authorization to vaccines based on the preliminary evidence of safety and efficacy.
Approval: Regulatory authorities review the complete trial results including the safety data and plans for the vaccine’s manufacturing, and then full approval is given.
Combined phases: Sometimes permission is given to carry out combined phases like many vaccines are undergoing 1/2 or 3/4 phases together.
Categories of Vaccines
There are four categories of vaccines in clinical trials:
Whole virus,
Protein subunit,
Viral vector
Nucleic acid (RNA and DNA).
Let us see the important categories of coronavirus vaccine which are either available to people or will be available in near future.
Nucleic acid vaccine (mRNA vaccines and DNA vaccines)
They are from Pfizer biontech and Moderna, both of which are already in use.DNA vaccine are in trial belonging to Zydus cadila and Inovio Company.
Viral vector
These are from Astra Zeneca from UK, Cansino from china,Gemalaya from Russia and Johnson & Johnson from USA. Out of this Astra Zeneca vaccine has been given permission and will soon be used. Russian vaccine is in use in Russia and some other countries; Cansino has gotten limited use in China .Johnson vaccine is still in trials. All of these vaccines carry Adenovirus as their vectors, which would be a modified virus (the vector) to deliver genetic code for spike proteins found on the surface of the virus, into human cells which once inside human cells, instructs them to make SARS-CoV-2 protein. This stimulates an immune response.
Inactivated vaccine (whole virus)
These are from Bharat biotech (Covaxin), Chinese vaccines like Sinopharm, Sinovac etc. in various stages of development .It is also called killed vaccine. It is a vaccine consisting of virus particles that have been grown in culture and they lose disease producing capacity but will produce immune response.( like polio vaccine ,hepatitis vaccine or flu vaccine) Whole virus vaccine can also be live attenuated.(like measles vaccine, small pox vaccine, chicken pox vaccine etc.)
Viral subunit vaccine
These are from Novavex and Vector institute (Russia) and are in trials
Rather than introducing a whole-cell vaccine (either inactivated or attenuated), a subunit vaccine contains a fragment of the pathogen and elicits an appropriate immune response. They can be of 3 types Protein based, polysaccharide and conjugate .Hepatitis B vaccine or HPV (Human papilloma vaccine) are the examples of this type of vaccine.
Vaccines available at present or likely to be available in near future
Pfizer biontech vaccine.
Pfizer and BioNtech have claimed that their coronavirus vaccine was over 90 percent effective
Dose: 2 doses, 3 weeks apart as Intramuscular injection.
Storage: Freezer storage only at (–70°C)
They have based it on a genetic molecule called messenger RNA (mRNA). mRNA carries genetic instructions for building the spike protein( coronavirus protein). When the vaccine is injected into cells, it makes them to produce spike proteins, which is released into the body and it will stimulate an immune response which includes antibodies against SARS-CoV-2, as well as immune cells called T cells .These T calls are also important for immunity. It was tested in 43000 volunteers and was also found effective in peoples of different age and ethnicity and in people with diabetes. It was given EUA (emergency authorization) in many countries of the world and lakhs of people have received it also.
The common side effects which were mild and transient and were as follows
Injection site reactions, Fatigue, Headache, Muscle pain, Chills, Joint pain and Fever.
4 people in the vaccine group developed a type of facial palsy (Bell’s palsy). This was thought to be of not much concern because it reflects the same rate in general population and is recoverable.
Moderna and National institute of health (mRNA vaccine)
Efficacy: 94.5%
Dose: 2 doses, 4 weeks apart, given as Intramuscular injection
Storage: 30 days with refrigeration, 6 months at (–20°C)
It is also given emergency approval and is being used in US and some other countries.
Viral vector vaccines
Sputnik 5
Efficacy: 92%
Dose: 2 doses, 3 weeks apart, Intramuscular injection
Storage: Freezer storage.
This vaccine is developed by Gamaleya Research Institute which is part of Russia’s Ministry of Health and it is based on two adenoviruses. Along with collaboration with Dr Reddy’s laboratory Phase 2/3 trial was launched in India in October. Russia has begun mass vaccination.
Oxford Astrazeneca SII (Serum institute of India)
Efficacy: Up to 90%
Dose: 2 doses, 4 weeks apart given intramuscularly.
Storage: Stable in refrigerator for at least 6 months
University of Oxford and the pharma company AstraZeneca have developed this vaccine. In India they have collaborated with serum institute of India and the trials have been done where it is known as Covishield.
There were some controversies regarding the conduct of the trial. The trial of this vaccine was halted for some time as one volunteer developed neurological complication. Within short time however, the trials began in all countries. All volunteers got two doses, but half strength first dose was given. What was surprising was that an initial half-strength dose supposedly led to 90 percent efficacy but the two standard-doses led only to 62 percent efficacy. Initially it was thought that the low dose version was due to mistake in measuring the dose and was not original plan for the trial. Another intriguing fact was that the low dose was only tried out on volunteers aged less than 55 years. So there were some doubts regarding the result. It seems to have cleared out and it was approved in UK before 2 days and will mostly be given permission in India too in very short time in which case it will be the first coronavirus vaccine for India.
Bharat Biotech -COVAXIN
Inactivated COVID-19 vaccine is developed by Bharat Biotech in collaboration with ICMR (the Indian Council of Medical Research) and NIV (National Institute of Virology).It has submitted data to DCGI and probably the next vaccine available in India. In India DCGI (Drug controller of India) is the body which will grant permission to all new drugs and is equivalent to FDA of USA.
ZyCoV-D ( Zydus)
Vaccine from Ahmedabad based company Zydus Cadila has also completed phase 2 trials and has been given permission for phase 3 trials. It is India’s first DNA plasmid vaccine.
Concerns in people’s mind
1) There are some concerns in people’s mind as mRNA vaccine has been available for the first time.
Moderna’s vaccine was developed within 2 days of china made the genome sequence public. But due to the regulation of completing the trails in various phases it took some months. It is still a lot faster than the usual vaccine development time. As we know designed term was OWS (operation warp speed) meaning doing various process of development together. As a result of this the vaccine development could be completed in months as compared to years. Major reason this vaccine timeline has become narrow is that much of the research and preclinical animal testing was done after the 2003 SARS pandemic. Scientists already knew to target the spike protein. mRNA is the future for developing vaccines against this type of viral diseases. In an article published in reputed standard medical journal in 20121, it is quoted that mRNA vaccines combine desirable immunological properties with an outstanding safety profile. mRNA is an intrinsically safe vector as it is a minimal and only transient carrier of information that does not interact with the genome. This is what they predicted “mRNA presents a promising vector that may well become the basis of a game-changing vaccine technology platform”. Scientists had been developing this technique since 1989.It is only now that we have better technology for this development.
People worry about possible genetic changes with mRNA based vaccine. However the idea is completely false and unscientific. It does not affect genome. The (vaccine) mRNA does not enter the nucleus of the cells, where our DNA is. There are no serious short term side effects of any of the vaccine noted. We have to watch for the long term ones which seem less likely.
2) Some people believe that vaccine contain pig, monkey or human tissues.
This is not true.
3) Another myth is that they are not safe because they are developed in such a short time. But as I said earlier, researchers had knowledge to target spike protein from previous SARS pandemic of 2003.They had already carried out research.
4) Another very important concern is that as corona virus mutates fast, so the presently available vaccine will not be effective.
The vaccine targets the spike protein and mutation has not affected it. So vaccines are likely to be effective for the present virus mutation. Recently identified mutation on spike protein called N501Y which is creating havoc in UK as its transmissibility is supposedly 70 times more. It is already now detected in many countries including India. Experts are of the opinion that the available vaccine will most likely be effective for this strain. Vaccine resistant strains are less likely to develop but if it happens in future, alteration in the vaccines can be done
When will the Covid 19 Pandemic end?
1) It is the most important question in everyone’s mind all across the world, particularly now with the availability of vaccines. Unfortunately it is not going to disappear so easily.
2) The efficacy data of all the vaccines are excellent but still we still don’t know how long the protection will last. We have to wait and watch.
3) Most of the vaccines are not recommended for age below 16 years .So the huge chunk of pediatric population will be vulnerable to get infection and they will spread the disease. Herd immunity will be difficult to achieve.
4) The vaccine will help prevent symptomatic disease in individuals but it is not same as reducing transmission. That data is still not available as vaccines have now only been given on a mass scale basis. Depending upon how much the vaccine is effective in preventing transmission; achieving herd immunity will be dependent on that.
5) There is variation in seropositivity rate in different population, which might also affect herd immunity.
6) The immunity which develops in individuals after natural infection is also not very long as observed. This could also affect the road to “END”.
7) Manufacturing and supply issues are also very major concern and in a huge country like India, to reach out to the entire population may be an enormous task.
8) People not willing to take vaccines may also remain an issue.
BUT THE PANDEMIC’S END SEEMS CERTAIN AND NEARER.
Researchers have predicted second half of 2021 for US when the cases will be low. Cases in India have already peaked at around 1 lakh on Sept.17. Government nominated expert committee consisting of scientists from different prestigious institutes of country said in their report that cumulative cases may reach 1.06 crore by end of February 2021 which may suggest that pandemic may be controlled by that time with minimum active cases. So it will not totally disappear suddenly but may be active at low level or may become endemic. We may have to take vaccine annually but that is still lot easier to manage. But one thing that this pandemic has taught us is that nothing in the world is predictable and more so as far as humans and diseases are concerned. Human beings show great courage in adverse circumstances and are resilient enough that viruses will have to retreat. Let us hope 2021 will be a better year for mankind.
References-,
1)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597572/
2)https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
