The world is waiting with bated breath as drugmakers race frantically to find a vaccine to fight the novel coronavirus strain (SARS-CoV-2) that causes Covid-19.
We all want our lives to go back to the old normal because this new normal is somewhat suppressive, compared to the freedom we once enjoyed.
As such, the Covid-19 pandemic has launched an urgent race to develop a vaccine at a speed unmatched in the history of vaccine research.
There are currently more than 100 candidate vaccines already in development worldwide, 10 of which are already in clinical development.
But can a vaccine be developed so quickly?
China is leading the race at the moment as its scientists pour their resources into the use of inactivated viruses – a technique that is simple and has been well-established for decades.
It involves growing a virus strain in the laboratory, then using heat or chemicals to destroy its ability to replicate.
Once injected as a vaccine, the immune system recognises the antigens in the inactive virus and reacts by making antibodies that will identify and attack them.
This technique has been used to develop vaccines against diseases such as influenza and hepatitis A.
However, the downside of inactivated vaccines is that immunity can be of limited duration, with more doses required over time.
Hence, most Western scientists are turning to newer methods such as genetic technologies that can accelerate pre-clinical testing in labs and on animals.
“The classical timeline to develop a vaccine lies between 10 to 20 years, and it’s not because we want to be slow.
“It’s a long process of scientific investigation to discover, develop and understand what you need to put into the vaccine.
“The whole development phase, depending on the type of disease you are trying to demonstrate the efficacy for, can sometimes take several years because the attack rate of the disease may not be so high.
“So you need to wait for enough cases (to occur) before you can test it.
“Also, to build a new manufacturing site between the moment you decide to do it and the moment that site has been validated, takes years,” says GlaxoSmithKline (GSK) Vaccines research and development head Emmanuel Hanon.
GSK, the world’s largest vaccine-maker, is one of the players working on vaccines against Covid-19, which has infected more than nine million people and killed almost half a million worldwide to date.
He says, “When this proposal (to develop a vaccine) came, we had to make a quick, important decision.
“Instead of doing our own vaccine and limiting our capacity in terms of manufacturing and speed of development, we have offered our technology to others to help accelerate several vaccine players in the field.
“We are trying to ensure that innovation is not only for developed countries, but even the poorest can also get access to it.”
Focusing on adjuvants
The company’s expertise lies in the use of adjuvants – an efficacy booster that is combined with traditional vaccines to provide better immune response.
An adjuvant is an ingredient such as aluminium salts, oil/water emulsions or liposomes, which is added to some vaccines to create a stronger immune response in those being vaccinated.
Aluminium salts were initially used in the 1930s to 1950s in diphtheria and tetanus vaccines after it was found that they strengthened the body’s immune response to these vaccines.
“It would be arrogant to work on a vaccine on our own, so our strategy is based on partnerships, leveraging on the strengths of the different players in the field of vaccines.
“We are all equal players in this area because this is the first time we are developing a vaccine against the novel coronavirus.
“Our approach is based on pro-ven technology – we know how an adjuvant will react and we know how to use it in a safe way.
“We know which adjuvant is good and needs to be used, we know we can manufacture millions of doses, and we wanted to combine this with other players, e.g. Sanofi, which has a large established capacity in antigen production, which is the other ingredient that needs to be put together to make an effective vaccine,” says Hanon, who spoke to media from around the world in an online briefing a fortnight ago (June 2020).
Presently, GSK is involved in seven collaborations with institutions or firms globally, and last week, entered the clinical development stage with one project.
According to the US Centers for Disease Control and Prevention (CDC), there are six stages of vaccine development:
- Clinical development
- Regulatory review, and
- Approval, manufacturing and quality control.
Once data is accumulated in the clinical development stage, a benefit-risk analysis is carried out for the safety profile of the vaccine.
Hanon adds, “Adjuvants enable antigen-sparing, which means it allows you to minimise the amount of antigen you put into each vaccine dose.
“Consequently, it increases the amount of doses you make available, which will be a major contribution to the Covid-19 vaccine.”
The company laid out plans in May (2020) to produce one billion doses of efficacy boosters for Covid-19 shots next year, compared to the 700 million or so vaccine doses against a range of diseases it usually produces in a year.
“Companies all over the world are making mass efforts to try and accelerate the process, and developing a Covid-19 vaccine in 15-18 months is already close to a miracle,” he says.
“But it is possible because research was done on the Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), which are both (caused by) coronaviruses.
“That research has enabled the identification of what we think is the most credible antigen that should be in the vaccine.
“So that whole discovery phase has been shortened dramatically by scientists deciding that ‘this will be the composition for SARS-CoV-2’.
“Secondly, along with the massive ongoing collaborations, there are new technologies in the field of vaccinology that has also saved an additional few years.
“In this pandemic, the attack rate of the disease is much higher, so we can hope to shorten the testing efficacy.
“When you combine all this together, you have shorter timelines to develop the vaccine.”
A genetic vaccine
Another technology that is being tried is the synthetic Self-Amplifying mRNA (SAM).
“SAM is the genetic code of the antigen; you plug it into a lipid nanoparticle and inject into the recipient.
“The antigen produced will trigger an immune response.
“This is a revolution in the field of vaccinology,” says Hanon.
Basically, once injected in the body, the SAM molecule will replicate (amplify) itself and use the mechanisms of the body’s own cells to produce the antigens of the disease pathogen.
These antigens mimic an early-stage infection and trigger the body’s immune response, generating immune memory for future protection against the pathogen, but without causing disease.
Thus, the human body becomes the factory for its own vaccine.
Owing to its self-amplification and built-in adjuvant properties, SAM can produce sufficient viral antigen to create a strong and sustained immune response, without the need for additional substances that enhance the body’s immune response to the antigens used on the vaccine.
While the world expects many Covid-19 vaccines to emerge, will a single vaccination be enough to last a lifetime?
“This is part of the unknown,” says Hanon.
“Prior to MERS, SARS and Covid-19, humans who were already vaccinated were infected recurrently during the flu season by coronaviruses.
“Sometimes, when you get a cold, the virus may not necessarily be the respiratory syncytial virus (RSV) or a rhinovirus.
“It could be a strain of the coronavirus – usually, the infection is restricted to the upper respiratory tract and creates a cold.
“We have no idea at this stage, if you are vaccinated against SARS-CoV-2, whether you will just get a mild cold upon infection or whether this disease will remain a severe threat.
“It really depends on the persistence of the immunity.”
The coronavirus is the cause of about 20% of all colds, and thus far, no vaccine is commercially available for any of the coronavirus strains.
He says, “Our mission is to deliver life-saving vaccines, and for that, we need to accumulate a sufficient amount of data in humans, not only on a vaccine’s efficacy, but also on its safety to be used on a large scale.
“We need to ensure people are comfortable in getting vaccinated.
“It’s the third time humanity is being threatened by a coronavirus. Each time, it’s a slightly different virus.
“With the evolution of science, we can identify the path of the antigen that is shared by coronaviruses.
“However, the risk of pandemics is now increasing progressively, so we need to be prepared for other coronaviruses as well.
“Perhaps in the future, any credible research and development organisation could investigate further.”
Maintain your vaccinations
It is important that vaccines are used wisely and vaccination schedules are adhered to.
When there is a drop in vaccine coverage, there is a risk of an outbreak of vaccine-preventable diseases.
Every year, almost three million deaths are prevented due to vaccinations.
“When we have an infection, there is a (foreign) microbe that is replicating in our body, ready to stimulate our immune system to produce a defence.
“This defence is based on specific components of white cells or antibodies.
“When this happens, our body will retain some level of memory about this specific microbe, and when we face a threat again, it will be easy to defend our body and avoid falling sick.
“Vaccines work the same way, but without producing symptoms.
“It stimulates our immune system, but of course, vaccines are not perfect and may not work at the same level over time.
“So we have to remind our immune system by using boosters to help it keep up to date and protect the body from infection.
“If the vaccine is stopped, the diseases may surface again as in the case of measles,” says GSK Vaccines scientific affairs and public health head Dr Otavio Augusto Leite Cintra.
He points out that the strength of our immune system varies over time.
During childhood, the immune system is not quite strong; in adults, it gets more robust, and when we get older, it gets weak again.
“Our immune system needs constant reminders and that’s why we have to boost it, although not all vaccines need boosters.
“It’s like learning a language. You may have learnt French in primary school, and 20 years later, you may not remember much unless you brush up on it,” he says.
GSK Vaccines scientific affairs and public health director François Meurice says: “A lot of diseases need a high coverage of vaccine to keep them under control.
“For example, in measles, each person can infect up to 18 others (the highest known number of transmissibility); in MERS, it is below zero and the transmission of disease is slow.
“In Covid-19, the fatality rate is an important feature as older adults have the highest fatality.
“The World Health Organization and other institutions are convinced that the likelihood of pandemics is increasing due to population density, close contact with animals and other elements.
“Neglecting a vaccination programme can put people at risk later on and this is not the right time to suffer from vaccine-preventable diseases.”