France to offer mRNA jabs as second dose after AstraZeneca 

France has become the second country after Germany to recommend that younger people who have had a first dose of the Oxford/AstraZeneca vaccine be given a different jab for their follow-up shot.

The mixed-dose approach has been recommended by health experts in both countries — despite there being little clinical trial data to support it — because of the slim risk that younger people can develop blood clots when given the AstraZeneca jab.

The World Health Organization reiterated its position on Friday that there was “no data on interchangeability of vaccine platforms”, noting further research was needed.

The move comes as the European Medicines Agency said it is also probing a possible link between the Johnson & Johnson vaccine and four serious cases of unusual blood clots in the US, where it is currently being rolled out. It is not yet being distributed in the EU or UK. The vaccine is based on an adenovirus vector, similar to the AstraZeneca shot.

The EMA said it was not yet clear whether there was a causal link. J&J said it is working with experts and regulators to assess the data. “Our close tracking of side effects has revealed a small number of very rare events following vaccination,” it said. “At present, no clear causal relationship has been established.” 

In France, the policy will affect roughly 530,000 people under age 55 who were given a first shot of AstraZeneca from early February to mid-March when they were eligible under its strategy of giving healthcare workers the vaccine, while reserving the mRNA vaccines for elderly people most at risk.

The Haute Autorité de Santé, a panel of medical experts which advises the government, has said they should be given booster shots from BioNTech/Pfizer or Moderna. France has changed course to use AstraZeneca only in people aged above 55 since the blood clot issue emerged.

France announced its decision on Friday after the HAS recommended the mixed-dose strategy. Germany took a similar stance in early April. 

Health minister Olivier Véran told RTL radio on Friday that the mixed-dose approach was “totally logical” given the analysis of European regulators and France’s desire to continue its vaccination campaign as the scientific evidence evolved.

European countries, whose vaccination campaigns have been slower than world leaders such as the US, Israel, and the UK, have been grappling with how to use AstraZeneca doses since the blood clot reports emerged, with some countries applying new age restrictions and others pausing its use entirely.

But with Covid-19 still spreading, officials are also seeking to reassure people that the AstraZeneca vaccine’s benefits still largely outweigh the risks. 

The European Medicines Agency recently established that there was a “possible link” between the AstraZeneca vaccine and unusual blood clots with low blood platelets that have mostly affected women under 60 years old, though regulators have said there is no specific risk factor by gender.

The EMA said it had examined at least 86 such reported cases and 16 deaths, and recommended updating the vaccine’s safety information to list the clots as a possible side effect.

Élisabeth Bouvet, a vaccine expert and member of the HAS, said on Friday that the mixed-dose approach was a practical solution intended to protect younger people, who are at lower risk of developing severe forms of Covid-19, from the risk of blood clotting side effects. “It is really a choice based on safety,” she said.

“Given that the protection of the Covid-19 vaccines begins to diminish after three months, these people need an additional dose,” she added. “The idea is to give mRNA vaccine as a second dose for this population in a ‘prime-boost’ strategy.”

Even in the absence of clinical data, Bouvet said that they believed the approach carried low risks of side effects and was likely to offer people additional protection given that the Covid-19 vaccines all aim at the same spike protein on the coronavirus.

“We think that this approach will work,” she said. “There is no reason to expect any particular side effects with mixed dosing but it would be good to study the immune response it creates.” 

Peter English, a retired Public Health England consultant in communicable disease control, said it was “reasonable” to use other vaccines, particularly in younger patients, until the risk of blood clots caused by the AstraZeneca vaccine has been clarified.

“If we are to achieve vaccine-induced herd immunity [not just through masks and social distancing] a high uptake of vaccination will be required in the groups most likely to spread the virus, not just in those most at risk if infected,” he said, noting vaccine mixing and matching has been done for other diseases. 

Trials studying a combination of vaccines, including AstraZeneca’s and Russia’s Sputnik V shots, are under way.