COVID-19 vaccine: Progress and Challenges
As people adjust to life within the pandemic, they seem to have started accepting the fact that things like social distancing, working or studying from home and wearing face masks in public are going to be the way of life for the foreseeable future. Despite this, we cannot help but wonder when things would go back to normal and when we would be able to walk out of our houses without worrying about the risk of catching the virus. In the current scenario, a vaccine for COVID-19 seems like the only hope to lower down the number of newly emerging cases and getting things even remotely close to normal. As a result, the scientific community is pushing hard to develop a vaccine that can effectively prevent COVID-19. According to the World Health Organisation (WHO), more than 155 vaccines are currently under development, more than 23 of which are undergoing clinical trials 1.
What is a vaccine and how does it work?
A vaccine is a biological preparation that, when administered to an organism, works by training their immune system to fight a viral or bacterial infection that the vaccine aims to target. Vaccines are usually prepared using inactivated or weakened parts of the disease-causing organism like a surface protein or a toxin. Since these parts are inactivated or weakened, their introduction inside the body does not cause a full-blown immune reaction leading to the disease. 2 However, recently, new types of vaccines have been in development which use the genetic material of the disease-causing organisms, like DNA, to produce an immune response. 3 The aim of using vaccines is to stimulate the body's immune system just enough to generate antibodies or an alternative immune response against the introduced protein. This provides a quicker immune response in case of any subsequent infections by the infectious organism in the future.2
Stages of vaccine testing
After a vaccine is developed, it needs to be tested in preclinical and human clinical trials so that the safety and effectivity of the vaccine can be determined. Below are the stages of the vaccine testing process in the order in which they are carried out.
| Stage | Description |
|---|---|
| Preclinical trials | The vaccine candidate is tested for safety and ability to produce an immune response in animals. The animals used for testing are usually monkeys or mice. |
| Phase I trials | This trial is carried out in a limited number of human volunteers (usually less than 100). This phase aims to test the safety of the vaccine in humans and the ability to induce an immune response. Researchers also look out for any side effects. |
| Phase II trials | These trials recruit several hundreds of volunteers. The trial compares the volunteers who did and did not receive the vaccine. Determining a safe amount of dosage also takes place in this phase. |
| Phase III trials | This phase involves thousands of volunteers. This phase tests the efficiency of the immune response in preventing infection. The company also works on final specifications like storage of the vaccine, distribution, determining how long the vaccine can be used before expiring, etc. This is the final stage before licensing. |
| Phase IV | After the vaccine is released in the market and distributed, it is constantly monitored to see if it causes any side effects that weren't previously noted during the clinical trials. |
It is important to note that each stage of the clinical trial takes years to be completed. But with the pace at which the pandemic is progressing, it has become extremely important to have a vaccine out as soon as possible. As a result, many companies have decided to combine some phases of the clinical trials to accelerate the process. So, if a vaccine is in a combined phase I/II trial, it would be tested to meet the aims of both these phases in hundreds of volunteers. Once the clinical trials are completed, the vaccine needs to be approved by regulating authorities. This is done after reviewing the results from clinical trials.5
What COVID-19 vaccines are currently in development?
Several types of vaccines are being developed and tested to provide immunity against coronavirus (SARS-CoV-2). Many of these vaccines have performed wonderfully in preclinical trials and have moved on to further phases. Below are some of the top-performing COVID-19 vaccine candidates segregated based on the type of vaccine.
1. Whole-virus vaccine
Whole-virus vaccines contain inactivated or weakened form of the whole virus. The immune system recognizes the viral proteins and makes antibodies against them 6. Some examples of whole-virus vaccines being developed for COVID-19 are:
CoronaVac by Sinovac: A Chinese company called Sinovac conducted phase I/II trials for their vaccine called CoronaVac, which is an inactivated coronavirus vaccine. The results from initial trial gave positive results and the vaccine is now in phase III trials in Brazil, Indonesia and Turkey.7
BBIBP-CorV by Sinopharm: This is another inactivated coronavirus vaccine developed by a Chinese company called Sinopharm. The vaccine has shown promising results in phase I/II trials and is now in phase III trials in the United Arab Emirates, Peru, Morocco and Argentina.8
2. Viral vector vaccine
Viral vector vaccines use a harmless virus to deliver the genetic material of the disease-causing virus into the body. The genetic material codes for a protein of the disease-causing virus. The body then produces this protein and the immune system recognizes it and makes antibodies against it.9 Some examples of viral vector vaccines being developed for COVID-19 are:
ChAdOx1 nCoV-19 by University of Oxford and AstraZeneca: This vaccine uses a chimpanzee adenovirus to deliver the genetic material of SARS-CoV-2 into the body. The genetic material codes for the spike protein of the virus. The vaccine has shown promising results in phase I/II trials and is now in phase III trials in the UK, Brazil, South Africa and the US.10
Ad26.COV2.S by Johnson & Johnson: This vaccine uses a human adenovirus to deliver the genetic material of SARS-CoV-2 into the body. The genetic material codes for the spike protein of the virus. The vaccine has shown promising results in phase I/II trials and is now in phase III trials in the US, Brazil, South Africa and other countries.11
3. Nucleic acid vaccine
Nucleic acid vaccines use the genetic material (DNA or RNA) of the disease-causing virus to produce an immune response. The genetic material codes for a protein of the disease-causing virus. The body then produces this protein and the immune system recognizes it and makes antibodies against it.12 Some examples of nucleic acid vaccines being developed for COVID-19 are:
mRNA-1273 by Moderna: This vaccine uses messenger RNA (mRNA) that codes for the spike protein of SARS-CoV-2. The vaccine has shown promising results in phase I/II trials and is now in phase III trials in the US.13
BNT162b2 by Pfizer and BioNTech: This vaccine also uses mRNA that codes for the spike protein of SARS-CoV-2. The vaccine has shown promising results in phase I/II trials and is now in phase III trials in the US, Argentina, Brazil and Germany.14
Challenges in COVID-19 vaccine development
Despite the accelerated process of vaccine development, there are several challenges that may cause a delay in the approval and distribution of a successful COVID-19 vaccine:
1. Safety concerns
The safety of the vaccine is of utmost importance. Any adverse effects of the vaccine could lead to a delay in its approval. For example, the phase III trial of the ChAdOx1 nCoV-19 vaccine by University of Oxford and AstraZeneca was temporarily paused in September 2020 after a participant in the UK developed an unexplained illness. The trial was resumed after a review by the independent safety committee and regulatory authorities.15
2. Efficacy concerns
The efficacy of the vaccine is another important factor. The vaccine should be able to provide sufficient protection against the virus. The US Food and Drug Administration (FDA) has set a minimum efficacy of 50% for a COVID-19 vaccine to be approved.16
3. Manufacturing and distribution challenges
Even if a vaccine is approved, manufacturing and distributing billions of doses worldwide is a huge challenge. The vaccine needs to be produced in large quantities and distributed to all parts of the world. This requires a robust supply chain and cold storage facilities, especially for mRNA vaccines that need to be stored at very low temperatures.17
4. Vaccine hesitancy
Vaccine hesitancy, which is the reluctance or refusal to vaccinate despite the availability of vaccines, is another challenge. A survey conducted in the US in September 2020 found that only about half of Americans would get a COVID-19 vaccine if it was available at that time.18
Conclusion
The development of a COVID-19 vaccine is progressing at an unprecedented pace. Several vaccine candidates have shown promising results in clinical trials and some may be approved for emergency use by the end of 2020 or early 2021. However, it is important to note that even after a vaccine is approved, it will take time to manufacture and distribute it to all parts of the world. In the meantime, it is crucial to continue following public health measures such as wearing masks, practicing social distancing, and washing hands regularly to control the spread of the virus.