By Aiman Altaf
With the COVID-19 pandemic devastating the world, everybody has been awaiting a vaccine for some time. Recently, news outlets have been flooded with the progress of various vaccine manufacturers. To make getting information a little easier, we have summarized some key vaccine contenders, along with types of coronavirus vaccines and how they work in the body.
Types of Coronavirus Vaccines and How They Work
Coronavirus is caused by the SARS-CoV-2 virus. Vaccines generally work by exposing the body’s immune system to molecules from the target pathogen (in this case, the coronavirus), causing an immune response. There are four main types of coronavirus vaccines being developed:
Genetic vaccines: This type of vaccine is composed of the genetic material of the pathogen, and can be either mRNA (messenger RNA) or DNA depending on the virus. When this genetic material enters host (human) cells, it is “read” by the host cell causing antigens to be produced, which triggers an immune response. The challenge with this type of vaccine is getting the genetic material into human cells, which have a selectively permeable membrane. Some potential options include using nanoparticles to deliver it, or using a “gene gun” that propels the genetic material into skin cells. This is why genetic vaccines have not been used before and viral vector vaccines are more common.
The leading coronavirus vaccine candidates are mRNA based, carrying the genetic material that encodes the coronavirus spike protein. This protein is what the coronavirus displays on its surface and uses to invade body cells. When the mRNA from the vaccine enters body cells, it causes them to produce the spike protein and release it into the bloodstream. This isn’t enough to cause viral infection, but it is enough to cause the immune system to produce a response that includes producing specific antibodies and creating memory cells, which will help the immune system better tackle the virus if it ever encounters it. If companies like Moderna and Pfizer/BioNTech succeed in producing an mRNA vaccine, it will be the first to ever be in use. This is a great achievement because mRNA vaccines eliminate a lot of the manufacturing process and can quickly be mass-produced. Additionally, vaccines for various antigens could be manufactured by using a template and in the same facilities, reducing costs.
Viral Vector Vaccines: These vaccines are made of viruses that act as vectors by carrying the genetic material of the coronavirus. There are two main types: non-replicating vector vaccines can only produce the vaccine antigen, not other viral particles, while replicating vector vaccines can also create new viral particles in infected cells, which then infect other cells that will also make the viral particles.
The coronavirus vaccine candidates use manufactured adenoviruses (common viruses) that have most of their other genes removed, to deliver the coronavirus spike proteins into cells. These are non-replicating vector vaccines. The main difference between viral vector vaccines and genetic vaccines is that in the former, vaccines must deliver the genetic material through another virus which can make manufacturing it more complicated than it is for genetic vaccines. However, it is used more commonly because directly injecting genetic material does not cause it to enter host cells, while in a vector it can easily enter host cells.
Protein-Based Vaccines: Unlike the previous two vaccines, these vaccines either contain whole proteins from the virus, or segments of protein. These proteins act as a foreign material when they enter the human body and trigger an immune response. These are a subclass of subunit vaccines, which can include other components of bacteria or viruses other than proteins. Some vaccines can also be made of nanoparticles that are covered in many protein fragments. These vaccines are considered very safe because they are incapable of causing disease, while those involving genetic material can sometimes cause disease. However, because these vaccines must be biologically manufactured in yeast or bacteria they are more complicated, expensive, and time-consuming.
Inactivated or Live Attenuated Virus Vaccines: The virus is either killed with chemicals (inactivated) or weakened (attenuated) but kept alive, prompting an immune response without causing infection. Inactivated viruses contain the disease-causing virus or parts of it, but the genetic material is destroyed which is why they are considered to be safer. Live attenuated vaccines are just weakened forms of the real pathogen, so they produce the same immune response to a lower extent. This vaccine type cannot be administered to immunocompromised individuals or pregnant women, and is more dangerous overall, but highly effective. There are different ways of inactivating or attenuating viruses, depending on the individual virus, and these methods can be very costly and require stringent procedures.
For more information about what viruses are and how vaccines function, please visit Freeha Anjum’s article.
Vaccine Approval Process
Vaccines have to go through many stages of testing before they can be approved for mass production and administration. These stages are summarized as follows:
- Preclinical testing: the new vaccine is tested on cells (in vitro) and administered to animals to see if it causes an immune response
- Phase 1 Safety Trials: the vaccine is given to a small number of people to test how safe it is and its appropriate dosage
- Phase 2 Expanded Trials: the vaccine is given to hundreds of people from different population groups, like the children and senior citizens, to analyze the effect the vaccine has on different groups of people
- Phase 3 Efficacy Trials: the vaccine is administered to thousands of people, along with a group of people who receive a placebo. Then, the number of people who become infected are analyzed, to see the total percentage of infections and whether they come from the group that was vaccinated or given the placebo. Since this trial is done on such a large number of people, it is easier to find rare side effects that may not have been apparent in earlier trials. It is important to note that at this stage, efficacy, not effectiveness, is being tested. Efficacy describes the performance of the intervention in an ideal and controlled environment, whereas effectiveness can only be measured in the real world when the vaccine is administered at large.
- Early or Limited Approval: Some countries approve the vaccine before trials are complete, or approve it for a small subgroup of the population (e.g. healthcare workers). This has been done in China and Russia for coronavirus vaccines. However, doing so carries significant risks since the full effects of the vaccine are not known at this point.
- Approval: full approval occurs at the national level, where regulators review trial results, and have different criteria they use to evaluate the vaccine.
Leading Vaccine Contenders:
Moderna vaccine: In Stage 3 trials involving 30,000 American participants including high-risk and elderly individuals, this vaccine showed an efficacy of 94.5%. The fact that about 42% of participants were high risk and elderly individuals in this trial makes its results even more promising. Moderna will apply to the FDA for emergency use authorization in the upcoming weeks. This vaccine can be frozen for six months and refrigerated for up to 30 days after thawing. Moderna has said it hopes to manufacture 500 million to 1 billion doses by the end of 2021. No significant safety concerns were associated with this vaccine, and most reactions to the injection were mild to moderate and short-lived.
Pfizer-BioNTech: In Stage 3 trials which was the first American one to involve children as young as 12 years old, there was an efficacy of 95%. No serious side effects were associated with the vaccine. It has already been approved in the US, Canada, and UK, among other countries. This vaccine must be frozen to -70 degrees C until it’s ready to be injected, which makes storage and transportation much more complicated. The vaccine developers hope to manufacture 1.3 billion doses by the end of 2021.
Viral Vector Vaccines
AstraZeneca/Oxford: Results from phase 2/3 and phase 3 trials show an average efficacy of 70% with a potential efficacy of 90% with different dosing. However, results are questionable because they combine different trial groups that were given different dosages. AstraZeneca expects to manufacture 2 billion doses annually if approved.
CanSino Biologics: The Chinese military approved the vaccine for limited use on June 25 even before phase 2 trials had concluded. Phase 3 trials started in August.
Gamaleya Research Institute: This vaccine, called Sputnik V, launched a phase 3 trial based on which scientists estimate the vaccine has a 92% efficacy. The vaccine has been approved for early use in Russia.
Novavax, Medicago, and Anhui Zhifei Longcom have started phase 3 trials, with no significant results to report at this point.
Inactivated or Attenuated Virus Vaccines
Wuhan Institute of Biological Products/Sinopharm: The Chinese government gave Sinopharm approval to inject this vaccine and the next one, into government officials, health care workers, and other select groups. Sinopharm said that lamost a million people in China had received the vaccine. This vaccine is also approved for limited use on healthcare workers and government officials in UAE.
Beijing Institute of Biological Products/Sinopharm: This vaccine, also distributed by Sinopharm, is approved for use on government officials, healthcare workers, and other select groups in China . It is also approved for limited use in the UAE.
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Sanjay, Mishra. “Here’s How Pfizer’s And Moderna’s Breakthrough COVID-19 Vaccines Work.” ScienceAlert, 22 Nov. 2020, www.sciencealert.com/the-pfizer-and-moderna-vaccines-are-a-breakthrough-here-s-how-they-work.
“What Are Whole Virus Vaccines and How Could They Be Used against COVID-19?” Gavi, the Vaccine Alliance, www.gavi.org/vaccineswork/what-are-whole-virus-vaccines-and-how-could-they-be-used-against-covid-19.