Since its first imported case of COVID-19 on January 23, Singapore has experienced a surge in its confirmed cases. To date, there have been more than 30,000 cases in the city-state, which have contributed to the global tally of over 5 million cases and 330,000 deaths. Despite social distancing measures and contact tracing efforts to limit its spread, the Coronavirus continues to ravage global populations. This can be attributed to the fact that COVID-19 is a novel virus—anyone who is exposed to it will likely become infected as they do not have prior immunity. Hence, it has become increasingly urgent to develop a solution to this escalating crisis, one that comes in the form of a vaccine.
How Do Vaccines Work Against COVID-19?
Vaccines boost a body’s immunity to particular viruses, rendering it less susceptible to infection and disease. It does this by training a body’s immune system to recognise the virus it is made for, or at least some component of it, and to subsequently destroy the virus before it creates an infection.
When a vaccine is introduced into the body, it delivers a signature element of the virus—usually a unique protein coating—to the immune system. When the body comes into contact with the virus, an immune response is triggered. Thousands of binding antibodies are produced, and stick to the virus. However, not all of such antibodies can neutralise the virus. Only a special type of antibodies can do so: neutralising antibodies. Neutralising antibodies are designed to identify the specific virus that is introduced by the vaccine, after which it will bind to the virus and stop it from infecting other healthy cells. It is thought to be vital in acquiring protection against targeted viruses. Hence, an effective vaccine stimulates the production of neutralising antibodies that circulate throughout the bloodstream. They act as tiny guards that defend and protect the body against a type of virus. In the event that this virus enters the body, these antibodies will attack and paralyse it. Following which, these antibodies signal the immune cells to provide backup in completely destroying the virus.
When it comes to COVID-19, the aim of candidate vaccines is to encourage the immune system to produce antibodies that detect and destroy it. An effective way of doing so is to induce the creation of antibodies that target the COVID-19’s spike proteins. These are crown-like features on the surface of the Coronavirus which allows it to attach onto the healthy cells of a host. These spike proteins enable the virus to hijack the cell’s activities to produce copies of itself, which will be spread to infect other healthy cells. When a vaccine is successful in producing antibodies that can recognise and annihilate the COVID-19 virus, it prevents an individual from becoming infected with it. This not only gives the individual immunity to COVID-19, it also stops the individual from becoming a vector that facilitates the spread of the virus to other healthy individuals.
What Types of Vaccines Are Being Explored for Use Against COVID-19?
There are currently 5 kinds of vaccine platforms that are being researched as a cure for COVID-19: live-attenuated vaccines, inactivated vaccines, viral vector-based vaccines, subunit vaccines, and RNA and DNA vaccines. Of these, all but the live-attenuated vaccines have made it into clinical evaluation—the trial of vaccines on human subjects.
Live-attenuated vaccines
As the name live-attenuated vaccines suggest, these vaccines use whole strands of weakened live viruses to mimic a real infection. The biggest benefit this poses is its ability to produce the exact same types of antibodies as a real infection would. Ideally, this better builds up the immune system to fight the Coronavirus. However, there are high risks involved. As the virus is live, it can still reproduce itself, which can cause severe reactions in certain people. Thus, highly skilled scientists and very specialised laboratories are required to produce these vaccines safely and accurately. As a result, it is extremely difficult for such vaccines to be mass produced. Yet, such vaccines have been used for Chickenpox and Typhoid.
Inactivated vaccines
While inactivated vaccines also use whole strands of the virus, these viruses are effectively dead. Typically, they are inactivated by heat or the use of chemicals. They are less efficient for training the immune system when compared to live-attenuated vaccines as they elicit a weaker immune response. Thus, they may require several doses or booster shots to become fully effective. Nevertheless, they have its benefits. They pose a lower risk of severe reaction and are relatively easier to manufacture. This vaccine type has been used to create immunity against Polio and Hepatitis A.
Viral vector-based vaccines
Viral vector-based vaccines consist of a weakened or harmless virus that is engineered to contain a component of the target virus. For a vaccine targeted at the COVID-19 virus, this could mean engineering the harmless backbone virus to produce spike proteins. This allows the immune system to produce antibodies that specifically target this characteristically important feature of the virus. The Ebola vaccine was created through this method.
Subunit vaccines
Subunit vaccines are “bare-bones” vaccines that only contain an isolated element of the target virus to induce an immune response. For such COVID-19 vaccines, the spike protein is often a popular choice. They are an established vaccine platform and are commonly used for HPV vaccines.
RNA and DNA vaccines
RNA and DNA vaccines are the latest to join the vaccine family. Although there is currently no approved vaccine that utilises this approach, researchers are still hopeful about their potential. These vaccines contain the genetic material of the target virus, either in the form of RNA or DNA. When received by the healthy cells of a host, it triggers the production of viral proteins that generate antibodies that can detect and attack the target virus.
Which Are the More Promising Vaccines for COVID-19?
As of May 22, the World Health Organization (WHO) has identified 10 candidate vaccines in clinical evaluation with 114 more in preclinical valuation. Of the 10 candidate vaccines in clinical evaluation, 5 are from China, 3 are from the United States, 1 is jointly produced by the United States, India, and the United Kingdom, and another is jointly produced by the United States, Germany, and China.
Today, 2 of these candidate vaccines stand out from the crowd.
Moderna Incorporated
The first is the potential vaccine developed by Moderna Inc., a biotech company in the United States, in collaboration with the United States’ National Institute of Allergy and Infectious Diseases. It uses the messenger RNA approach in its vaccines to build immunity in its recipients. The company has been engaged in clinical trials since March, and is the first to release data on human trials in the field of COVID-19 vaccine testing. In its early-stage human trials, Moderna’s Coronavirus vaccine successfully produced COVID-19 antibodies in all 45 of its participants. Each participant received either a 25, 100, or 250 microgram dose of the vaccine, which were given in 2 doses, around 28 days apart. Two weeks after the second dose, it was found that the level of binding antibodies in those given 25 micrograms were at similar levels to those who had recovered from the Coronavirus. Those given 100 micrograms were observed to have antibodies that “significantly exceeded levels” in recovered patients. Furthermore, the vaccine generated neutralising antibodies (the most important part of an effective vaccine) against COVID-19 in at least 8 participants. The company shared that its vaccine was generally safe and well tolerated by the recipients.
Moderna Inc. has concluded the first phase of its human trials and is set to begin its second phase that would include 600 participants. Its third phase is expected to commence in July. If the vaccine is found to be successful, it could be mass produced and put on the market in early 2021.
Oxford University
The second vaccine in the spotlight is the one developed by the team spearheaded by Oxford University. The Oxford team had a big head start developing their vaccines compared to other teams. This comes as a result of having proved in previous vaccinations—including one done last year against another Coronavirus—that their vaccine approach was safe for use in humans. The Oxford group was thus able to bypass the small clinical safety trials that other teams had to undergo. This has allowed them to schedule further tests on their COVID-19 vaccine, involving more than 6,000 participants by the end of May. Upon emergency approval from regulators, the group shared that a few million doses of their vaccine could be available come September, should it be proven effective. This means that the Oxford group could potentially deliver a vaccine a few months earlier than its competitors.
Last month, 6 rhesus macaque monkeys were administered a single dosage of the Oxford vaccine, following which they were exposed to large quantities of the Coronavirus. Unvaccinated monkeys who were exposed to such quantities of the virus were all found to become infected by the disease. However, the 6 vaccinated monkeys were observed to be in the pink of health more than 28 days later. These 6 monkeys were discovered to have developed protective antibodies within those 28 days. Some of them developed those antibodies even earlier, at the 14-day mark. Though this success is perceived as good news to many, it is important to note that many vaccines that have protected monkeys during laboratorial trials ultimately failed to do the same for humans.
Yet in recent times, the Oxford team has highlighted some interesting challenges. The team has reported that a decline in COVID-19 infection rates will make it increasingly hard to prove the efficacy of its vaccine. Professor Adrian Hill, the director of the University’s Jenner Institute said that “It’s a race against the virus disappearing, and against time”. He added on, “We said earlier in the year that there was an 80% chance of developing an effective vaccine by September. But at the moment, there’s a 50% chance that we get no result at all”. Professor Hill postulated that fewer than 50 of its 10,000 vaccine trial volunteers will be infected with the virus in the week to come. If less than 20 individuals catch the virus, the results of the vaccine trial will be inconclusive.
How is Singapore Contributing to Global Efforts to Find a Vaccine?
Although Singapore is not fronting any COVID-19 vaccine of its own, its researchers are hard at work collaborating with overseas players to contribute to the global vaccine effort.
Duke-NUS Medical School
The Duke-NUS Medical School is partnering closely with American-based medical company Arcturus Therapeutics to work on a COVID-19 vaccine. Similar to Moderna’s vaccine, the partnership is striving towards a messenger RNA vaccine platform to boost the immune system of its recipients against COVID-19. According to Patrick Casey, the senior vice-dean at Duke-NUS’ Office of Research, the school was approached by Arcturus Therapeutics in February to work on the vaccine. “We have the expertise, we have the people who knew what they’re doing, and the outside world has confidence in their ability to really do this well,” he remarked.
While Arcturus Therapeutics takes charge of developing the vaccine and testing it on live animals, Duke-NUS will be responsible for analysing the test results to determine the efficacy of the vaccine. Professor Ooi Eng Eong, deputy director of the school’s emerging infectious diseases programme, remarked that 5 weeks into the testing, results have been promising. “The amount of antibodies that one dose of the vaccine has been generating is much better than what patients generate after Covid-19. We’re quite pleased with the results,” he said. The team is hopeful that it will be able to proceed with human trials for its vaccine by September this year.
Esco Aster
Home-grown company Esco Aster, which specializes in vaccine, cell, and gene-therapy development, is also teaming up with Vivaldi Biosciences, another American-based biotech company to create a vaccine that protects against both COVID-19 and the flu. The unique feature of this vaccine lies in its ability to be easily adapted to mutations in the Coronavirus. In essence, the vaccine can be quickly modified within a span of 3 weeks when a mutation in the COVID-19 virus is detected. Another unique point of this vaccine is how it can be delivered to recipients via a nasal spray, which mimics a natural mode of viral transmission.
The team’s goal is to commence animal testing in 2 to 3 months, with the hopes that their vaccine will get the go ahead for human trials in the next 6 months.
Why Does it Take So Long to Develop Vaccines?
Usually, it can take around an average of 10 to 15 years to develop and manufacture a vaccine. In some cases, as with the HIV virus, a vaccine has yet to be developed. This is simply because researchers have to be certain that the treatment is safe for use on a large group of humans. In order for this to occur, vaccines have to undergo numerous phases of development before they gain approval for usage. Preclinical studies have to be done before animal testings are conducted to determine the vaccine’s safety, potency, and general effectiveness. This is then followed by clinical trials on humans and quality control measures. Even when these are completed, gaining approval itself from the relevant authorities takes time.
Other factors that prolong the creation of a vaccine include the complexity of the disease as well as the intricacies of the immune system, which responses to both the disease and the vaccine.
Can Vaccines Really Prevent Me from Getting COVID-19?
The truth is, the topic of telling whether someone is 100% guaranteed protection from contracting the COVID-19 virus remains a hotly debated one. Although some believe that the presence of COVID-19 specific antibodies grants one immunity from the virus, the WHO had announced in April there is no evidence that those who have recovered from the Coronavirus and have the requisite antibodies would be protected from reinfection.
According to experts like Professor Wang Linfa of Duke-NUS Medical School, treatments that induce neutralising antibodies—such as vaccines—are considered a “best we can get” approach. They have a history of giving one protection from infectious diseases, though they have yet to be officially declared protected by the WHO. He mentioned that “In most cases, neutralising antibodies equal protection, or are the best indicator of protection (from the virus)… It is not a perfect indicator or biomarker for protection (from Covid-19), but it is as good as you can get right now… We have to be realistic, either you do nothing or do something.”
Why Are Private Companies, Not Governments, at the Forefront of Vaccine Development?
For starters, private firms do not usually experience the same levels of bureaucracy and red tape faced by governments worldwide. In this view, they have greater flexibility to conduct the required research and clinical trials in a more efficient manner. Thus, they are more likely to produce vaccines at a much quicker pace.
Secondly, private companies are profit motivated. They are therefore inclined to participate in such development efforts as producing a COVID-19 vaccine at this time would signal coveted government funding for their costly research. It might also mean the ability to gain exclusive licences to manufacture and market the drug in the future.
