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SINGAPORE – With more than 200 potential Covid-19 vaccines being developed globally, we are inundated every day with news about the latest developments.
How do we scoff at the wealth of information to guide urgent decisions about which vaccines to buy or use?
To put together Singapore’s Covid-19 vaccine portfolio, a committee of experts reviewed more than 40 candidate vaccines over the past seven months.
This involved more than one hundred meetings with companies and academics, and the detailed study of thousands of pages of scientific articles, industry reports and protocols.
Balancing a Vaccine Portfolio
Covid-19 fueled the development of an unprecedented number of vaccine platforms, some of which have never before been approved for use in humans.
These include traditional and well-tested approaches that use inactivated whole viruses or virus protein fragments, newer technologies that employ nucleic acids (RNA or DNA), and viral vectors (mounted on another virus to deliver a coronavirus RNA payload to the system. immunological).
From the beginning, it was important to address multiple concerns.
This includes which technologies produce better vaccines, which are safer, which will be available sooner and which are easier to manufacture, given that billions of doses are needed to protect entire populations.
Already there are pioneers obtaining regulatory approval for conditional or emergency use.
However, these may not ultimately end up as “best in class” in terms of safety or efficacy.
There are also concerns about vaccine nationalism and fears that governments will halt the export of vaccines and redirect it to address their national situation.
Any vaccine portfolio must be based on strong scientific and clinical evidence and adequately diversified to address policy and operational considerations.
Dissecting the evidence
With each company in the race coming up with its own version of a vaccine, choosing the best one can be a challenge.
The main consideration is whether a particular vaccine is safe to use.
Vaccines prepare the human body to defend itself against a real infection, and it is not uncommon for some people to experience a fever or pain at the injection site, although they tend to recover quickly.
What may be of concern are rare cases of serious 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 receive the vaccine before this happens.
Therefore, it is necessary to weigh the risks of Covid-19 infection against the rare probability of harm from vaccination.
Another important consideration is how well the vaccine works.
One way to measure this is the strength of the antibody response.
Antibodies are proteins made by the body that target and neutralize the virus. It is generally thought that the higher the level of such “neutralizing antibodies”, the better the protection provided.
Vaccines also work by activating immune cells, which perform different functions.
Some immune cells help with the continuous production of antibodies that lead to longer-lasting protection, while others activate “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 using animal models give us an idea of how the vaccine may work in humans. Ideally, vaccinated animals achieve “sterilizing immunity” where the immune response is powerful enough to eliminate the virus completely.
Vaccines that show promise are going into human clinical trials.
In clinical trials, both the safety and efficacy of the vaccine are closely monitored.
These compare the results in people who receive the vaccine with those who receive a placebo. At the end of the trial, the vaccine group should have far fewer cases of illness compared to the placebo group.
Recent reports show that both the Pfizer-BioNTech and Moderna vaccines can achieve a protection rate of around 95 percent, which means that most people who get vaccinated will not contract Covid-19, although there is a chance that still can transmit the virus. to others.
It is also important to know how long the protection lasts.
Many recovered Covid-19 patients continue to have antibodies in their blood even six months later.
To determine how long the protection of the vaccine lasts, clinical trials must continue for at least two years.
Finally, clinical trials evaluate how well a vaccine works in different age groups, particularly the elderly, as well as in patients with pre-existing diseases.
Practical considerations
Beyond laboratory tests and clinical trials, there are practical problems to deal with.
The company’s track record is important, even if it has the resources and experience to conduct multicenter trials on all continents, involving tens of thousands of participants; its ability to expand the manufacturing and distribution of vaccines globally.
There are companies with vaccine candidates backed by wonderful science, but lack the means to bring them to the clinic.
Some vaccines require two or more doses, while a few claim that a single dose provides adequate protection. Others require that the contents of different vials be mixed just before vaccination.
With the need to administer millions of doses, each additional step creates its own set of challenges.
We must also consider the logistics.
Several vaccines are unstable at room temperature and must be shipped and stored at temperatures as low as minus 70 ° C.
This requires the installation of a farm of ultra-low temperature freezers to house the vaccines, and closely coordinated milk cycles to distribute them to the vaccination sites.
Finally, vaccines, being 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 candidate vaccines has finally been narrowed down to a few.
Singapore’s final portfolio balances security, efficiency, timeliness, accessibility, and implementation considerations, while mitigating the risks of failure.
This required close scrutiny of what was published, reading between the lines of what was not published, and making difficult decisions based on the best available evidence.
The events of the next few months will determine whether the right decisions were made.
About the writers:
Professor Benjamin Seet is deputy executive director of the group (education and research) of the National Healthcare Group (NHG) and adjunct professor at the Lee Kong Chian School of Medicine of Nanyang Technological University.
Professor Ren Ee Chee is an Immunologist and Principal Investigator at the Singapore Immunology Network, under the Agency for Science, Technology and Research (A * Star), and Adjunct Associate Professor at the Yong Loo Lin School of Medicine, National University from Singapore. .
Both writers are members of the expert committee of the Ministry of Health on vaccination against Covid-19.
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