This question can also be put as: Why vaccine takes such a great deal of time to develop?
Yes, seriously. Why do researchers and scientists take such a long time to develop vaccines while people are dying in mountain numbers? For SARS-CoV-2 it took almost a whole year to develop a single vaccine and yet we are hearing that new viruses are coming up making it further hard to be killed. To know more about it, click here.
In this article we are going to explore this very thing with some other related and interesting questions.
After exploring, we can answer:
- Why does vaccine takes years to develop?
- How do we have covid vaccine after 1 year?
- Vaccine development phases
- What is Emergency Use Listing formed by WHO?
- Efficacy of the some important vaccines.
Well, if you think one year is a lot then you might get surprised when I tell you this. ‘Developing a vaccine takes at least decades to develop.’ The key word(s) is(are) ‘at least’ and yes, it’s not even a joke. You don’t believe me? Okay, let us take an example:
Just consider Human papillomavirus(HPV):
- Naked DNA virus.
- Transmit through skin-to-skin contact (by touching warts) or sexual intercourse with infected person.
- Causing warts (dry, small grainy skin growths on soles and fingers) and cancer of vagina, penis, cervix, anus or throat.
- No treatment available or needed mostly. Cancers are treated by combination of therapies such as radiation, chemo or even surgery.
- Its vaccine took 26 years to develop.
Therefore, considering this, we even have a vaccine after one year is a marvel in itself.
But still, it strikes a question.
Why, why years just to develop a vaccine?
Here, we are actually talking about the steps and processes of vaccine development. Hence, without delaying a bit, let’s just go through all of the processes that are involved.
Vaccine development consists of 3 main phases which are associated with human trials, along with laboratory and animal studies that are performed prior to these 3 phases. There is also a phase IV in the last which is optional.
Allow me to go through each stage, one by one. First is:
- These are performed ahead of the human trials.
- In this, laboratory studies are carried out on antigen or weakened viruses. These are those viruses that might help in fighting off the disease.
- This stage takes more than a year to complete.
- In this, studies are performed on cell cultures and animals like on mice or primates.
- Here, the animals are ‘exposed’ to target pathogen/antigen.
- Provides some idea on immunogenicity and cellular response possible in humans.
- Provides data of safe dosing for the next stage.
- It is the stage where many of the candidate vaccines fail to produce the expected outcome and the stage where they are modified into more adaptive vaccines.
- Also takes 1-2 years.
Q#1: What is a simple difference between antigen and pathogen?
A#1: An antigen can be anything that induces our immune system to produce antibodies against it.
- Eg- Pathogen such as bacteria and viruses, toxin, allergen etc.
- These can be protein, lipids or polysaccharides.
Pathogen is an organism that causes disease and posses these antigens.
- These are mostly microbes like bacteria(living), virus(non living outside body) and protozoa (Eg- Plasmodium causing one of the most common infection in human i.e. malaria).
- They have antigens on their surface for specific recognition.
Phase I of human trial:
- Dosages are given to small groups, may be, of less than 100 volunteers that are healthy and are adult.
- In this, further studies are done about the immune responses, dosage and safety of the vaccine by observing the volunteer hence this phase is also known as by ‘Safety trial‘.
- Sometimes, volunteers are exposed to weakened pathogen and supervised carefully within controlled conditions.
- Several hundreds of volunteers take part. They may belong to the same age, group and sex as that of target audience on which the vaccine after successful trials are going to be introduced.
- This is done to know about the immunization schedule, delivery method and further evaluation of similar studies as that of phase I.
- A group without the vaccine is also monitored to be compared with that of vaccinated volunteers.
- Now after promising results, the candidate vaccines are tested on large scale i.e. participants in thousands of number which can belong to different cities or even countries.
- Participants can be chosen that are already diseased or after introducing the vaccines, participants are looked forward for natural exposure of pathogen.
- This stage, also 2nd, follows a double blind method (A#1).
- It is the longest phase, can take years to follow up.
A#1. Double blind method: In this, neither the participants nor the scientists know who are given the actual experimental vaccines or who are given the placebo (saline solution, no drug) and by whom. This is important to shield any psychological influence or biasing on their assessment.
After passing all the phases successfully, there is a regulatory body that:
- Checks vaccine safety and manufacturing quality.
- Inspects drug developing facility.
- Some National Regulatory Authorities (NRA) of these countries are
- India- Central Drugs Standard Control Organisation (CDSCO)
- Unites States- Center for Biologics Evaluation and Research (CBER) under Food and Drug Administration (NRA)
- China- China Food and Drug Administration (CFDA)
- Canada- Health Canada Federal Body (HCFB)
- UK- Medicines and Healthcare products Regulatory Agency (MHRA)
- Russia- Ministry of Health (Minzdrav)
- Australia- Therapeutic Goods of Administration (TGA)
- Saudi Arabia- Saudi Food & Drug Authority (SFDA)
- Then the vaccine is sent for licensing which can takes another set of years to follow up.
Q#2. What are some of the important drug/vaccine that failed in Phase III?
A#2. If we are talking about failing of some drugs/vaccines then what are they? Here are two of the important examples to know.
- V710 vaccine:
- Purpose- To prevent Staphylococcus aureus infection (causing agent of life threatening septic shock).
- After successful results in phase II, in phase III it didn’t provide results according to the expectation. It was not efficient and also poses some serious concerns to the patient health and life.
- Purpose- To treat negative symptoms of Schizophrenia (mental disorder causing delusions, disorganized speech etc).
- Failed to improve negative symptoms (antisocial, lack of empathy etc) of schizophrenia.
- The optional but recommended phase.
- After license approval, the quality control and production of vaccine is still monitored.
- Manufacturer monitors drug performance in general population, their risks and benefits in real life scenarios.
- Sometimes, rare side effects are noticed.
- For safety measures, drug can also be withdrawn from the market.
- Eg- Avastin, for metastasis i.e. breaking of cancer cells and spreading to different regions of body in breast cancer treatment. Even after satisfactory outcomes in phase III, after studies showed no significant improvement of metastatic control.
After going through all this, you may have gotten a fare idea of how and why vaccine takes such a long duration.
But it further strikes another question that has serious concern.
If it’s really true that vaccine take years to develop then how come we got Covid19 vaccine in about a year?
It is good that we have vaccines but now it imposes lots of questions on their safety. Isn’t it?
Well, it does. But we have to remember. It is not some mundane circumstances. As soon as the pandemic broke out, the whole world worked together. The vaccines trials were going on simultaneously throughout the world. Researchers and scientists throughout the world were communicating and sharing their data, analysis etc. Besides, doctors and scientists were and are working tirelessly throughout day and night. Also, funding was provided in advance by governments to manufacture vaccines. Here is a direct link to WHO where more is described on the topic.
But most important point here is that in actuality we already had some knowledge about SARS-CoV-2. How? Well, you may have noticed its name- ‘Severe Acute Respiratory Syndrome Coronavirus 2’. This simply means we have its predecessor with us long before.
History of coronavirus
In 2002, a new disease named SARS first reported in Guangdong province of China. It can be considered as first pandemic of the century. However, it was miniscule in comparison with the pandemic now.
It spread to less than 30 countries with less than 10000 cases and 1000 deaths were reported. It would be havoc then but who would have known it was a teaser for 20 years later showdown. At that time, it was controlled within 7 months and last case was reported in 2004.
MERS, Middle East Respiratory Syndrome that was first reported in Saudi Arabia in 2012. It was originally founded in bats but mainly transmitted by camel, hence disease is also known as ‘Camel disease’. There are still active cases in 2021. To know more about them, click here.
The common thing in all these including covid19 is that they belong to virus of same family, Coronavirus. It is an RNA virus causing respiratory related conditions in humans and birds. (More about them in previous blog)
Hence we had a fair idea about their structure, life cycle, diseases etc.
In short, you must know, ‘no one can skip a single step’ as it would affect the efficacy of the vaccine and trust of the people itself.
Also, for time like this, WHO has created EUL(Emergency Use Listing).
What is EUL?
- It is a procedure that evaluates unlicensed vaccines on basis of risk vs benefits.
- The data of a vaccine are compared among experts of WHO for safety, efficacy and quality.
- This makes the vaccine approach public sooner than the time which could have taken in normal conditions.
- The listed vaccine is permitted to be used by countries in case of emergency, as in right now.
As we have discussed about vaccine development. Now let us look at the efficacy of some of the known vaccines.
- Effective against almost all first 4 variants that are Alpha i.e. B.1.1.7(1st reported in UK), beta i.e. B.1.351(1st reported in South Africa), gamma i.e. P.1(1st reported in Brazil) and delta i.e. B.1.617.2(1st reported in India).
- FDA approved it for emergency use in children from 5-15 years and people above 16 years are fully approved.
Though, Israel is showing some new trend for the same.
AstraZeneca/Covishield: Above 70%.
- Also effective against all 4 variants.
- For age groups above 18 years.
- It is quite similar to Pfizer, though storing it is very easy as it is stable at -40oC, where Pfizer need -70oC.
- For age groups above 18 years.
Sputnik V: Around 80%
- For age groups above 18 years.
Covaxin: 78% to 100% depending on mild to severe infection.
- It is more effective on wild(original) variant than the delta.
- Emergency approved for children aged from 2-18 years.
So, I hope you have gotten a pretty good idea about how the vaccines are developed and why do they take very long time. It makes us appreciate the researcher’s continuous efforts and patience.
Before finishing this article, just a quicky:
Q#3. Do you know how many years it took for polio vaccine to develop?
A#3: It was also more than 20 years.
Dr. Jonas Salk, was the first one to develop this vaccine successfully that was administered in 3-4 shots under the skin. He completed his work in 1955. After that Dr. Albert Sabin carried his legacy and created its most famous administered form in 1960 i.e. oral polio vaccine (OPV) which has been given to billions of the children as a part of polio eradication programme.