The current pandemic of COVID‑19, caused by SARS‑CoV-2 virus is a global epidemiological crisis. The viral infection has affected about 210 countries and territories around the world. In just over 1 year after the pandemic was declared in March 2020, there are more than 130 million cases worldwide and more than 2.8 million deaths. There is also the possibility of the disease becoming endemic and seasonal. Many research groups and companies globally are undertaking efforts to develop a safe and effective vaccines, at an unprecedented speed for the usual phases needed to develop and test a vaccine in humans.
Prior to this pandemic, no vaccine was available for prevention of any coronavirus infection in humans. Previous attempts to develop vaccines for Coronaviridae virus family that infect humans have been for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The vaccines candidates have been tested in animals. As of 2020, there is still no vaccine proven to be safe and effective against SARS or MERS.
Most of the platforms of vaccine candidates for COVID-19 in clinical trials as of the end of 2020 are focused on the coronavirus spike protein and its variants as the primary antigen. Vaccine strategies being rapidly developed involve nucleic acid technologies (RNA and DNA), peptides, recombinant proteins, non-replicating viral vectors, live attenuated viruses and inactivated viruses. Safe and effective coronavirus vaccines were targeted by 2021. Research teams are currently testing candidate vaccines in clinical trials on humans and in preclinical phases in animals.
Several organizations have joined forces in the face of the pandemic with the aim to reduce mortality and severe disease. The Access to COVID-19 Tools (ACT) Accelerator, is a ground-breaking global collaboration to accelerate development, production, and equitable access to COVID-19 tests, treatments, vaccines and health system strengthening. It brings together governments, health organizations, scientists, businesses, civil society and philanthropists. COVAX is part of the ACT Accelerator. As the vaccines pillar of ACT Accelerator, COVAX is a global initiative co-led by the Coalition for Epidemic Preparedness Innovations (CEPI), Gavi, the Vaccine Alliance, and the World Health Organization (WHO).
COVAX works in partnership with governments and manufacturers to ensure COVID-19 vaccines are available worldwide to both higher-income and lower-income countries, once they are licensed and approved. Currently over 10 vaccine candidates are included. The coalition aims to provide two billion doses of vaccine to the most vulnerable people and to health-care workers, especially in poor countries. The pillar also launched the COVAX Facility for global procurement of vaccines with over 180 countries engaged, including Malaysia. Currently, CEPI’s candidates include the companies Inovio, Moderna, CureVac, Institut Pasteur/Merck/Themis, AstraZeneca/University of Oxford, Novavax, University of Hong Kong, Clover Biopharmaceuticals, and University of Queensland/CSL which are part of the COVAX initiative. By end of March 2020, COVAX has delivered vaccines to 70 countries.
In early October 2020, China announced that it had joined COVAX. About 80 other wealthy countries have committed to support the initiative. The Malaysian government has joined the COVAX vaccine access plan. COVAX Facility would provide vaccine doses for ten per cent of the total population, or over three million residents in Malaysia. The plan operates on a two-dose regimen, which means that vaccinating 10 per cent of Malaysia’s population amounts to over six million doses.
Two vaccines co-developed by China pharmaceutical group Sinopharm and other groups was targeted to by the end of 2020. The vaccines were tested in several countries including the United Arab Emirates, Bahrain, Peru and Argentina. Sinopharm said it may have the capacity to produce more than 1 billion doses in 2021. In addition, hundreds of thousands of people in China have been given experimental trial-stage vaccines as part of an emergency inoculation programme launched in July 2020.
There are four categories of vaccines in clinical trials: whole virus, protein subunit, viral vector and nucleic acid (RNA and DNA). Currently more than 80 vaccines are in clinical trials on humans, and more than 20 have reached the final stages. More than 180 candidate vaccines are in preclinical development and investigation in animals. Combining phases of the clinical trial is a way to accelerate vaccine development. For instance, some coronavirus vaccines had undergone Phase 1/2 trials, in which they were tested for the first time on hundreds of people (testing safety and dosage, plus expanded safety trials). Some candidate vaccines have reached phases 3, which is large scale assessment of efficacy and safety. A few vaccines have progressed to phase 4. Development and progress in this area is rapidly emerging.
Leading vaccine candidates that are in at least in Phase 3:
BioNTech, a German company partnered with Pfizer, based in New York, and the Chinese drug company Fosun Pharma to develop an mRNA vaccine.
Johnson & Johnson developed adenovector Ad26 candidate vaccine, which builds on the technology used for Ebola, Zika and HIV vaccines.
AstraZeneca, the British-Swedish company with the University of Oxford developed a viral vector vaccine (“Trojan horse”) based on a chimpanzee adenovirus, called ChAdOx1.
CanSino Biologics, a Chinese company developed a viral vector vaccine based on Ad5 adenovirus, in collaboration with the Institute of Biology at the Academy of Military Medical Sciences.
Moderna in collaboration with the National Institutes of Health, develops vaccines based on messenger RNA (mRNA) to produce viral proteins in the body.
Gamaleya Research Institute, part of Russia’s Ministry of Health, launched clinical trials in June for Gam-Covid-Vac (Sputnik V). The vaccine is based on two adenovirus viral vectors, Ad5 and Ad26, with coronavirus protein.
Wuhan Institute of Biological Products developed an inactivated virus vaccine, which the state-owned Chinese company Sinopharm tested in clinical trials.
Beijing Institute of Biological Products developed an inactivated virus vaccine, also tested by Sinopharm in clinical trials.
Sinovac Biotech, a private Chinese company is testing an inactivated vaccine called CoronaVac.
Vector Institute in Russia developed EpiVacCorona, a vaccine which contains chemically synthesized viral peptide antigens.
Bharat Biotech and the National Institute of Virology in India developed an inactivated vaccine called Covaxin.
Novavax based in Maryland, USA makes vaccines by bioengineering the spike protein and combination into nanoparticles.
Murdoch Children’s Research Institute in Australia is conducting a Phase 3 trial called BRACE, to study the Bacillus Calmette-Guerin vaccine and its protection against the coronavirus. The vaccine is live-attenuated and was developed in the early 1900s as a protection against tuberculosis.
Most of the vaccines currently in use require two doses for a patient to be fully vaccinated. Some of the leading vaccines have been granted early or limited approval, conditional approval or emergency use approval, or full approval in certain countries. Russia became the first country to give regulatory approval to a Covid-19 vaccine (Sputnik V) in August 2020. Ten different COVID-19 vaccines across three platforms have been rolled out and administered across the globe. As of 31 March 2021, more than 593 million vaccine doses have been given worldwide. The Pfizer-BioNTech vaccine is currently being used in 80 countries. Several more countries have approved vaccines but have yet to begin administrations. While vaccine doses remain relatively scarce globally, most countries have focused their early vaccination efforts on priority groups like the clinically vulnerable; people in their 60s, 70s and older; and front-line workers, like doctors and nurses.
The National COVID-19 Immunisation Programme in Malaysia is under the care of the Special Committee for Ensuring Access to COVID-19 Vaccine Supply (JKJAV), co-chaired by the Ministry of Health of Malaysia and the Ministry of Science, Technology and Innovation (MOSTI). This committee was established for the overall planning, implementation and monitoring, to ensure access to the COVID-19 vaccine immediately, safely, perfectly and effectively for the country. The programme commenced in late February 2021, after the first arrival of the Pfizer vaccine on 21 February. CoronaVac vaccine (Sinovac, China) arrived in the country shortly after, while 3.5 million doses of CanSino vaccine to be received in stages from China beginning April 2021. In early April the AstraZeneca vaccine which is supplied under COVAX facility was granted conditional registration. By end of March 2021, 700,000 frontliners have been vaccinated as part of Phase 1 of the national programme. Further information can be accessed at the official JKJAV website, https://www.vaksincovid.gov.my/
Safe and highly effective COVID-19 vaccines are much anticipated in the evolution of this global pandemic. It is possible that there will be multiple partially protective vaccines, conferring immunity that wanes over time. Monitoring the status and results of Phase 3 efficacy trials and Phase 4 post-marketing surveillance (pharmacovigilance) will provide further safety and immunogenicity data on a larger scale. Stringent monitoring for safety, effectiveness and durability of protection will be crucial as more populations are vaccinated.
Many uncertainties remain, and studies on neutralizing antibodies and duration of immunity are still ongoing. It is still unclear the degree to which the vaccines can protect against disease, and also against infection and viral transmission. Even after vaccination, we must not put ourselves and others at risk and must continue to wear masks, practice physical distancing and avoid crowds.
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