Science Talk: Covid-19 vaccines boosted

Growing knowledge of vaccines in real-life experience has enabled Singapore to refine their use

Vaccines are a key weapon in this battle against a mercurial enemy.
Vaccines are a key weapon in this battle against a mercurial enemy.PHOTO: ST FILE

SINGAPORE - It seems a lifetime ago, but it has barely been half a year since the Pfizer-BioNTech vaccine landed on our sunny shores, and was first delivered into the arms of our intrepid clinicians at the National Centre for Infectious Diseases.

Up till last month (April), with shots in hand and safe management measures in place, Singapore was seemingly on the front foot in this fight against Covid-19, with steady progress on vaccinations, tentative steps towards travel bubbles and even the promise of the World Economic Forum (WEF) meeting bringing some light to a dreary year.

If a week is a long time in politics, then a month is an eternity in a pandemic.

With daily unlinked community cases rising over the last weeks, we are now back under significant social restrictions, travel bubbles have popped and the WEF has finally accepted that its party has been well and truly rained on.

Vaccines are a key weapon in this battle against a mercurial enemy.

In December last year, I first wrote about the trustworthiness of vaccines, despite their speedy development.

It is worth reiterating that the initial studies were designed to gather as much robust data, as quickly and as safely as possible, so as to gain expeditious approval and deployment.

In a remarkable feat of drug development, several efforts, notably from the mRNA platforms such as the ones we use in Singapore, were able to demonstrate safety and efficacy, and gain emergency approval in record time.

However, a focused vaccines development package bent on speed to patients has left several gaps in our collective understanding of how to best harness the use of these transcendent assets.

Researchers and companies have not stood still.

Over the last weeks, several developments have been announced that will enable us to use these tools even more effectively.

As Sars-CoV-2 - the virus which causes Covid-19 - evolves and mutates, we too need to expand the use of our weapons, and adapt our tactics.

First, in the middle of this month, both the United States Food and Drug Administration (FDA) and Singapore's Health Sciences Authority (HSA) approved the use of the Pfizer-BioNTech vaccine for adolescents aged 12 to 15 years.

While prioritising the adult cohort study at the start of clinical development, Pfizer-BioNTech rapidly expanded the pivotal phase three study to include over 2,000 adolescents, fully cognisant that in order for herd immunity to be achieved, the large swathe of under-16s could not be ignored.

In filings to the regulators, the Pfizer-BioNTech vaccine demonstrated both exceptional efficacy against Covid-19 illness, and a good safety profile in the 12- to 15-year-old cohort, commensurate with what had been observed in older trial participants.

The vaccine also elicited a strong antibody response in the adolescents, with neutralising antibody levels that were not inferior when compared to young adults aged 16 to 25 years.

This data provides welcome news for Singapore, where the latest outbreak has infiltrated schools, prompting school closures and disruptions to classes.

At the time of writing, the Ministry of Health is working with the Ministry of Education and will provide updates in due course on vaccinations for this school-going age group, but the door is now at least formally open to the possibility.

As at last week, the US Centres for Disease Control and Prevention (CDC) said that at least 600,000 adolescents have received their first dose, barely a week after approval.

It should be noted that Moderna's study in adolescents has also completed recruitment, and both companies have embarked on studies in children below the age of 12.

Next, evolving data from real-world usage has indicated that an extension of the dosing interval between the first and second vaccine doses, beyond the prescribed 21 and 28 days, to up to 12 weeks may be warranted.

An Israeli study on healthcare workers showed that the Pfizer-BioNTech vaccine was effective in providing good to excellent protection for individuals within 28 days after the first dose, reducing infections and illness.

Another recent study by the University of Birmingham and Public Health England, currently in pre-print, established that antibody response in an elderly cohort who received a second dose of vaccine at 11 to 12 weeks from the first dose was as good as, if not higher than, that for those who had received the standard regimen.

A third study, headed by the Mayo Clinic, ran simulations on population health outcomes, comparing the scenarios of providing standard dosing versus prioritising the first dose to a wider population and delaying second doses.


Pfizer vaccines will be placed in a storage facility with capabilities of handling ultra-cold storage at about minus 80 deg C. PHOTO: MINISTRY OF HEALTH

This simulation showed that under certain conditions, for high-efficacy vaccines, this trade-off resulted in lower overall mortality and a public health benefit.

Last, in a quiet announcement last week, the European Medicines Agency approved an expansion of storage conditions for the Pfizer-BioNTech vaccine.

Readers may recall that a key impediment for the deployment of the mRNA vaccines at the beginning was the stringent requirements for ultra-cold storage at minus 70 deg C, and a very limited shelf life once thawed.

With further testing and data, that requirement has been relaxed, as the European agency now extends the storage period at 2 to 8 deg C, after the vaccine has been thawed, from five days to 31 days.

Although the impact to Singapore may not be so significant as our transport chains within the country are short, this may have a major impact in regions where low availability of deep freeze cabinets constrains the use of such vaccines.

In fact, this opens up the real possibility of cross-border supply, where one country can maintain a deep freeze capability, and thaw and send out to other less well-resourced nations, where a 31-day shelf life under normal refrigeration temperatures is far more feasible to manage.

As the Covid-19 pandemic rumbles into its second year, vaccines have now come to the fore as a key weapon to help end it.

The initial core data packages put this weapon into the hands of governments and public health officials expeditiously.

By some estimates, up to 1.5 billion doses have been delivered to hundreds of millions of patients globally. This dwarfs by several orders of magnitude the number of patients who had entered into vaccine trials.

With this, the broad diversity of settings in which vaccines have been used and other formal follow-on studies conducted by companies and researchers, our understanding of vaccine safety, efficacy and product characteristics is far richer today.

At this critical juncture, as Singapore faces another surge in cases, this understanding has allowed our decision-makers to make timely and rational adjustments to our vaccine deployment policies and operations, to optimise public health protection.

• Dr Danny Soon is chief executive officer at the Consortium for Clinical Research and Innovation, Singapore (Cris) and concurrent executive director at the Singapore Clinical Research Institute (SCRI). A veteran of the pharmaceutical sector, he is a member of the Ministry of Health Expert Committee on Covid-19 Vaccination. The views expressed here are his own.