By Dr Edward Nazareth
Jul 21: With the start of the onset of the spread of COVID-19 from China to other countries, the discussion about an effective vaccine against this highly infective virus had started and is still going on. There are several reports that a vaccine is almost ready to use, but so far, no authentic or approved vaccine is available against COVID-19 for use. We are not sure when a vaccine will be available either. Meantime, some basic information about vaccines and related issues may be of interest.
How does the vaccine work?
To understand the basics about vaccination we may have to understand a little about our body’s immune system. The immune system is a defence mechanism of the body, which can be compared to the military of any nation. Like a nation’s military system the immune system of our body is capable of identifying the intruder, marking the intruder as ‘enemy’, preparing a suitable weapon to eliminate the enemy, remembering the enemy and, fighting to protect the body from an attack by the same ‘enemy’ again. In medical terms, the ‘marked enemy’ is known as antigen and the weapon prepared to eliminate the enemy is known as ‘antibody’. Every individual’s immune system is unique and works in almost a similar way.
The weapons that are needed to eliminate the enemy, the antibodies are very specific to the antigen; for example, the antibodies against COVID-19 can eliminate only COVID-19 viruses and not any other virus or bacteria. Similarly, the antibodies against the measles virus can kill only measles viruses. The immune system needs some time to identify the enemy and produce antibodies to eliminate it. Vaccination is a process by which the immune system is trained to identify the enemy in advance, far before the attack by the enemy, to produce the antibodies and to eliminate the specific enemy without causing harm to the body.
In case a person is infected by COVID-19 virus, the immune system identifies the virus as an ‘antigen’ and develops antibodies to eliminate it. But, it takes time and by the time the antibodies are produced the virus would have done harm. If the immune system was alerted earlier and had been informed to produce antibodies, the immune system would have eliminated the virus before it attacked the vital organs.
How can the immune system be alerted earlier?
This is done by vaccination. The vaccines contain the same germs that cause disease. For example, the measles vaccine contains the measles virus, and polio vaccine contains the poliovirus. But in these vaccines, the infective pathogens are either killed or weakened to the point that they do not make the vaccinated person sick. It is like training the military to identify the enemy by showing their uniform or flag. Then the military can identify the enemy early on and deal with them without having to fight a war. The immune system would do the same thing when vaccinated.
A vaccine stimulates the immune system to produce antibodies, exactly like it would if one were exposed to the organism causing the disease. After getting vaccinated, the person develops immunity to that particular disease, without suffering from the disease. He/She has antibodies circulating in the system, specific against the organism. Therefore a vaccine can be thought of as a powerful medicine. Unlike most medicines, which treat or cure diseases, vaccines prevent them.
A vaccine to prevent COVID-19 is perhaps the best hope for ending the pandemic. However, we have no effective anti-viral medicines to kill the virus or stop its multiplication in the body so far and it is unlikely that we will get one soon. Moreover, most of the antiviral medicines are too expensive and have a lot of side effects. So far an effective vaccine to prevent infection with the COVID-19 virus is not available to use, but scientists are racing to create one. Some positive reports are just available about a vaccine prepared by Oxford University.
COVID-19 viruses have a spike-like structure on their surface called an S protein. (The spikes create the corona-like, or crown-like, an appearance that gives the viruses their name.) The S protein attaches to the surface of human cells. A vaccine that targets this protein would attack the COVID-19 viruses the moment they enter the human system preventing it from binding to human cells and thus stop the virus from reproducing.
As mentioned earlier, the main method of preparing the vaccine so far is using the original virus. The measles, mumps and rubella (MMR) vaccine were made by using weakened viruses that cannot cause a full-blown infection. The seasonal flu jab takes the main strains of flu doing the rounds and completely disables them similarly.
Some researchers are using a new approach called 'plug and play' to prepare a COVID-19 vaccine. As the genetic code of COVID-19 is known and it is possible to reproduce it, the researchers in Oxford have put small sections of its genetic code into a harmless virus that infects chimpanzees. They hope to have developed a safe virus that looks enough like COVID-19 virus but is harmless and if introduced into the human system, can produce an immune response.
Other groups are using pieces of raw genetic code (either DNA or RNA depending on the approach) of COVID-19. Even if this is injected into the body, it will produce bits of viral proteins which the immune system can learn to fight. However, this approach is completely new.
Safety evaluation needs years
In a normal course, it takes several years, sometimes decades before any vaccine is introduced for use. Before a vaccine is ever given to people, extensive testing of the vaccine is done in laboratories. This can take several years to make sure it is safe and effective. After this, testing in people begins, and it can take several more years before clinical studies are complete and the vaccine is licensed. Once a vaccine is licensed, the authorities routinely monitor its use and investigate any potential safety concerns.
Before a vaccine is approved for use in the United States, it goes through years of careful testing to make sure it is safe and effective. Highly-trained researchers at the US Food and Drug Administration (FDA) evaluate the results of the clinical trials. FDA also inspects the laboratories where vaccines are manufactured to make sure they follow strict manufacturing guidelines. Once a vaccine is licensed, the FDA and CDC continue to monitor its use and make sure there are no safety concerns.
Even if the research groups design a potential COVID-19 vaccine, there is much more work to do.
• The trials need to show that the vaccine is safe. It would not be useful if it caused more problems than the disease. Multiple trials are required.
• The clinical trials have to show that the vaccine provokes an immune response which would protect people from getting sick. The antibodies should ideally remain in the system for several years.
• A way of producing the vaccine on a large scale must be developed for the billions of potential doses. The health authorities and regulators must approve it before it can be given.
• Finally, there will be a huge logistical challenge of actually immunizing the population. To control the pandemic about 60-70% of people need to be immune to the virus in order to stop it spreading easily (known as herd immunity). But that would be billions of people around the world even if the vaccine worked perfectly.
When we will get COVID-19 vaccine?
Although there are reports that a vaccine would be available soon, reality seems to be different. An effective and safe vaccine may not be available before the end of 2021.
Researchers all over the world are working around the clock to find a vaccine against the COVID-19 virus. Experts estimate that a fast-tracked vaccine development process could speed a successful candidate to market in approximately 12-18 months –- If the process goes smoothly from conception to market availability. Important research developments are mentioned here.
A group in China showed a vaccine that was safe and led to protective antibodies being made. It is being made available to the Chinese military.
Finally, some positive result about COVID-19 vaccine is announced by the University of Oxford.
According to the reports, the vaccine developed by it against COVID-19 has shown positive results in the initial trials. Officially known as AZD1222, the vaccine has been developed by the Jenner Institute, a part of the Nuffield Department of Medicine at the University of Oxford. The formulation is backed by AstraZeneca PLC, a British-Swedish pharmaceutical company. According to media reports, this vaccine may provide 'double protection' against the coronavirus. The vaccine might trigger the production of antibodies and killer T-cells in the body. So there is a chance that the new vaccine may be able to provide immunity against the virus. The killer T-cells are said to last much longer in the human body; they recognize and kill the virus-infected cells in the body, preventing the infection from growing. This may have some significance if the protective antibodies in COVID-19 patients disappear within a few months. Serum Institute of India has joined British-Swedish drugmaker AstraZeneca to manufacture and supply the vaccine being developed by the University of Oxford. Recently the chief executive officer of Serum Institute of India had said that it would take at least 6 months to provide this vaccine in India after it was approved for use. This vaccine needs further trials and approval by the authorities before it will be made available in the United Kingdom. Then there may be a time gap before we get it in India.
The OWS-Operation Warp Speed (OWS) is a collaboration of several US federal government departments including Health and Human Services and its sub-agencies. It has partnered with more than 18 biopharmaceutical companies to accelerate the development of drug and vaccine for COVID-19 in the USA. The US government is choosing three vaccine candidates to fund for Phase 3 trials under Operation Warp Speed: Moderna’s mRNA-1273 in July, The University of Oxford and AstraZeneca’s AZD1222 in August, and Pfizer and BioNTech's BNT162 in September. It may take 1 to 2 years before a safe vaccine is made available.
WHO (World Health Organization) is starting a vaccine program with two other organizations Gavi and CEPI. Gavi, the Vaccine Alliance started in the year 2000, is a public-private partnership that helps vaccinate half the world’s children against some of the world’s deadliest diseases. CEPI is an innovative partnership between public, private, philanthropic, and civil organizations, launched at Davos in 2017, to develop vaccines to stop future epidemics. The goal of this program is to deliver two billion doses of safe, effective vaccines that have passed regulatory approval and/or WHO prequalification. But the vaccine will be available only by the end of 2021. These vaccines will be delivered equally to all participating countries, proportional to their populations, initially to healthcare workers and then to the vulnerable
population of participating countries.
COVID-19 vaccine in India
India is also making significant progress in producing an indigenous coronavirus COVID-19 vaccine. Indian Council of Medical Research (ICMR) has urged the medical institutions across India to expedite the clinical trial approvals for Covaxin-the vaccine against COVID-19. ICMR is developing the vaccine in collaboration with Hyderabad-based Bharat Biotech and the National Institute of Virology (NIV). So far, few clinical sites have been identified and the clinical trial process has just begun. The clinical trial COVID vaccine has been termed as ‘top priority project’. However, it is not known when a safe and effective vaccine will be available. When the organizations in other countries which have finished initial phases of clinical trials are not able to predict when their vaccine may be available, it is too premature to expect an early vaccine in our country where the clinical trials have just started.
Limitations of COVID-19 vaccine
- Do antibodies have a short life?
As the COVID-19 infection is new, we are yet to learn many aspects of this disease. It is not known definitely how long after infection the antibodies will last in the body. Some of the vaccines do give protection for life. For example, the MMR vaccine is very effective at protecting people against measles, mumps, and rubella, and the people who have received two doses of MMR vaccine as children are usually considered protected for life and don't need a booster dose. But all vaccines do not give lifelong immunity. For example, the vaccine against whooping cough gives protection for about 4 to 6 years. Tetanus vaccine gives protection for 13 to 25 years. Hepatitis B vaccines protect for nearly 20 years after vaccination. It means, after a certain period the immune system of the body does not produce antibodies or the antibodies disappear after that.
Another good example is the flu vaccine. The annual flu shot is believed to be the best line of defence, and vaccination every year is recommended because the flu virus is in a constant state of adaptation and mutation, rendering older vaccines obsolete.
Recently published studies state that the antibodies formed against COVID-19 infection begin to decrease in number just two to three months after the infection. This is an important observation; it means to state that the following vaccination the antibodies may not last for long.
A paper titled ‘Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 (COVID-19) infection’, by King’s College London researchers, analysed the immune response of more than 90 patients and healthcare workers at Guy’s and St Thomas’ NHS Foundation Trust, the London hospital which had treated Prime Minister Boris Johnson after he tested positive for coronavirus in March. They observed that people produce a reasonable antibody response to the virus, but it was waning over a short period of time and depending on how high the peak was, that determines how long the antibodies would be available.
If a full-blown infection with the COVID-19 virus produces antibody levels that wane in two to three months, the vaccine will potentially do the same thing. People may need repeated vaccination (booster doses) and one dose may not be sufficient. However, it is premature to conclude this and more studies will be needed.
The COVID-19 virus is more dangerous to people with low immunity. In those with good immunity, the virus may not even produce symptoms. They may not require vaccination now.
The use of COVID-19 vaccine against the elderly and other people with low immunity is yet to be established. The vaccination against COVID-19 will, almost inevitably, be less successful in older people, because aged immune systems do not respond as well to immunization. This is also seen with the annual flu jab. It may be possible to overcome this by either giving multiple doses or giving it alongside an adjuvant that gives the immune system a boost. It might take years before a proper safe solution is available.
If a vaccine against COVID-19 is developed, then there will be a limited supply, at least initially, so it will be important to decide whom to administer it to. Healthcare workers who come into contact with COVID-19 patients would top the list. The disease is most deadly in the elderly so they would be a priority if the vaccine would be effective in this age group.
As stated earlier, the COVID-19 infection is new, we are yet to learn a lot of issues regarding its infectivity, course of illness and possible remedies. The vaccine is thought to be a solution to the pandemic, but we are not sure when we will get an effective vaccine. And once available we may have to wait and observe for the effectiveness of such a vaccine. All the hype created by the vaccine also might wane like the antibodies it would produce, we have to wait and watch.