SINGAPORE – With more than 200 potential Covid-19 vaccines developed worldwide, we are flooded with information on the latest developments every day.
How do we analyze the large amount of information to guide urgent decisions about which vaccines to buy or use?
To gather Singapore’s Covid-19 vaccine portfolio, a committee of experts reviewed more than 40 vaccine candidates over the past seven months.
This involved more than a hundred meetings with companies and academics and a detailed study of thousands of pages of scientific papers, industry reports and protocols.
Balance a vaccine portfolio
Covid-19 spurred the development of an unprecedented number of vaccine platforms, some of which had never before been approved for use in humans.
These include traditional and well-proven approaches that use inactivated whole viruses or virus protein fragments, newer technologies that use nucleic acids (RNA or DNA), and viral vectors mounted on another virus to deliver a coronavirus payload. to the immune system).
From the outset, it was important to address multiple concerns.
This includes which technologies make vaccines better, which are safer, which will be available sooner, and which are easier to manufacture, as billions of doses are needed to protect entire populations.
There are already front runners getting regulatory approval for conditional or emergency use.
However, these may not end up being “best in class” in terms of safety or effectiveness.
There are also concerns about vaccine nationalism and fears that vaccine exports may be stopped by governments and redirected to address their national situation.
Any vaccine portfolio must be based on robust scientific and clinical evidence and diversified appropriately to address political and operational considerations.
Dissect the tests
With all companies in the race presenting their own version of the vaccine, it can be a challenge to choose the best one.
The main consideration is whether a particular vaccine is safe to use.
Vaccines prepare the human body to prevent a real infection and it is not uncommon for some people to experience fever or pain at the injection site, although they tend to recover quickly.
What may be of concern are the rare cases of severe reactions caused by the vaccine or the body’s immune response. Some events are so rare that tens, if not hundreds, of thousands of people need to be vaccinated before this can happen.
Therefore, the risks of Covid-19 infection should be weighed against the rare likelihood of damage from vaccination.
Another important consideration is the proper functioning of the vaccine.
One way to measure this is the potency of the antibody response.
Antibodies are proteins produced by the body that target and neutralize the virus. It is generally believed that the higher the level of these “neutralizing antibodies”, the better the protection provided.
Vaccines also work by activating immune cells, which have different roles.
Some immune cells help in the continuous production of antibodies that lead to more lasting protection, while others trigger “killer cells” that seek out and destroy virus-infected cells.
A detailed study of how the immune system responds to a vaccine allows us to predict its effectiveness.
Preclinical studies conducted in a laboratory with animal models provide us with an insight into how the vaccine may work in humans. Ideally, vaccinated animals achieve a “sterilizing immunity,” where the immune response is powerful enough to get rid of the virus completely.
Vaccines that show promise go on to clinical trials in humans.
In clinical trials, both the safety and efficacy of the vaccine are closely monitored.
The results of people receiving the vaccine are compared with those receiving a placebo. At the end of the trial, the vaccine group should have far fewer cases of disease compared to the placebo group.
Recent reports show that both Pfizer-BioNTech and modern vaccines can achieve a protection rate of approximately 95%, which means that most people who get vaccinated will not get Covid-19, although there are the possibility that the virus may pass. to others.
It is also important to find out how long the protection lasts.
Many patients recovered from Covid-19 continue to have antibodies in their blood even six months later.
To determine how long vaccine protection lasts, clinical trials should continue for at least two years.
Finally, clinical trials evaluate the functioning of a vaccine in different age groups, especially in the elderly, as well as in patients with pre-existing diseases.
Beyond lab testing and clinical trials, there are practical problems to deal with.
The company’s history is important, including whether it has the resources and experience to conduct multicenter testing on continents, with the participation of tens of thousands of participants; its ability to increase the manufacture and distribution of vaccines worldwide.
There are companies with vaccines backed by a wonderful science, but which do not have the means to bring them to the clinic.
Some vaccines require two or more doses, while some selections state that a single dose provides adequate protection. Others require mixing of contents of different vials just before vaccination.
With the need to administer millions of doses, each additional step creates its own set of challenges.
We also need to consider logistics.
Some vaccines are unstable at room temperature and should be sent and stored at temperatures as low as minus 70 ºC.
This requires the creation of an ultra-low temperature freezer farm to house the vaccines, and a coordinated milk is run to distribute them to the vaccination sites.
Finally, vaccines, which are biological products, have a limited shelf life.
This determines how long they can be kept if they are not used immediately.
Through a systematic process of peer review and evaluation, the long list of vaccine candidates has been reduced to a handful.
Singapore’s final portfolio balances considerations of security, efficiency, timeliness, accessibility and implementability, while mitigating the risks of failure.
This required a strict examination of what was being published, reading between the lines of what was not, and making difficult calls based on the best evidence available.
Developments in the coming months will determine whether the right decisions have been made.
About the writers:
Professor Benjamin Seet is CEO of the group (education and research) of the National Healthcare Group (NHG) and adjunct professor in Lee Kong Chian School of Medicine at Nanyang University of Technology.
Professor Ren Ee Chee is an immunologist and principal investigator at the Singapore Immunology Network, under the Science, Technology and Research Agency (A * Star), and an adjunct associate professor at Yong Loo Lin University School of Medicine. Singapore National. .
Both writers are members of the expert committee of the Ministry of Health on vaccination against Covid-19.