COVID-19: An Outline of the Various Candidate Vaccines
The COVID-19 pandemic has crippled the world economies with more than 65.2 million confirmed cases and more than 1.5 million deaths already reported as of December 4, 2020. The outbreak has engulfed 212 countries and territories globally, along with two international conveyances.
India has recorded a staggering 9.5 million cases and 139,188 deaths as of December 4, according to the Ministry of Health and Family Welfare.
Yet, the scientific community has displayed immense alacrity in developing a COVID-19 vaccine, marking record turnaround time in human history. Given that there was no antidote to the virus, the most optimistic predictions were made for a vaccine around the middle of 2021. As per the World Health Organisation (WHO), the average time to produce a vaccine and make it available for public use has been 16 years until now. The most rapid vaccine development so far has been of the mumps vaccine which took nearly 4 years to get all legit permissions and licensing.
WHO’s ‘Solidarity’ Initiative
As countries around the world are trying to stamp out COVID-19 outbreak, the WHO, in association with its partners, has pulled efforts through its unique ‘Solidarity’ initiative. Solidarity is an international clinical trial campaign to facilitate the search and identification of an effective COVID-19 treatment.
In the same light, WHO is accelerating its assistance for the research, development, evaluation and availability of a safe and effective COVID-19 vaccine. The organization has ramped up collaborations and is convening vital communications within the research community and beyond.
WHO endeavors to run clinical trials of several vaccines as nothing is known about their efficacy and safety in advance. The motto is that the more the number of candidate vaccines tested, the higher are the chances of one turning out to be successful. WHO’s target remains to test a vaccine in its early stage of development. Another big challenge that is encountered is how to scale up the production to meet the demands of the whole world. In this direction, WHO continuously aligns R&D, fast-track regulatory approvals and productions to ensure that the global population gets a vaccine as soon as possible.
So far, more than 120 vaccines have been presented to WHO by different countries around the world. The organization is closely examining and tracking details, including the type and progress of each vaccine. At the moment, 87 vaccines are in the preclinical stage being investigated in animals, and 58 vaccines are in the middle of human trials. Here is a clear-cut breakdown:
- Phase 1: 41 vaccines -Being tested for safety and dosage
- Phase 2: 17 vaccines -Undergoing expanded safety trials
- Phase 3: 13 vaccinesIn the middle of large-scale efficacy tests
- Limited: 7 vaccines -Undergoing large-scale efficacy tests
- Approved: 0 vaccine -No vaccine has been officially approved for full use as yet
Simultaneously, WHO has pulled off ‘Global Target Product Profile’ (TPPs) as a set of guidelines for vaccine developers that lay out the minimum and desirable traits of what are characterized as safe and effective vaccines.
TPPs focus on two different kinds of vaccines:
- Vaccines for protection of individuals at higher risk, such as healthcare workers
- Vaccines with rapid onset of immunity to be used in response to the widespread outbreak
Further, WHO has prepared ‘A Coordinated Global Research Roadmap: 2019 Novel Coronavirus’ that underlines goals of global R&D, proposed strategic approaches, critical actions, immediate steps to control the pandemic, selected knowledge gaps, cross-cutting research priorities, innovation actions and many other aspects related to the scientific research, and contributions to control the outbreak.
Notably, WHO has also defined a ‘Draft Landscape of COVID-19 Candidate Vaccines’ that enlists the various potential vaccines for coronavirus along with their current status of clinical evaluation or regulatory norms. While most of the candidate vaccines are in the preclinical stage, those undergoing clinical trials and expected to be approved for widespread use are discussed below:
Oxford-AstraZeneca’s ChAdOx1 Vaccine:
Scientists at the Jenner Institute, the University of Oxford, have developed this vaccine which is a reinvention of a previous vaccine against an earlier coronavirus strain. Previous trials involving similar inoculations were found to be harmless for humans.
The National Institutes of Health, Rocky Mountain Laboratories, Montana inoculated six rhesus macaque monkeys with single doses of the vaccine and found that the monkeys recovered completely after exposure to heavy amounts of the Sars-COV-2 virus. Following validation of the safety of the vaccine in animal trials, researchers initiated its human trials on April 23. Since then, the vaccine has successfully gone through each stage of trials meant for a vaccine, including Phase III trials involving 30,000 volunteers.
At no point, its safety has been compromised. Yet, strikingly, years of hold-ups between each phase were missing in the case of the Oxford-AstraZeneca vaccine, which explains why it could be developed in just a few months. The vaccine has reached its current status in 10 months, compressing processes that typically take around a decade. The impressive pace can be attributed to a scientifically-dedicated team, the inclination and availability of participants, and timely financial grants. But what stands out is that the vaccine was not required to be created from the scratch. Scientists had already started making vaccines for SARS and MERS, viruses belonging to the coronavirus family, in the wake of the 2003 and 2012 outbreaks. However, those efforts were halted then when the pandemics waned, and resumed now for the novel coronavirus.
Further, the Oxford-AstraZeneca team has reasons to be optimistic about the speedy regulatory approval and manufacture of the vaccine. Regulators were roped in early on, even before the trials were completely over. The UK has four million doses ready-to-use already and has pre-ordered 100 million doses. The pharmaceutical giant partner, AstraZeneca had also begun the production of the vaccine long back, even before the trial results and plans to come up with three billion doses in the coming year. Finally, the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK is undertaking "rolling reviews" of the safety, efficacy and manufacturing standards of the vaccine, giving us hopes of a final decision on vaccine use to be out soon.
In a big relief, the team has been working closely with various groups and philanthropists to ensure worldwide supply, including in less-privileged countries. Prof. Sarah Gilbert is the Lead Researcher along with Prof. Andrew Pollard, Prof. Teresa Lambe, Dr. Sandy Douglas, Dr. Catherine Green and Prof. Adrian Hill. From India, the Serum Institute of India (SII) has been involved in the trials of the Oxford-AstraZeneca vaccine.
Moderna’s LNP-Encapsulated mRNA Vaccine:
Boston-based Moderna tied up with investigators at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC) to develop mRNA, a potential nCoV-19 vaccine, based on a genetic molecule called messenger RNA (mRNA). mRNA carries out the essential function of transferring instructions stored in DNA to create proteins required in each living cell in the human body. An mRNA drug would instruct the cells in our system to produce proteins that could provoke an immune response against a disease. Previously, Moderna joined hands with the NIH on a MERS-CoV vaccine which is a different kind of coronavirus than Sars-COV-2. The company has tested mRNA vaccines for several diseases though never launched one into the market.
Moderna Inc. is the first firm that went ahead for human trials of a COVID-19 vaccine on March 16. Following promising results from those trials, the Phase 3 testing involving 30,000 volunteers began on July 27. On November 16, the first preliminary data from clinical trials was released and scientists put the estimated efficacy rate of the vaccine around 94.1 percent.
Currently, Moderna has already applied for emergency use authorization to the Food and Drug Administration (FDA) in the US, which if granted would mean that the first injections may start on December 21. Meanwhile, Moderna has also entered into deals with various countries, including Qatar, Canada and Japan to facilitate the vaccine, following approval. Its pact with the European Commission promises to provide up to 160 million doses of the vaccine.
CanSino’s Adenovirus Type 5 Vector Vaccine:
Developed by the Chinese firm, CanSino Biologics Inc. and Beijing Institute of Biotechnology jointly, the vaccine uses a non-replicating viral vector as its platform to develop a 'Adenovirus type 5' candidate vaccine. This is similar to non-corona candidates, such as an Ebola vaccine. Adenoviruses are common viruses that can introduce potential antigens to trigger the production of disease-fighting antibodies. It was CanSino Biologics Inc., in collaboration with the Chinese Academy of Military Medical Science's Bioengineering Institute, that had developed an Ebola vaccine in 2017.
Promising results of the vaccine’s Phase I and Phase II clinical trials were released in May and July, respectively, testifying a strong immune response. On June 25, the Chinese military, in an unprecedented move, approved the vaccine as a “specially needed drug” for the span of a year. The Phase 3 trials commenced in August in different countries, including Russia, Saudi Arabia and Pakistan.
Pfizer-BioNTech’s BNT162b2 Vaccine:
After months of stringent clinical trials and a comprehensive analysis of data by experts, the MHRA (UK) has given a nod to Pfizer-BioNTech’s vaccine for widespread use. The vaccine has been tested to meet optimum standards of safety, efficacy and quality. In effect, the UK has become the first Western country to approve a COVID-19 vaccine, and Pfizer-BioNTech shot marks the fastest vaccine development for a pandemic after adherence to all the mandatory stages (the Chinese and Russian vaccines were approved prior to Phase III trials).
Additionally, Pfizer and BioNTech have applied for an emergency use license from the U.S. FDA, which is expected to take weeks to review the application. Adding to the good news is that the vaccine claims to offer close to 95 percent protection against the coronavirus.
The first dosing of the New York-based Pfizer’s and its German partner BioNTech’s BNT162b2 vaccine had taken place on trial participants way back on May 5. The vaccine is an mRNA (Messenger Ribonucleic acid) immunisation. mRNA is naturally present in all living cells and acts like a messenger carrying information embedded in DNA. mRNA vaccines are said to use tiny particles of COVID-19’s genetic code to produce the virus inside the body. This helps the immune system identify the virus as a foreign body, and attack it with antibodies.
Precisely, it was the use of the novel mRNA technology that explains the rapid development of Pfizer and Moderna vaccines. With genetic material mRNA, companies are not required to produce weakened pathogens or protein for the vaccine, a process that would otherwise have consumed months.
Pfizer and BioNTech had started inking deals to supply large orders of the vaccine to different countries a few months back. The US government had entered into a contract for procuring 100 million doses by December along with the option to acquire 500 million doses additionally. European Union struck a deal to purchase 200 million doses and Japan for 120 million doses. Pfizer and BioNTech are eyeing the production of over 1.3 billion doses of the vaccine globally by the end of 2021, provided approval for worldwide use is granted.