- 20 Jan 2021
Moderna was the second company to release promising preliminary data on a COVID-19 vaccine after Pfizer, in collaboration with BioNTech, reported that its vaccine was more than 90 percent effective in early results. To add to the spices, U.K.-based pharmaceutical company AstraZeneca has developed a vaccine with the University of Oxford, that showed an average efficacy of 70% in preventing COVID-19, according to the company. Which among these fares better?
It seems the world breathed a collective sigh of relief when Pfizer / BioNTech and Moderna recently reported the first efficacy analyses of their Covid-19 vaccines. The brilliant results have already come as a surprise to the developers of the vaccine who expected effectiveness calculations to be ranging somewhere around 75% instead of the established 90%. Pfizer released initial data on its vaccine developed with German partner BioNTech SE that showed it to be more than 90% effective. On the other hand, rival Moderna claims 94.5% effectiveness on its production. However, the recent declaration of AstraZeneca has raised the bars for an efficient and well-structured vaccine.
What are mRNA vaccines?
Earlier the key component of vaccines used to be antigens(segments of the disease-causing organism), stabilizers, adjuvants, antibiotics, and preservatives. However, over the last decade improved knowledge of immune protection and a big leap in genetic engineering has allowed the induction of a variety of new types of vaccines through the manipulation of DNA, RNA, proteins, and sugars. Among these mrna vaccines evoke a new era in the history of vaccine development.
Image Credits: ScienceDirect
mRNA vaccines work through mRNA translation. mRNA(messenger RNAs) are entrusted with the work of encoding genes which produce proteins in our body. Same is the case for coronaviruses. The spike protein which assists them in attaching themselves to the human body is produced by a certain kind of mRNA. These mRNAs have been identified by the researchers and doctors, thus providing for the modern vaccines.
In mRNA vaccines, a patient is inoculated with a small piece of this gene material which thereafter translates into the same protein body that is used by the coronaviruses to attack their hosts. The patient's cells will then produce the virus proteins and their antibodies simultaneously. This way of inducing an immune response does not demand a direct handshake between the antigen presenting cell (namely the virus itself in most of the cases) and a specific type of cell which in turn reduces the possibility of people falling sick post vaccination.
On the other hand, Astra Zeneca’s vaccine candidate is a nonreplicating, weakened version of the common cold virus that contains the SARS-CoV-2 spike protein. This approach has been successful before as the first Ebola vaccine. Covaxin, however, uses the traditional methods of developing vaccines which undoubtedly have their own advantages.
Where does Moderna lead over Pfizer?
While Pfizer seems to be on track to be the first vaccine maker to get FDA authorization for a drug that can reduce the spread of COVID-19, there seems to be one crucial problem with the particular vaccine. It requires South Pole temperatures for storage and transport, making distribution incredibly challenging. These vaccines must be stored and transported at minus 70 degrees Celsius, which translates to minus 94 Fahrenheit. Shipping and storing the vaccine will be a huge issue that public health authorities must overcome to get the vaccine to all corners of the world. Pfizer plans to have 100,000 coolers ready by the end of the month and double that figure by March.
Dry ice inside those boxes will keep the vaccine cool. They’ll also be equipped with sensors that will allow Pfizer employees to monitor locations and temperatures as FedEx and UPS handle deliveries.
Hospitals and pharmacies will need to find ways to store the doses until they’re needed and that's where Moderna gets a boost. Moderna chief says that their vaccines can be stored in a regular fridge at minus 20 degrees Celsius for 2-3 days, quite like insulin. Transportation and storage are just like any other vaccine. The icing on the cake is the additional diluent that comes with the vaccine. This removes the need for on-site dilution of the vaccine, thereby making it easier for the mass population to get quick dosages.
What are DNA vaccines?
Genetic/ DNA immunization is a novel technique used to efficiently stimulate humoral and cellular immune responses to protein antigens. This method has currently been employed by AstraZeneca to develop its vaccine against Covid-19.
Image Credits: biology.kenyon.edu
Scientists at AstraZeneca have deployed a Chimpanzee adenovirus as the key component of the vaccine. It's unlikely that humans would develop an immune response against these viruses since they haven't been much exposed among the human population, thus making it a safe choice.
Adenoviruses are common viruses belonging to the family Adenoviridae and causing a range of illnesses including common cold, flu etc. Now, there happens to be a portion in the middle of these adenoviruses that causes them to undergo replication. Genetic engineers at AstraZeneca have successfully deleted the specific portion, only to replace it with a genetically designed code. As a result, the viruses will be unable to replicate and therefore won't be a potential threat to the human population. The double-stranded DNA will enter the cytoplasm and nucleus of human cells but will not be incorporated into the host genome, according to the claims made by AstraZeneca. Instead, the DNA will get transcribed into RNA (mRNA to be more specific) and thereafter carry on it's function like mRNA vaccines.
How does AstraZeneca become the game changer?
Image Credits: BBC
The lower efficacy rates for the AstraZeneca vaccine may look pallid or seem like an encumbrance on the surface, but in reality the U.K. vaccine is blessed with quite a few advantages over the other two.
• There appears a crucial difference between the human trials carried out by Pfizer or Moderna and AstraZeneca. AstraZeneca tested its vaccine in two phases-initially 9000 volunteers were booked in Brazil and thereafter 3000 from the U.K. While Pfizer and Moderna waited for the subjects to become symptomatic with the symptoms of Covid-19 and their efficacy results were calculated accordingly. However, AstraZeneca did it differently. They were constantly doing nasal swabs and other necessary tests to check for infections. Professor Roger Seheult, MD says,"While we are certain, if what they say is true, that these two vaccines are effective in preventing symptoms, in preventing diseases that take you to the hospital..we do not know if they can curb the spread of infections which we are almost certain in the case of AstraZeneca"
• Unlike the Moderna and Pfizer-BioNTech vaccines, which must be stored/transported at negative 20-80 degrees Celsius, the Oxford-AZ candidate can be stored up closer to normal fridge temperatures, which means it can be distributed and administered cheaper and faster to people.
• As a gesture of moral probity in these tough times, AstraZeneca has promised that it will not make any profit during the pandemic from the vaccine. It has reached agreements with governments and international health organisations such as Gavi that pegs its cost at about $2.50-$3 a dose.
• Scientists came about an interesting observation in the Brazilian portion of human trials. Subjects were injected with two full doses of the vaccine with a gap of 28 days in between the two and the efficacy rate was calculated to be 62%. In the U.K., they injected the subjects with half a dose in the first shot and another full dose, 28 days later. Surprisingly, due to some kind of surreptitious error, this one was around 90% effective
While the reasons for this are still being examined, the half dose giving higher protection is really good news — as the manufacturers will have more doses available to vaccinate people, thereby making it possible to cover more of the population, especially in the initial months when supply will be constrained.
All these facts inevitably confirm to the words of Dr Stephen Griffin, from the University of Leeds, that the vaccine has great potential to be delivered across the globe, achieving huge public health benefits.
Indigenous Covaxin enters phase 3 trials and why is it the safe choice?
Although the AstraZeneca vaccine is being produced in India, and could be first to reach Indians, nothing can be better than a self-starter. Phase three trials of India’s first vaccine against COVID-19 have started in what is the largest human trial to be conducted with about 26,000 participants. The news comes a day after the US biotech firm Moderna Inc said preliminary data from a continuing phase three study of its experimental COVID-19 vaccine showed it to be 94.5 percent effective.
“The vaccine has shown good efficacy,” senior ICMR scientist Rajni Kant, who is also a member of its COVID-19 task force, said at the research body’s New Delhi headquarters. “It is expected that by the beginning of next year, February or March, something would be available.”
"The arrangement of cold-chains for storing the vaccine developed by Pfizer at a low temperature of minus 70 degrees Celsius is a big challenge and it will not be easy for any nation. But then, if at all it has to be obtained, we are examining what we need to do...and will work out a strategy," said NITI Aayog member (Health) Dr VK Paul, who also heads the National Task Force on COVID-19. He also added that sufficient doses of the vaccine, as is required by Indian population, will probably not be possible. Nevertheless, the government is keeping no stone unturned and is looking at all possibilities and will work out a strategy for its procurement and distribution in case it gets the regulatory approvals.
Image Credits: Bharat Biotech
A fundamental problem in mRNA vaccines is that the mRNAs degrade relatively rapidly after they have produced the proteins. These vaccines generally remain active for about a couple of months, after which one needs to get revaccinated. Adding to that, mRNA vaccines are comparatively new in the domain. Most current research into RNA vaccines is for cancer. There is still a lot of work to be done before mRNA vaccines can become standard treatments, in the meantime, we need a better understanding of their potential side effects, and more evidence of their long term efficacy.
Another potential challenge delivering the vaccine effectively to cells is challenging since free RNA in the body is quickly broken down. To help achieve delivery, the RNA strand is usually incorporated into a larger molecule to help stabilise it and/or packaged into particles or liposomes. With so many uncertainties in line, Covaxin may just be a slightly safer option to consider as of now.
Let that sink in. Owing to the accelerated pace of the vaccine trials, we are only able to judge how the vaccine activates the body’s primary immune response and this is true, even for AstraZeneca. This initial response may raise antibodies that can protect against infection, but that protection will fade and may fade rapidly, in as short a period as two months. Most vaccines rely on a long-term memory response instead. This long-term immune response is best tested six months to a year after vaccination which means, in the case of accelerated vaccine approval, we do not know if the vaccines generate long-term memory. Furthermore, we aren't even aware of the long-term side-effects if any.
In the hyper-connected world that we live in today, nobody is safe until everybody is safe. No matter how much alluring the promises sound, unless we can reach out to every nook and corner of the world, we are still in danger and the risk of contracting the disease remains.
Yet, it is inevitable that scientists and researchers are trying their best to weather the storm caused by the dreadful pandemic and we too long for that one solution which will be an end to all the miseries.