By Dr Edward Nazareth
Nov 23: As the second wave of COVID19 is badly affecting many European countries, people are pinning their hope on the vaccine as a solution to the pandemic. In India, the number of new COVID 19 cases and deaths due to COVID 19 has declined in the last three weeks and the pandemic appears to have stabilized in most of the states. However, there is a rising trend in a few states. The possibility of a second wave cannot be ruled out. If a second wave does happen, it can be worse here as well, just like in Europe. India still has a long way to go because 90 per cent of the people are still susceptible to COVID19 infections. Like the rest of the world, we too are looking for an effective vaccine which can stop the spread of this infection.
There have been a lot of reports about the success of two vaccines in the recent past. The Oxford COVID-19 vaccine that is backed by AstraZeneca and Pfizer-BioNTech’s Covid-19 vaccine are reported to be effective in more than 90% of the people who were incorporated for the trials. The early results indicate that at least these two vaccines are highly effective, several others have reached late-stage of trials, and many more are at some stage of development.
Still a long way to go
It has to be remembered that none of these vaccines are approved for use. There are lots of issues yet to be resolved.
A few more trials are required to prove that any of these vaccines are safe. The regulators must approve the vaccine before it can be given and facilities for large scale development must happen for the billions of potential doses. The researchers are yet to find out how long any possible protection may last. At least 60-70% of the global population need to be immune to stop the virus from spreading easily (herd immunity), even if the vaccine works perfectly.
There are also issues concerning the storage and transport. The vaccine developed by Pfizer-BioNTech may have to be stored at minus 70degree Celsius and once thawed it has to be used within two days where as the American based Moderna says its vaccine can be shipped at minus 20 degree Celsius and can be used for a week with normal refrigeration. The AstraZeneca-Oxford’s vaccine (known as Covishield in India), which will be manufactured in India by the Serum Institute will have to be refrigerated at 2-8 degrees Celsius. Russia’s Sputnik V vaccine stipulates storage at a temperature not higher than –18 degrees Celsius.
The vaccine doses seem to be expensive. The Pfizer vaccine costs about 20 dollars (Around Rs.1, 500) per dose and minimum two doses are required. Moderna has indicated that their vaccine will cost 37 dollars (more than Rs 2,750). Serum Institute of India has said the vaccine (Covishield) will cost between Rs 500 and Rs 600 per dose for the general public. In other parts, it is likely to cost less than 3
pounds a dose.
Success of trials and advance purchasing
The media reports of success of the vaccine are likely to be linked to advance purchasing by countries. It estimates that 6.4 billion doses of potential vaccines have already been bought and another 3.2 billion are under negotiations. The process of advance purchasing is a well established norm in the pharmaceutical industry, as it can help the development of products and fund trials. It appears there is some competition in the pharmaceutical companies to promote their vaccines. The extensive publicity in the media about the success of the trials is probably a part of the competition to promote advance purchasing.
We, the common people should not be carried away by the success reported in the trials and will have to wait for the day when a potential vaccine is available at a reasonable price. Though the political parties have promised free distribution of vaccines in the election manifestos, we know the election manifestos are promises that need not necessarily be fulfilled.
Which vaccine will be better?
Though there are several vaccine candidates, at the end of the race only three seem to have reached some conclusion. If the reported successes of trials are true, then the difference is in their method of manufacturing the vaccines, their effectiveness seem to be almost comparable. At present two modern methods are used to manufacture the vaccines.
To understand this, let me explain the basics of vaccines.
Vaccine is not a medicine that can kill the pathogen. It is a substance used to ‘educate’ the immune system of the human body to identify the pathogen and prepare ‘an appropriate weapon’ (antibody) for eliminating the pathogen. In this context, our immune system can be compared to the defense system of a country. The lymphocytes, a type of white blood cells are the soldiers of the immune system.
There is an important difference between the ‘soldiers’ of human defense system and the soldiers of any nation who defend it. The soldiers can identify the enemy easily, but the lymphocytes are to be trained to identify the enemy. If they are effectively trained, only then can they prepare the weapon called as ‘antibody’ and eliminate the specific enemy. These weapons then remain in the system for several months to years and in some cases for life.
The lymphocytes get trained for the first time when a real pathogen like COVID19 virus attacks the body. However, by the time lymphocytes identify the ‘enemy’ and manufacture the ‘antibody’ to eliminate the viruses, the viruses multiply and cause sickness.
Fortunately, the lymphocytes can also be trained if a weak or dead enemy is brought to their vicinity. The enemy may not produce the sickness, but lymphocytes prepare the weapon-antibody, which will be stored to eliminate the live enemy if they attack again. The lymphocytes can identify and prepare the antibody even if the ‘skin’ or ‘heart’ or even the ‘soul’ of the enemy is shown to them, they do not require entire body(or structure) of the pathogen. This is exactly what is done in vaccination.
Traditional vaccines: In vaccines used against measles, mumps, rubella, live but attenuated viruses of particular disease are used. In polio and rabies vaccines, inactivated (dead) viruses are used. In hepatitis B, influenza, purtusis only a small part of the virus is used.
Modern vaccines: The Oxford vaccine is made in a modern technique. Here, the enemy’s uniform is put on an ordinary civilian and shown to the lymphocyte. A civilian is brought, except for his under garments all his clothes are removed and he is dressed like an enemy. Now the lymphocyte can identify and remember how the enemy would look like.
The Oxford vaccine is manufactured by using a common cold virus from chimpanzees; about 20 per cent of the virus parts are removed. In the gap obtained in this process, the surface protein- spike protein (the uniform) of COVID19 virus is filled. Once inside a human body, these viruses do not produce sickness, but lymphocytes now know how the COVID 19 virus will look like. They prepare the antibody. Next time, when real COVID19 virus attacks, the lymphocytes will identify them by their uniform and eliminate them.
Russia’s Sputnik V vaccine is also manufactured in the same way. Here instead of viruses from Chimpanzees, two viruses that cause respiratory infections in humans are prepared and attenuated in the laboratory. These viruses do not multiply or cause sickness when injected. They are made to carry the spike protein of COVID 19 virus. (Similar to the analogy of uniform explained above).
In Pfizer-BioNTech and Moderna vaccines a different and entirely new technique for vaccine preparation is used. The lymphocytes are not exposed to virus directly, but the soul of the virus (mRNA) is injected into the recipient (human body). By using the soul of the virus, the recipient prepares the uniform of the enemy and lymphocytes will be able to identify the enemy. This enemy is incomplete and cannot do any harm. The vaccine is known as mRNA vaccine. (This analogy is to understand, it is not the exact mechanism).
It is different, because rather than having the viral protein injected, a person receives genetic material – mRNA – that is similar to the viral protein. When these are injected, the muscle cells translate them to make the viral spike protein directly in the body. The virus material is prepared inside the recipient’s body. To make it simpler, when the mRNA prepared in the laboratory is injected, it invades the recipient’s cells, hijacks the cells’ protein and prepares the spike protein of COVID19 virus. This gives the immune system a preview of what the real virus looks like. As only the part of the virus is prepared, it will not cause sickness. This helps the immune system to prepare powerful antibodies that can neutralize the real virus if the individual is ever infected.
There is a saying in moral theology, ‘end doesn’t justify the means’. But when it comes to vaccination, only the end will decide which one is better and not how the vaccine is prepared. We will have to wait and watch to decide whether the Oxford vaccine, Sputnik V vaccine are better or Pfizer-BioNTech and Moderna vaccines or some other vaccine will be better. The long term benefits and complications if any are to be studied.
COVID19 vaccines in India
American pharmaceutical company Pfizer Inc and its German partner BioNTech have claimed that their mRNA vaccine was found to be 95% effective in a late-stage trial, including in people aged over 65 years. On the other hand, Moderna Inc said its experimental vaccine, similar to that of Pfizer BioNTech vaccine was 94.5% effective in preventing COVID-19 based on interim data from a late-stage clinical trial. Both these firms have not entered into any deal with India as of now, and had it looked at any manufacturing facility.
Russia has claimed 92% effectiveness of its Sputnik V vaccine which will be marketed by Hyderabad-based Dr Reddy’s Laboratories in India. AstraZeneca-Oxford COVID 19 vaccine is reported to be better tolerated in older adults than in younger adults. It will be available from Serum Institute of India.
COVID 19 antibody has short life?
A large study from the United Kingdom had discovered that protective antibodies against the COVID 19, decline rather quickly in people who have recovered from COVID-19.
The research conducted at the Imperial College London, found that the number of people with detectable antibodies fell by about 26 percent within three months. This study supports the belief that corona virus antibodies wane rapidly, creating the risk of reinfections.
As we all know the seasonal, regular corona viruses that cause common colds that people can get reinfected over and over again. It is because people would not have protective antibodies that would last forever from natural disease. As per the data available the immunity from natural infection will not last for years and years but likely dwindle within two to three months.
As this is the case with real infection, it is very difficult to believe that the antibody from vaccines may last for long. It is not surprising that many of the researchers attached to trials of vaccines are silent on these facts.
More and more researches are needed to prove or disprove this. We may have to wait for at least one year to be sure on the longevity of the antibodies developed by vaccination.
Will these vaccines be safe in the long run?
In the recent (November 17, 2020) issue, The Lancet wrote, “Global efforts for development of a COVID-19 vaccine are yielding multiple results including some new and as yet unlicensed technologies. Reception of these vaccines by thesceptical public will challenge wide acceptance of new vaccines. Regulatory safety thresholds are a minimum bar that a product must pass to attain regulatory approval, but for the general public, cumulative safety experience will be important. Trust is earned with time, and with repeated experience. Vaccines have a long safety history, but COVID-19 vaccines are new.”
As for now, it appears that common people may not get these vaccines in the near future. By the time common people get the vaccine, in all probability, the virus might disappear by itself. Even if it persists, the long term effects of these vaccines will possibly be known.
In India Oxford COVID19 vaccine is likely to be used as it is less expensive. (Two doses may cost around Rs. 1,000). This vaccine appears to be relatively safer than mRNA vaccine. But, it is too premature to give any opinion on the safety of these vaccines.
According to Adar Poonawalla, CEO of Serum Institute of India the Oxford COVID-19 vaccine will be available for healthcare workers and elderly people by around February 2021 and for the general public by April.
It will probably take two or three years for every Indian to get inoculated, not just because of the supply constraints but because of the cost of the vaccine, logistics, infrastructure, and then, people should be willing to take the vaccine. There will be political hiccups supported by religious reasons against the use of vaccine. These are the factors that lead up to being able to vaccinate 80-90 per cent of the population. It will not be before 2024 that everybody, if willing to take a two-dose vaccine, will be vaccinated.
Not only are the efficacy and safety of the vaccines yet to be established, their availability is elusive. It may be prudent and easier to use a mask and use it properly, maintain social distance and other precautions till the virus leaves us than wait to go for vaccination.