UK Delay of Second COVID-19 Vaccine Dose – A Risky Strategy That Could Give Rise To More Virus Mutations, Some Experts Warn
The administration of the Pfizer COVID-19 vaccine in mid-December.

The United Kingdom’s decision to delay the second dose of the Pfizer/BioNTech COVID-19 vaccine being rolled out en masse in the nation is a risky strategy – not only for those getting the vaccine, but also in terms of the longer-term public health impacts such delays could have in terms of future SARS-CoV2 mutations, some experts are warning. 

Administering a weakened vaccine formulation, as a result of long delays between the required two vaccine doses could open the door for the more rapid evolution of SARS-CoV virus, including mutations resistant to the vaccines only just now being deployed en masse, several leading virologists have said.  

They spoke in the wake of Britain’s decision on 30 December to postpone the administration of the second dose of the two-dose Pfizer vaccine by as much as 4 to 12 weeks, so that more first doses could be administered right away. 

Delaying the second dose has the potential to generate resistant spike variants that evade the antibody responses induced by vaccines, tweeted Paul Bieniasz, a British-American virologist at Rockefeller University. 

“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…If we let immunity wane for a little while, say 4 to 12 weeks, we just might hit the sweet spot” to generate vaccine-resistant SARS-CoV2 variants, Bieniasz added. 

While the UK’s novel attempt to provide some form of broad population immunity as fast as possible is laudable, the experts says, potential negative impacts on the mutation of the virus, and thus on vaccine effectiveness, could offset the benefits. 

“The most credible arguments…are: a) the possibility that ‘partial immunity’ will spawn harmful mutations; b) concern that delay means more people won’t return for 2nd dose; c) whether change in vaccine schedule will lead to more vaccine hesitancy,” said Bob Wachter, chair of the Department of Medicine at University of California at San Francisco, in another series of Tweets

UK Was First In Pfizer Rollout – But Stretched Resources Leave It Hunting For More Doses

The United Kingdom was the first country in the West to issue an emergency authorization for the Pfizer vaccine, followed by the launch of the mass vaccination campaign on 8 December, beginning with health workers and older people. So far, the vaccine has been administered to about 1 million people nation-wide through the National Health Service, with second shots due three weeks later.

The total number of doses of COVID-19 vaccines administered globally, as of January 4.

The decision to prioritize the administration of the first dose to as many at-risk individuals as possible over providing the two doses according to the recommended schedule was made amid the spread of a variant strain of SARS-CoV2 with a higher rate of transmission and higher viral load. 

These measures were justified as “allow[ing] more people to benefit from the protection provided from the first dose during the roll out phase,” states the updated UK guidelines “Greenbook.”  An accompanying statement by the Joint Committee on Vaccination and Immunisation (JCVI), makes the case, saying that in the case of the Pfizer vaccine, vaccine efficiency would still be at least 70% and possibly as high as 90%, from about two weeks after the first dose, based on models of the clinical trials undertaken so far.    

But with the absence of clear data on the length that protection from the first dose lasts, Britain’s decision could have dangerous ramifications, leaving millions of people with incomplete or waning immunity, other independent experts pointed out. 

“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,” tweeted Florian Krammer, professor at the Department of Microbiology at the Icahn School of Medicine at Mount Sinai in New York City. “But it will likely also drive affinity maturation of antibodies. This will make the antibodies stronger, and potentially will allow them to better cope with new variants.” 

Moncef Slaoui, head of the US Government’s Operation Warp Speed rollout of COVID vaccines in the US, also criticized Britain’s decision in an interview with CBS “Face the Nation,” saying: “We always said that these vaccines would be developed on the basis of science and all decisions would be made transparently on the basis of data. Changing the decisions made…which was to give two doses of vaccine – the second dose gives you ten times higher immune response than the first – without any data, I think would not be responsible.” 

Meanwhile, Pfizer and BioNTech warned in a joint statement released on Monday that “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.”

Mixing and Matching Of Vaccines also Emerges as an Issue

Last week British regulators also became the first to approve a vaccine developed by AstraZeneca and Oxford University, which is also a two dose regimen – based on a more conventional adenovirus vector technology, and also more temperature resilient than the sensitive Pfizer mRNA vaccine, which requires ultra cold storage.   

British regulators have also suggested that they might allow for the mixing of different vaccine brands, as well, in some situations. According to the UK’s updated vaccination guidelines, in cases “where the same vaccine is not available, or if the first product received is unknown, it is reasonable to offer one dose of the locally available product to complete the schedule.” 

But while the guidelines offer vaccine mixing and matching as an option, this should only take place on very rare occasions and “every effort should be made to give [the patient] the same vaccine,” stressed Mary Ramsay, head of immunizations at Public Health England.  

The US media, meanwhile, has overplayed the impacts of the “mix and match” vaccine option as a part of UK vaccine strategy, Fiona Godlee, editor of The BMJ was reported to have said in a letter to the New York Times. Godlee stressed that the strategy was not a recommendation, but rather a strategy of last resort, the BBC reported. Godlee demanded that the New York Times print a correction to its previous article, which had stated that: “Britain Opens Door to Mix-and-Match vaccinations, Worrying Experts”.

Image Credits: Flickr – Province of British Columbia, Our World in Data.

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