On January 16, India launched the world’s largest COVID-19 vaccine drive to vaccinate 1.3 billion people. Shots of Covishield and Covaxin vaccines were administered to frontline healthcare workers at medical centers across the country. Vaccinations are going on in other countries as well. In the US, people are taking shots of vaccines by Moderna and Pfizer. In this article, we will try to understand the science behind COVID-19 vaccines and careers in vaccine research. We will particularly focus on Covaxin vs Covishield vs Sputnik V – the science behind the Covid-19 vaccines and their differences with the vaccines manufactured by Moderna and Pfizer.
Basics of Vaccines
To prevent or cure any disease, you need either a therapeutic agent (e.g. drug) or a preventive one (e.g. vaccine). Therapeutic interventions don’t just spring out of thin air. Creating one, whether it be a therapeutic meant to treat disease or a vaccine meant to prevent it, is a fascinating process that begins with a thorough examination of the biological foe in question.
Active and Passive Immunization
The immune response towards any infection can be passive or active. Passive immunization is when antibodies are directly transferred from one individual to another. Such passively transferred antibodies accord immediate protection – but it wanes gradually and the individual eventually becomes susceptible to the disease again. It could be natural or artificial.
The placental transfer of antibodies from the mother to the fetus gives natural passive immunity. Convalescent plasma therapy, involving the transfer of plasma containing specific antibodies from recovered individuals to susceptible individuals, provides passive immunity as well.
Vaccines provide active immunization: they deliberately introduce a foreign substance, called an antigen, into the body to induce the body to mount an immune response. Though the protection is not conferred immediately, the immunity lasts for a considerably longer period once established. Repeated doses of the same antigen could boost immunity further.
How Do Vaccines Work?
A vaccine works like a virus and initiates an immune response – but without causing major illness.
The basic role of a vaccine is to induce an immune response, which will then offer protection against a pathogen by forcing your body to create antibodies that attack antigens, the components of a pathogen that produce the immune response. So when the actual virus comes knocking, your body already recognizes the intruder and can deploy its antibody arsenal.
Many common vaccines contain little bits of the virus or bacteria itself that either has been killed after being grown in a lab or are live but greatly weakened and are therefore unlikely to get you sick.
When an antigen enters the body, cells called dendritic cells to get attracted to it, and then carry the antigen to T lymphocytes. The T lymphocytes identify these antigens and bind to them.
When the body is exposed to the same antigen again, the circulating antibodies bind to the antigen. This is what they mean when they say the immune system becomes familiar with the antigen, and the immune response the second time is even more effective.
This memory is known as immunological memory, and it forms the basis of vaccination.
Types of Vaccines
Ideally, a vaccine should trigger an adequate immune response without harming the body. There are different types of vaccines to achieve this outcome. Conventional vaccines fall into two broad categories: live attenuated vaccines and inactivated killed vaccines.
Actually, there are 4 main types of vaccines:
- Live-attenuated vaccines
- Inactivated vaccines
- Subunit, recombinant, polysaccharide, and conjugate vaccines (e.g. Hepatitis B, HPV)
- Toxoid vaccines (e.g. Diptheria, Tetanus)
- DNA Vaccines
- mRNA Vaccines
- Recombinant vector vaccines
Live Attenuated Vaccines
Live attenuated vaccines contain whole virus particles. Inducing the virus to replicate under unnatural conditions reduces its virulence. For example, researchers could have injected the virus into an ‘unnatural’ host, causing the virus to eventually lose its adaptation towards the actual host, and transform to a less virulent form. That is, it can no longer cause disease as well as it could before. This process is called attenuation.
The level of attenuation is critical to a vaccine’s success. Over-attenuation could render the vaccine ineffective, while under-attenuation could cause the vaccine itself to produce disease.
The chickenpox, measles, totavirus, mumps and rubella vaccines are all live vaccines.
Inactivated vaccines contain a part of the virus instead of the whole. During preparation, researchers remove those parts of the virus required for viral replication, making these vaccines safer than the live attenuated type.
On the flip side, inactivated vaccines, in general, don’t accord long-lasting protection, like live vaccines. Sometimes, a substance called an adjuvant is added to inactivated vaccines to boost the immune response and make them last considerably longer. However, including an adjuvant increases their overall cost.
Hepatitis-A, polio, rabies, flu vaccines are inactivated vaccines.
Vaccines are the world’s best hope of ending a pandemic that has claimed more than 1.7 million lives globally. More than 60 COVID-19 vaccine candidates are currently undergoing human trials, according to the World Health Organization.
The SARS-CoV-2 virus (COVID-19) is studded with proteins that it uses to enter human cells. These so-called spike proteins make a tempting target for potential vaccines and treatments. When you see the pictures of the virus that has the colored spike protein, that red bit that’s protruding off that cylindrical virus compound.
In the case of the coronavirus, identifying the “weak spot” was the crucial first step. It’s something rather sinisterly named the spike protein.
That “spike protein” does exactly what you’d think a spiked object would do: It pierces something else. The spike protein attaches to the ACE2 protein present in human cells. And so we know that’s how this virus actually infects people.
Pfizer and Moderna Vaccines (mRNA Vaccines)
The vaccine contains material from the virus that causes COVID-19 that gives our cells instructions for how to make a harmless protein that is unique to the virus. After our cells make copies of the protein, they destroy the genetic material from the vaccine. Our bodies recognize that the protein should not be there and build T-lymphocytes and B-lymphocytes that will remember how to fight the virus that causes COVID-19 if we are infected in the future.
Vaccines made by Pfizer/BioNTech and Moderna have already been authorized for use in some countries, including the United States. Late-stage clinical trials showed both vaccines appeared to be at least 94% effective. Until the UK approved the Pfizer/BioNTech vaccine in December last year, no RNA vaccine had ever received authorization for general use.
Both the Pfizer and Moderna vaccines will contain a piece of the genetic coding for the coronavirus’ spike protein, which officials say has been separated from the virus, synthetically produced, and wrapped in a lipid nanoparticle — a type of molecular envelope.
When the lipid-wrapped mRNA enters our cells it stimulates them to produce their own spike protein. These new spike proteins will be recognized by our immune cells, which and create antibodies that latch onto them.
When a person is exposed to COVID-19, the body recognizes the virus’ spike proteins of the same shape. From there, the immune system produces the same antibodies that prevent the individual from getting sick. Even if a person is infected, those antibodies prevent the virus from replicating so severe illness can be avoided.
Messenger RNA (aka mRNA) is a powerful biological tool. It’s the molecule that actually instructs your cells what to make, such as proteins.
It means you could harness mRNA to turn your body’s cells into mini drug-making factories that can fight various diseases. As little as a year ago, large swaths of the biotech community were skeptical of using mRNA technology to make treatments.
Advantages & Disadvantages of mRNA Vaccines
Unlike traditional vaccines, you don’t have to spend months upon months manually harvesting and purifying a pathogen’s antigens in order to make the final product. You can simply let the instruction-carrying mRNA sequences loose into the body. After that, the body’s cells do that heavy lifting all by themselves.
For Pfizer, one of the more complex issues is the ultracold temperature its COVID vaccine requires for storage, about -70 degrees Celsius. That’s because of the mRNA component of its specific vaccine, which could fall apart without being thoroughly frozen.
So while mRNA vaccines present some problems, the quickness they provide is exactly what’s needed at this moment.
The Oxford/AstraZeneca COVID-19 vaccine employs a more established technique called the viral vector. The vaccine uses a bioengineered version of a harmless common-cold virus found in chimpanzees to instruct human cells to make antigens.
The vaccine contains a weakened version of a live virus—a different virus than the one that causes COVID-19—that has genetic material from the virus that causes COVID-19 inserted in it (this is called a viral vector).
Despite some uncertainty over trial results, the UK authorized the vaccine for emergency use in December, and India authorized a version of the vaccine called Covishield on Jan 3, 2021. Serum Institute of India (SII) is the manufacturing partner of AstraZeneca. According to Adar Poonawalla, Chief Executive Officer, SII, the vaccine would be 90 to 95% effective if the two shots are parted by around 2-3 months.
The Oxford-AstraZeneca vaccine is based on the virus’s genetic instructions for building the spike protein. But unlike the Pfizer and Moderna vaccines, which store the instructions in single-stranded RNA, the Oxford vaccine uses double-stranded DNA.
The researchers added the gene for the coronavirus spike protein to another virus called an adenovirus. Adenoviruses are common viruses that typically cause colds or flu-like symptoms. The Oxford-AstraZeneca team used a modified version of a chimpanzee adenovirus, known as ChAdOx1. It can enter cells, but it can’t replicate inside them.
The Oxford-AstraZeneca vaccine for Covid-19 is more rugged than the mRNA vaccines from Pfizer and Moderna. DNA is not as fragile as RNA, and the adenovirus’s tough protein coat helps protect the genetic material inside. As a result, the Oxford vaccine doesn’t have to stay frozen. The vaccine is expected to last for at least six months when refrigerated at 38–46°F (2–8°C).
After the vaccine is injected into a person’s arm, the adenoviruses bump into cells and latch onto proteins on their surface. The cell engulfs the virus in a bubble and pulls it inside. Once inside, the adenovirus escapes from the bubble and travels to the nucleus, the chamber where the cell’s DNA is stored.
The adenovirus pushes its DNA into the nucleus. The adenovirus is engineered so it can’t make copies of itself, but the gene for the coronavirus spike protein can be read by the cell and copied into a molecule called messenger RNA, or mRNA.
The mRNA leaves the nucleus, and the cell’s molecules read its sequence and begin assembling spike proteins.
Some of the spike proteins produced by the cell form spikes that migrate to its surface and stick out their tips. The vaccinated cells also break up some of the proteins into fragments, which they present on their surface. These protruding spikes and spike protein fragments can then be recognized by the immune system.
The adenovirus also provokes the immune system by switching on the cell’s alarm systems. The cell sends out warning signals to activate immune cells nearby. By raising this alarm, the Oxford-AstraZeneca vaccine causes the immune system to react more strongly to the spike proteins.
Covaxin is an inactivated COVID-19 vaccine candidate that will use adjuvant Alhydroxiquim-II to boost immune response and longer-lasting immunity. The SARS-CoV-2 virus strain was isolated from an asymptomatic COVID-19 patient at the National Institute of Virology (NIV) an Indian virology research institute.
Covaxin has been developed by Indian biotechnology company Bharat Biotech and clinical research body Indian Council of Medical Research (ICMR).
It is one of the oldest methods for vaccinating people – which means that whole, inactivated viruses are injected in the body to trigger an immune response. These whole batches of coronavirus must be grown, “killed” using a chemical or heat, and then made into a vaccine, making it a longer process, the report says.
The vaccine candidate was developed by BBIL in collaboration with the National Institute of Virology (NIV). NIV isolated a strain of the novel coronavirus from an asymptomatic Covid-19 patient and transferred it to BBIL early in May. The firm then used it to work on developing an “inactivated” vaccine — a vaccine that uses the dead virus — at its high-containment facility in Hyderabad.
Russia’s Sputnik V has been deemed to be safe and works in a way similar to the Oxford-AstraZeneca (Covishield) vaccine. Sputnik V’s approval came as India overtook Brazil to become the country with the second-highest number of cases globally.
It is a combination of two different adenoviruses (Ad26 and Ad5). The adenoviruses — viruses that cause common cold — are combined with the SARS-CoV-2 (the virus that causes Covid-19) spike protein, which prompts the body to make an immune response to it, according to The BMJ paper cited above. Using the same adenovirus for the two doses could lead to the body developing an immune response against the vector and destroying it when the second dose is administered. Two different vectors reduce the chance of this, it said.
It can be stored at temperatures of between 2 and 8C degrees (a standard fridge is roughly 3-5C degrees) making it easier to transport and store.
Unlike other similar vaccines, the Sputnik jab uses two slightly different versions of the vaccine for the first and the second dose – given 21 days apart.
They both target the coronavirus’s distinctive “spike”, but use different vectors – the neutralized virus that carries the spike to the body. The idea is that using two different formulas boosts the immune system even more than using the same version twice – and may give longer-lasting protection.
Hyderabad-based pharmaceutical major Dr Reddy’s Laboratories will be importing the first batch of 125 million doses to India. Supplies will be ramped up only next quarter when six Indian firms begin making the vaccine under the supervision of Dr Reddy’s.
New Strains of Coronavirus (Viral Mutations)
Viruses mutate because they’re constantly making copies of themselves in enormous numbers. To accomplish this, they have to hijack the hardware of a host cell that they infect. However, this process can be a bit sloppy.
Within a human body, a virus can replicate itself millions or billions of times, Hodcroft explains. If you were writing a draft of something millions of times on a computer, extremely quickly, you’d probably make some typos. That’s what’s happening with the viruses. “They make a typo” in their genetic code, she says. One letter of their ribonucleic acid (RNA) chain is replaced with another.
Viruses that use RNA as their genetic material, like SARS-CoV-2, are particularly vulnerable to mutations since the RNA molecule itself is more unstable than DNA. The process of copying RNA is also more prone to error.
These typos can be very useful for scientists because they happen at a regular rate, and are passed down through generations of the virus as it spreads through a community. Often, scientists can use these subtle changes to trace certain strains’ lineage and their spread through a population.
The majority of these typos are inconsequential when it comes to human health. One typo, or even a few typos, doesn’t usually change how the virus works. Some even harm the virus. According to scientists, people are much more likely to break it than to make it better when it comes to mutations.
The good news is that we already know how to respond to these new variants: in the same way we’ve been responding to the pandemic overall. The virus still transmits primarily through viral-laden breaths in the air. Mask-wearing, social distancing, and good indoor ventilation are as critical as ever.
Careers in Vaccine Research
COVID-19 pandemic is definitely not the last one our planet will experience. There would be more deadly pandemics in the future. Hence, we will need more skilled and trained personnel around.
Why Anti-Viral Drug Discovery Research is Challenging?
Another reason for huge career opportunities in vaccine research is that drug discovery & development against a virus is extremely challenging.
Unlike bacterial infections, viral diseases are a rather different matter. It’s primarily because of the unique, parasitical qualities of the virus, making drugs to treat infections ranging from the common cold to flu and Ebola has proven a much more daunting task, with a few major successes and many failures.
Bacteria are complete, free-living cellular organisms, equipped with the biology to survive and reproduce independent of the host they invade. As such, they offer up a variety of relatively easy targets for drug weaponry, though inappropriate use of antibiotics has led to a dire resistance problem.
Viruses essentially consist of nucleic acid — genetic material — encased in protein. A virus is chemically inert.
Only when they infiltrate a host, like humans, and glom onto a cell do viruses become active, burrowing into the cell and using its molecular machinery to replicate, creating more viruses to infect other cells.
That’s a difficult, more limited target, and drug developers have to ensure their medicine does not prove toxic to the host cell, as well as the virus attached to it.
Another reason that makes viruses harder to target with drugs than bacteria: their tendency to mutate more often and quickly, rendering any medicine targeting them less potent.
How to Get into Vaccine Research Careers
You can pick any undergraduate degree in biological or biomedical sciences if they wish to get into the world of vaccine development. Here are the popular options after 12th:
- Biomedical science
- Molecular & Cell Biology
- Pharmacy & Pharmaceutical Sciences
A Masters (MSc or MS) and Ph.D. are must for a career in vaccine research. You can choose to do Masters from India or abroad. Here are the ideal options at Masters level:
- Infectious Diseases
- Biomedical Sciences
Related Article: Careers in Infectious Diseases | Q&A with Dr. Sonia Punj
Jobs and Salaries in Vaccine Research
Vaccine Development research is usually expensive research and is funded by either universities or big pharmaceutical companies. The jobs, as such, hence would be available with university, industry, government, and not-for-profit organization laboratories.
Within the research domain, one usually starts at the Assistant Researcher level and works his/her way up the ladder to become a scientist and then a senior scientist. People with years of experience end up running their own independent research work which is funded by either of the above organizations.
Related Article: Top 10 Research Institutes for Biological Sciences in India
The average salary could range from anywhere between INR 35,000 per month to about INR 1 Lac per month – depending on the field you get into. A Microbiologist or a scientist involved in research work in the field of infectious diseases usually earns about 50,000 per month average salary. These can go up depending on the grade of the Scientist the job is on offer.
In foreign countries, salaries are pretty attractive. However, a research career path in biosciences is always challenging. So, don’t get into this stream only for lucrative salaries.
Vaccine research offers scientists the opportunity to work on a project that could directly impact public health, whether it is working directly at the lab bench, on a production line, or to support a clinical trial. You need to have the passion, perseverance, and burning determination of working on projects that have the potential to prevent or cure diseases.