On December 30, the Medicines and Healthcare products Regulatory Agency (MHRA) approved the ChAdOx1 nCoV-19 vaccine – developed by the University of Oxford and AstraZeneca – for use in the UK. It is the second COVID-19 vaccine to be approved for use in the UK after Pfizer/BioNTech's BNT162b2 received authorization on December 2.
The announcement and subsequent rollout of ChAdOx1 has been greeted with excitement, and the two vaccines were described as a prospect of hope when Prime Minister Boris Johnson declared the need for a third nation-wide lockdown on January 5.
However, in the statement announcing ChAdOx1's approval, the MHRA also declared a change to the vaccine dosing schedule in the UK. Both ChAdOx1 and BNT162b2 will now be administered as one injection followed by a second dose injected up to 12 weeks later. This regimen has not been tested in a clinical trial.
Why has this change been made?
The change to the regimen has been attributed to the worsening situation in the UK, where 391,615 individuals have tested positive in the last seven days. By altering the regimen, the government hopes to increase the speed at which the vaccine can be distributed, ensuring that as many people as possible receive the first dose.
"It remains critical that groups most at risk, such as the elderly and frontline healthcare and essential workers, are prioritized to receive the first doses, but we must not delay getting the vaccine to everyone, in this country and around the world. The dosing regimen announced today will allow a more rapid rollout," said Sir Jeremy Farrar, director of Wellcome.
What is the MHRA?The MHRA is the execute agency of the Department of Health and Social Care in the UK. It is responsible for ensuring that medicines, medical devices and blood components meet the required standards of safety, quality and efficacy.
"The Joint Committee on Vaccination and Immunisation (JCVI) has advised the priority should be to give as many people in at-risk groups their first dose, rather than providing the required two doses in as short a time as possible," the UK government said. It emphasizes that each individual will still receive their second dose, which will complete the course.
The UK faces an unprecedented situation
As has commonly been the case with public health decisions throughout the global pandemic, there are divided opinions as to whether this choice was the right one.
The British Society for Immunology shared a statement where it placed priority on ensuring the COVID-19 vaccines are rolled out in a "manner that maximizes safety and protection", but also recognized that the "UK faces an unprecedented situation".
"We are aware of the speed at which the new variant is spreading in UK (60,000 new infections daily, with nearly 600 daily deaths on average). In this situation would one want to vaccinate a few thousand with two shots or millions with the first shot? Everyone is seeking evidence," – Farooq A Wandroo, consultant hematologist at Sanwell and West Birmingham Hospitals, wrote in a letter to the British Medical Journal.
"Given this, although we would prefer the original dosing schedules tested in the trials to be used clinically, we recognize that a pragmatic approach in the short-term is needed, and accept the rationale for the change in dosing schedule for the Oxford/AstraZeneca and for the Pfizer/BioNTech vaccine that has been recommended by the JCVI," it said.
Ashish K. Jha, professor of global health at Harvard T.H. Chan School of Public Health echoed this viewpoint: "Bottom line is that I realize we are pushing for something that has risk. But we should not ignore the risk of not doing this at all." He describes the evolution of his thinking in a recent Twitter thread.
Counterproductive to public health?
Evidently there are clinicians and research scientists that support the decision as a rational response to the climbing number of cases in the UK. However, others are not convinced.
The British Medical Association (BMA) has branded the decision "grossly unfair" to patients and healthcare professionals across the UK, as the regimen change resulted in the rescheduling of thousands of appointments this week. "The decision to ask GPs, at such short notice, to rebook patients for three months, hence, will also cause huge logistical problems for almost all vaccination sites and practices." Richard Vautrey, chair of the BMA GP Committee, said. He estimated that contacting two thousand elderly or vulnerable patients will require five staff members and would require approximately one week.
In an open letter to Matt Hancock, the Secretary of State for Health and Social Care,, the Doctor's Association UK discusses "grave" concerns and share a statement from Pfizer/BioNTech that confirms there is no clinical trial data supporting the alternative dose regiment for the BNT162b2 vaccine: "Data from the Phase III study demonstrated that, although partial protection from the vaccine appears to begin as early as 12 days after the first dose, two doses of the vaccine are required to provide the maximum protection against the disease, a vaccine efficacy of 95%. There are no data to demonstrate that protection after the first dose is sustained after 21 days."
"Without appropriate data supporting such changes in vaccine administration, we run a significant risk of placing public health at risk, undermining the historic vaccination efforts to protect the population from COVID-19," The US Food and Drug Administration (FDA) commented.
It added, "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. However, making such changes that are not supported by adequate scientific evidence may ultimately be counterproductive to public health."
Undermining public trust in vaccines
Vaccine hesitancy is a major potential barrier to the successful implementation of a COVID-19 vaccine rollout. Pfizer and BioNTech are concerned about the potential impact the UK government's decision will have: "Mixed messages and lack of evidence will inevitably lead to undermining the public trust in the vaccine and could negatively impact on uptake."
The US will not follow suit
Ultimately, the decision on alternative regimens for vaccine dosing lies with the health authorities in the UK, not with the pharmaceutical companies behind the vaccine's development. Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Disease told media outlets that that the US will not be following the UK's example and have no intention of extending the time period between the two doses of the currently-approved COVID-19 vaccines.