- The approval in the US of Jansen’s vaccine, designed as a one-dose therapy, is seen as a “game changer” in the fight against COVID-19.
- Vaccines don't work instantly as it takes weeks to train the body's immune system; most experts believe the best time to test a dose's efficacy is 2 weeks after injection.
- Recent findings show robust immunity generated by a single Pfizer shot (with up to 92% efficacy) in a 9,000-subject Israeli study, boosting arguments for delaying the second dose, and thus widening coverage.
- Scientists are deeply divided over the strategy; one camp cites possible risks to public health, another group cites strong data suggesting that the benefits far outweigh the risks.
Dubai: The landscape of single-dose vaccines against COVID-19 just got more interesting. On Sunday, US health authorities approved the Janssen vaccine as a single-shot against COVID, with 78% efficacy. This is seen as a “game changer” in the global counter-coronavirus drive.
Data from the clinical trials and massive vaccination rollouts lead some experts to make a case for single shots from Pfizer and Moderna vaccines, too. The latter two are messenger RNA vaccines currently being rolled out in North America, Europe and the Middle East as a double dose.
With millions of doses per day being administered, there’s a decent amount of information for data scientists to crunch. Some experts argue this delayed — or “fractional” — dosing, could help the world achieve herd immunity sooner. Other scientists oppose the strategy. Here’s the lowdown on single-dose COVID shots:
Q: Does a single shot really work against COVID-19?
Yes. The efficacy of a single-dose shot against COVID -19 actually stands on solid scientific ground, based on clinical trials and post-trial vaccination data.
Q: What’s the efficacy rate of Janssen single-dose vaccine?
It’s 78% from the Johnson & Johnson arm.
Q: What’s the efficacy of Modern and Pfizer vaccines as a single dose against COVID-19?
Late-stage clinical trials (for Moderna) as well as post-trial studies (for Pfizer) show a rather high vaccine efficacy for a one-dose shot. An efficacy at least 85-92.6% was recorded for Pfizer, taken from a 9,000-subject study in Israel. It was 80.2-92.1% for Moderna (in a 2,000-subject clinical study) following single dose against COVID-19 had been reported.
Q: Why are the Pfizer and Moderna vaccines not approved as single-dose vaccines?
The two companies applied for a double-dose regimen with the US Food and Drug Administration (FDA), before they were approved in December 2020. The standard drug-approval application process requires the completion of 3 stages of clinical trials before a vaccine is approved. The two are currently approved as two-shot vaccines.
Q: What’s the initial vaccine efficacy of the first dose of Pfizer’s BNT162b2 shot?
In the original clinical study conducted by Fernando Polack and colleagues, efficacy after the first dose was calculated at 52.4%, based on data collected during the first 14 days after injection, when immunity would still have been mounting. The same analysis concluded that prior to the second dose — at Day 28 — BNT162b2 has already achieved an efficacy of 92.6%. Immunologists explain that it takes time for a vaccine to "train" the body's immune system to fight a specific pathogen. So it makes more sense to measure immune response only after 14 days, instead of immediately after the first dose.
Q: What does this mean?
Measuring vaccine efficacy immediately after a shot is unrealistic and unsound scientifically, explained Dr. Don Sheppard, Professor of Molecular Mycology and scientist at the Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre. The clinical data showing a 92.6% vaccine efficacy at Day 28 following the first dose is surprisingly high. Even the 70% efficacy of the Oxford Vaccine three weeks after the first dose is impressive.
It's clear, that from a public health perspective, the bang for the buck on that second dose, is to give it to someone who is not immune and get a 90% chance you protect a second person, instead of a couple of digit per cent on that first person.
"It's a risk, but it's a calculated risk that makes a lot of sense. It's clear, that from a public health perspective, the bang for the buck on that second dose, is to give it to someone who is not immune and get a 90% chance you protect a second person, instead of a couple of digit per cent on that first person," Dr Sheppard told the McGill University Health Centre channel on Youtube.
Q: What do experts say about this fact?
Dr Danuta Skowronski and Dr Gaston De Serres, who reviewed Pfizer’s BNT162b2 clinical trial documentation submitted to the FDA wrote for the New England Journal of Medicine: “With such a highly protective first dose, the benefits derived from a scarce supply of vaccine could be maximised by deferring second doses until all priority group members are offered at least one dose.”
• Germany’s Curevac (Phase 3)
• US biotech firm Arcturus Therapeutics Holdings Inc. (Phase 2)
• Thailand’s Chulalongkorn University (Phase 1)
• China’s Academy of Military Science (AMS) collaborating with Walvax Biotechnology and Suzhou Abogen Biosciences (Phase 1)
• Canada’s Providence Therapeutics
• More than a dozen other entities are developing mRNA vaccines (in pre-clinical trials) against COVID-19.
Q: What is the duration of protection after the first dose.
Chen Fang, writing for Infectious Disease Advisor, stated that there's limited data on an alternative vaccine schedule and duration of protection after the first dose. However, Fang cited experts as saying that given the current vaccine shortage, “following the current vaccine schedule provides little short-term benefit”.
Pfizer, for its part, stressed on the importance of gathering scientific data on implemented alternative dosing schedules to ensure vaccines provide the most optimal protection.
Q: What is the UK doing about second dosing?
The UK has adopted as strategy to delay the second dose of both the Oxford/AstraZeneca and Pfizer/BioNTech vaccines so that more people can be vaccinated with their first dose — rather than giving a smaller number of people both doses. It is hoped that this will save more lives, given the current vaccine production shortfalls and delivery challenges with the vaccine rollout.
Q: What did other governments do about it?
Recently, both the German and US governments have stated they do not intend to follow the UK’s lead and delay the second COVID-19 vaccine shot.
Q: What do regulators say about the delay?
The World Health Organisation (WHO), the Centres for Disease Control and Prevention (CDC), as well regulatory bodies such as the Food and Drugs Administration (FDA) in the US and the European Medicines Agency (EMA) advise strict adherence to the vaccination schedules, as prescribed following peer-reviewed studies from Pfizer/BioNTech and Moderna (the other mRNA vaccine) — respectively, 1/22 day and 1/29 day for first and second dose vaccinations.
Q: Do Pfizer and Moderna support the delay strategy?
Q: Why is this an interesting development?
Most people in the world are keen to vaccinate, but the supplies, especially given the two-dose regimen, are simply not enough for everyone. Deliveries to less developed nations are slow, if at all. There’s a great urgency to combat the coronavirus pandemic.
But a single-dose regimen was never considered for the initial global coronavirus vaccine rollout — until now, that is.
Q: Why are single-shots now being considered?
There are a number of reasons:
• First, there are vaccine makers who applied to license their single shots. There are at least 15 others in the pipeline, according to a WHO list updated on February 26, 2021.
On Sunday (February 28, 2021), the US FDA approved the single-shot Janssen COVID-19 vaccine based on 66% to 78% reported efficacy of a single dose from trial data that included up to 60,000 volunteers in 3 continents, including places were emerging new strains became dominant (including the reportedly more virulent variant seen in South Africa).
• Second, a peer-reviewed study involving 9,000 participants (health workers) at Sheba, Israel’s biggest hospital published in The Lancet shows a single Pfizer vaccine shot was 85% to 91% effective between two to four weeks after only one dose.
An earlier review, however, shows a higher efficacy rate for the BNT162b2, at up to 92.6% even before the second dose. Not only that, the vaccines can also be stored in normal freezers without spoiling them — for up to two months, instead of the -70 °C, which was the initially published handling protocol.
Q: What do UAE authorities say about single-dose vaccines/fractional dosing?
A senior UAE health official told Gulf News they will review the scientific data. The UAE approved Pfizer’s two-dose BNT162b2 shot in December.
“The new scientific information in regards to number of doses will be reviewed by the regulatory body and technical committee and the protocols or guidelines will be updated accordingly,” said Dr Farida Al Hosani, Department Manager, Communicable Diseases in Abu Dhabi Public Health Centre and Official Spokesperson for Health Sector in the UAE.
Q: What are the benefits of having single-dose vaccines from multiple makers?
The benefits are manifold:
⬛ For the people facing health risks from the virus, and amidst limited vaccine supplies, approved vaccines have shown to give good protection.
⬛ A single dose immediately doubles the potential coverage of ready vaccines, as well as those current in production.
⬛ Given the unprecedented need to contain the pandemic, a single dose would greatly alleviate the initial global shortfall in vials.
⬛ It affords health authorities the ability to get a full grip on the virus sooner — or before the next strain emerges.
Q: What accounts for the optimism towards a single-dose mRNA vaccine?
Among the immunology researchers, there’s a mix of excitement and guarded optimism building up around the single-dose-mRNA-vaccine-works thesis. Dr F. Perry Wilson, US immunologist who did table-by-table analyses of Moderna’s mRNA-1273 vaccine, explained the significance of a little-known part of the Phase-3 trial data.
Moderna submitted documentation to the FDA. Dr Wilson, a noted clinical researcher at Yale, cited Table 15 of the Moderna submission, showing early efficacy data of the vaccine among those who received only one dose.
Over a 28-day period, as daily infections for the placebo group rose, there was a near-flatline for the vaccinated group.
It was not clear why those volunteers (1,000 in each of the placebo and vaccine groups) only received one dose. Dr Wilson, however, added: “A lot of people are gonna be squinting at this (data) to decide if a single dose is going to be protective or not. Remember, the people here were getting their second dose around 28 days. We’re gonna need more data…But if you want to know if one dose is protective, what it (table) tells us is that immediately after one dose, efficacy is 80%.
“Now, that’s not as good as the overall efficacy (of the two-dose regimen) they reported, but it’s not really a fair comparison. Because we don’t think you should get immune the moment you get the vaccine. You have to build up your immunity.”
Q: Where does the 92% efficacy on single mRNA-1273 dose come from?
Dr Wilson pointed out the data gleaned from a sub-set of 2,000 volunteers (out of the total of 30,000-plus in the Moderna Phase 3 trial), who only received one dose. After 14 days (when immunity should have started kicking in), “only 2 infections were seen in the vaccine group compared to 28 in the placebo group — for an efficacy rate of 92%,” he said.
While the Moderna data on a single-shot efficacy leaves much to be desired in terms of scientific rigour, it’s certainly “fascinating”, said Dr Wilson.
Q: What’s the main criticism against the UK strategy of delaying a single dose?
The UK government’s move has kicked up a debate. Public health, medical, and scientific support had been divided. Some scientists have opposed the delay, especially to the Pfizer vaccine. They cite a lack of evidence of effectiveness of the strategy — as well as potential risks. The main criticism by an experts’ group: the likely fall in neutralising antibody immunity with delayed dose.
Writing for BMJ, Prof Herb F Sewell, Professor of Immunology and Consultant immunologist, University of Nottingham, questioned the wisdom of the delay. There are, however, those who support the “finely balanced decision”, which come from speciality medical royal colleges, the Academy of Medical Sciences, and the British Society of Immunology.
- As the world tries to break free from the pandemic’s grip, a key challenge to vaccine makers is the production of an effective regimen — whether it’s a single or double dose — that could boost the global immunisation drive
- With a single-shot vaccine, if effective, it would get us twice the bang for the buck, compared to double-dose shots currently approved.
- Amidst the emergent coronavirus variants, there are concerns the vaccine efficacy (of both single and double-dose shots) may wane over time.
- Efforts are on from different vaccine makers to “update” their arsenal against the latest mutants.