US and UK diverge over critical COVID-19 vaccine dose strategy
Health authorities in the United Kingdom have recommended extending dosing schedules for approved COVID-19 vaccines, suggesting one dose offers enough short-term protection despite clinical trials only testing two-dose regimes. Authorities in the United States, however, claim this dosing change is unproven, risky and premature.
Two COVID-19 vaccines have been approved for emergency use in the UK. Both were trialed using a two-dose schedule, with the second dose administered three to four weeks after the first.
New advice from the Joint Committee on Vaccination and Immunisation (JCVI) is now suggesting the second dose of both approved vaccines can be delayed for up to 12 weeks. While clinical trial data is not clear on how this change to the tested dosing schedule will affect long-term immunity, the JCVI advice presents a utilitarian solution to the current wave of virus transmission spreading across the UK.
“The four UK Chief Medical Officers agree with the JCVI that at this stage of the pandemic prioritising the first doses of vaccine for as many people as possible on the priority list will protect the greatest number of at risk people overall in the shortest possible time and will have the greatest impact on reducing mortality, severe disease and hospitalisations and in protecting the NHS and equivalent health services,” declares a UK government statement.
In response to the UK government decision, the US Food & Drug Administration (FDA) released a statement claiming it does not recommend changes to currently approved COVID-19 vaccine dosing schedules, and called any changes to dosing schedules, “premature and not rooted solidly in the available evidence.”
The FDA’s statement claims there is no data from clinical trials to suggest anything definitive about the depth or duration of protection one would receive from a single vaccine dose.
“We know that some of these discussions about changing the dosing schedule or dose are based on a belief that changing the dose or dosing schedule can help get more vaccine to the public faster,” the FDA statement notes. “However, making such changes that are not supported by adequate scientific evidence may ultimately be counterproductive to public health.”
Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said in an interview with CNN the US will not be following the UK in delaying a second dose for COVID-19 vaccines. He added that while he understood the argument for delaying a second dose, there simply is no clear evidence from clinical trials that one dose generates effective protection.
A joint statement from Pfizer and BioNTech, the developers of one of the COVID-19 vaccines approved for use in the US and UK, affirms Fauci’s sentiment. The statement says since the clinical trial investigated a two-dose schedule, there is no evidence as to whether a single dose offers any level of protection past three weeks.
“The safety and efficacy of the vaccine has not been evaluated on different dosing schedules as the majority of trial participants received the second dose within the window specified in the study design,” the Pfizer/BioNTech statement says. “There is no data to demonstrate that protection after the first dose is sustained after 21 days.”
Although it is true that no COVID-19 vaccine clinical trial investigating two-dose regimes can report clear data on the long-term protection generated by one dose, not all experts are against the idea of delaying the second dose. Stephen Evans, from the London School of Hygiene and Tropical Medicine, says the UK is currently in a crisis scenario due to its current wave of infections, and this factor must be taken into account when considering vaccine scheduling decisions.
“The trials did not compare different dose spacing or compare one versus two doses, so we simply do not know what is ‘optimal’,” says Evans. “So, the information directly from the trials is lacking. We have to utilize what we know from science generally. We know that vaccinating only half of a vulnerable population will lead to a notable increase in cases of COVID, with all which that entails including deaths. When resources of doses and people to vaccinate are limited, then vaccinating more people with potentially less efficacy is demonstrably better than a fuller efficacy in only half.”
A trio of new articles published in the Annals of Internal Medicine all argue that single doses administered to many could be more effective at reversing infection rates in the short term. One analysis, from a team of Harvard and Yale researchers modeling the impact of one-dose vaccination schedules compared to two-dose schedules, concludes the US should at least consider one-dose vaccine candidates.
“Depending on the duration of protection conferred – and, of note, considering only a six-month time horizon – a single-dose vaccine with 55 percent effectiveness may confer greater population benefit than a 95 percent-effective vaccine requiring two doses,” the new research notes. “This suggests that now that a highly effective, two-dose vaccine for COVID-19 has been authorized and vaccination programs have begun, sustained and aggressive investment in pursuit of faster-acting, more convenient, one-dose vaccine candidates remains justified.”
So what's the harm in delaying the second vaccine dose? Paul Bieniasz, a virologist from Rockefeller University, expressed perhaps the biggest concern regarding the UK decision to change its vaccination schedule. Bieniasz described delaying the time between a first and second vaccine dose as the perfect way to “generate vaccine-resistant SARS-CoV-2 variants.”
“Generating a pool of hosts with just the right amount of neutralizing antibody to apply selection pressure, but also maintain sufficient levels of partially antibody-resistant virus to allow onward transmission is key here,” writes Bieniasz in a Twitter post entitled Musings of an anonymous, pissed off virologist. "We might not achieve this shortly after the first dose, but if we let immunity wane for a little while, say 4 to 12 weeks, we just might hit the sweet spot.”
Florian Krammer, a microbiologist from Mount Sinai, echoes Bieniasz concerns. Krammer explains, in laboratory conditions when scientists want to generate virus variants that can escape immune targeting they will subject the virus to low antibody pressures and over time mutant strains will appear that can overcome those antibodies.
“I don't know if 12 weeks is going to be a huge issue, but that time frame should be minimized as much as possible,” Krammer muses. “Also, there are good reasons for giving the second dose. It is likely that the second dose is needed to generate long lived and strong immunity.”