In the past few months, we all have been exposed to rumour-mongering and negative skepticism floating over the news and social media. I have spent a decade in the field of Biomedical Engineering (B. Tech, M.S. and Ph.D.) and am currently working in the R&D division at Illumina, a world leader in developing genomic sequencers that played a paramount role in tracking COVID-19’s spread and mutations, and the production of mRNA-based vaccines.
I am a huge advocate for getting vaccinated as soon as possible. One of the biggest myths proving to be an obstacle to this is that COVID-19 vaccines might not be safe as they were rushed! Through this piece, I want to shed some light on the process of vaccination development.
What are vaccines?
The job of vaccines is to safely expose our body’s defence machinery (immune cells) to an antigen (protein from the infectious agent, such as SARS-CoV-2 virus). This will activate and prime our immune system to generate cells and antibodies that will fight-off and destroy the real pathogen when it actually enters our body. There are traditional ways of developing vaccines:
- Live-attenuated vaccine: use of a weakened form of the disease-causing pathogen
- Inactivated vaccine: use of the killed version of the disease-causing pathogen
- Subunit vaccine: use of a part/subunit of the disease-causing pathogen such as spike proteins
These conventional vaccines contain the antigen itself. The next-generation vaccines that is viral vector vaccines and genetic vaccines (such as mRNA vaccines) trigger our own cells to generate the antigens that in turn activates the immune system. Click here to watch a great video animation of different vaccine types.
The mRNA-based COVID-19 vaccines from Moderna and Pfizer were amongst the first ones to get approved in several countries around the globe. What is monumental about this vaccine technology is its design and efficacy.
India’s Council of Scientific and Industrial Research has committed to bringing mRNA vaccines to India. Genova Biopharma, based in Pune, is currently working on an mRNA COVID-19 vaccine.Tweet
How do mRNA vaccines work?
RNA is the genetic material of certain viruses including SARS-CoV-2 (that leads to COVID-19). In our body, the genetic material is DNA, and certain regions of the DNA get transcribed to messenger RNA or mRNA. This eventually guides the production of specific proteins. In common language, mRNA can be considered as the protein blueprint. The sequence of mRNA determines what protein is made.
mRNA vaccines have strands of mRNA that encode for spike protein. This protein will be unique to SARS-CoV-2. Spike protein is what enables the virus to hijack our cells. These strands can be synthesized artificially as long as the genetic sequence of the virus is known. These strands are encapsulated inside lipid nanoparticles that are injected into our bodies. The purpose of these nanoparticles is to safely deliver the mRNA to our cells.
Once delivered, the cell machinery (ribosomes) converts these mRNA strands into spike proteins (in this case, specific to SARS-CoV-2). At this stage, they will get expressed on our cell surface. In other words, mRNA vaccines trick our cells into using their protein-making machinery to create a viral antigen, thus bypassing the need for an actual virus particle (needed in traditional vaccine technologies).
Our immune system then responds to these proteins that lead to the activation of certain cells and antibodies that can recognize and fight off the viruses in case of an infection.
I have linked other research papers at the end of this article for anyone interested in further reading on mRNA vaccines.
What enabled record-breaking times for COVID vaccine development?
As we know from previous diseases/epidemics, vaccine development usually takes 5–10 years. In the past year multiple vaccines have been developed in a span of months. Therefore, it is natural to have some apprehension over their safety and effectiveness. Before jumping to conclusions, we need to consider some of the key advantages for vaccine developers in this pandemic:
- No time wasted in raising capital because of huge funding from both private and the public sector
- No time wasted in coordinating and performing phase trials for studies due to easy availability of thousands of subjects (typically, researchers have to wait many months and sometimes years to arrange trial volunteers)
- Since COVID-19 is highly contagious and widespread, it did not take long to see if the vaccine worked on the study volunteers
- High priority given by health regulatory bodies, such as FDA, to thoroughly review the safety studies and authorize emergency usage
- Recent advances in genomic sequencing led researchers to successfully uncover the viral sequence of SARS-CoV-2 in January 2020 — a couple of weeks after the initial reporting of cases in Wuhan, China
- Global collaborations allowed researchers and scientists to actively and efficiently share COVID-19 related data
- For years, researchers have already been working on related viruses, which cause SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome), and the knowledge gained there was useful for vaccine development for SARS-CoV-2
- Vaccine developers didn’t skip any testing phases; steps were conducted in just as deliberate and careful a manner on overlapping schedules to gather data faster
- Pharmaceutical companies kick-started mass production of vaccines immediately after testing concluded while waiting for the final approval from the FDA
How much time did it actually take for mRNA vaccine development?
I have had numerous opportunities in the last few months to attend private seminars and have fireside chats with industry & academic leaders (thanks to Illumina!) such as Stephane Bancel (CEO Moderna), Scott Gottlieb (former US FDA Commissioner/Director), and Frances Arnold (Nobel Laureate, 2020). These enriching conversations have shown me that the clinical trials for the vaccine were thorough and meticulous.
Even though this is the first time mRNA vaccines have been approved by the FDA, the concept of mRNA vaccines is not new. They were first reported to be effective for direct gene transfer for the first time in 1990. However, they weren’t utilized initially because of the poor stability since enzymes, called ribonucleases, present in our body would attack and chop up these foreign mRNA strands. The scale of production of these vaccines was also limited which further deterred their use. Decades of research has gone into enabling the successful delivery of mRNA which can effectively elicit a robust and durable immunity.
Dedicated scientists have streamlined the process of introducing mRNA in our cells. Development of the mRNA vaccine can now be carried out in significantly lesser time compared to traditional methods since mRNA bypasses the need of virus particles or production of viral proteins/antigens.
All that is needed to develop an mRNA vaccine is the genetic sequence of the related virus. This turns out to be a great advantage, especially when encountered with a completely new viral strain. For SARS-CoV-2, it took less than a month for Moderna to have a vaccine candidate ready for trials once the genomic sequence of the virus was published!
What are the benefits of mRNA vaccines over other types?
mRNA vaccine technology uses a non-infectious element and can be developed in a laboratory using a DNA template and readily available materials. It doesn’t even need a sample of the virus; all that’s needed is the genome sequence of the pathogen. This means the process can be standardized and scaled-up, making vaccine development faster than traditional methods. Furthermore, RNA simplifies the manufacturing a lot. The same facility can be used to make RNA for different diseases.
The Moderna vaccine can be stored at regular freezer temperatures (-20 degree Celsius) for 6 months and for 30 days after thawing in a common fridge. It can also remain in room temperature for 12 hours. Pfizer can be safely stored at -70 degree Celsius but cannot be opened often. Once thawed, it can remain refrigerated for up to 5 days.
On April 13th, the Indian government opened doors to vaccines that have been globally approved by the US, EU, UK, Japan, and the World Health Organization. Tata Medical and Diagnostics and the Council of Scientific and Industrial Research are keen on bringing the Moderna vaccine to India. Pfizer, which had previously applied to commence roll-out in the country, has announced its commitment to make the vaccine available in the immunisation drive.
I have linked additional resources related to vaccine development at the end of this article.
Can external mRNA modify or alter our own genetic material?
No! The mRNA strand never enters the cell’s nucleus or interacts with our DNA. After the piece of the spike protein is made, the mRNA strand gets broken down by our cell’s enzymes and disposed from our body.
Do COVID vaccines have severe side effects?
The COVID-19 vaccine can have short term side effects, such as body aches, headaches, soreness, chills, fever, muscle pain, lethargy, and nausea, lasting for a few days. These are signs that the vaccine is working to stimulate your immune system. The first dose triggers the innate immunity, which activates the adaptive immunity in 1–3 weeks. After getting the second dose, both innate and adaptive immune systems get triggered that can lead to harsher side-effects.
People who have a history of allergies should consult their doctor prior to getting vaccinated.
Do you need a vaccine if you’ve already had COVID-19?
It is recommended to get the COVID-19 vaccine, even if you’ve had COVID-19 previously. There is not enough information currently available to conclude how long someone is protected from getting sick again after recovering from COVID-19. After getting infected from SARS-CoV-2, the person gains natural immunity, which varies from person to person. Some early evidence suggests natural immunity may not last very long. Vaccination triggers adaptive immunity that has a long-lasting effect, and this is something that experts are trying to learn more about.
Can the COVID-19 vaccine affect pregnancy?
- The Challenges of Vaccine Development against a New Virus during a Pandemic
- Safety and Immunogenicity of the Vaccine in Older Adults
- Conversations with Dr. Howard Bauchner, MD, Editor-in-chief, Journal of American Medical Association
- mRNA Vaccine Era
- mRNA against COVID-19: Preliminary Report
- mRNA Vaccine Delivery
- mRNA Vaccines – a new era in vaccinology
- Developing mRNA-vaccine technologies
- Advances in mRNA vaccines for infectious diseases
Even if you get vaccinated, please make sure to continue maintaining social distancing and wearing masks. The new variants (such as B.1.1.7 and B.1.135) are rapidly spreading and researchers and scientists do not have enough data to conclude if the current vaccines will be as effective against these new variants.