BARCELONA — German Chancellor Angela Merkel did it. So did Canada’s Prime Minister Justin Trudeau and Italian Premier Mario Draghi. They bucked the advice of health agencies and mixed their COVID-19 vaccines after doubts about the effectiveness of the AstraZeneca version against the Delta variant began circulating.
In what appears to be a growing trend across Europe, the three leaders first received a dose of an adenovirus vaccine (AstraZeneca) before switching to an mRNA vaccine for the second. Merkel and Trudeau took Moderna’s COVID jab for their follow-up shot, while Draghi opted for Pfizer, overlooking the advice from agencies like the Centers for Disease Control and Prevention, who warn against treating the vaccines as interchangeable.
Mixing and matching different types of vaccines — an “off-label” practice currently not endorsed by the World Health Organization — is now common practice in Canada and 15 European countries, and has started to gain traction in the U.S., where there is growing concern over whether the Johnson & Johnson vaccine provides robust enough protection for the Delta variant.
Questions abound, however, about the safety and efficacy of this approach.
“We’re in an evidence-vague, murky fog. It’s like a fog of war,” Dr. Eric Feigl-Ding, a senior fellow at the Federation of American Scientists, told Yahoo News.
Former WHO director of crisis management Daniel López-Acuña, who is based in Spain, a country that has led the practice of mixing vaccines, agreed that there is too little evidence to show whether the practice makes sense.
“We need to accept that we are in a gray area from the perspective of the evidence necessary to make a sound decision,” López-Acuña told Yahoo News.
On Thursday, the controversial practice got a proverbial shot in the arm when the European Centre for Disease Prevention and Control (ECDC) released a report that found that mixing doses could generate a “robust response” against COVID-19.
“Evidence from studies on heterologous (‘mix and match’) vaccination suggests that the combination of [AstraZeneca] and mRNA vaccines induces a robust [antibody] response against SARS-CoV-2 and elicits a higher T-cell response than homologous combinationsm,” the report stated.
“There is a good immune response to such combinations,” Karam Adel Ali, a policy expert on communicable diseases at ECDC, told Yahoo News, adding that while the combination may produce more side effects, “the mix-and-match schedules appear to be generally well tolerated.”
According to the report, other recent studies and the government of Germany, the combo may even be superior at boosting immunity than two doses of the same drug, particularly AstraZeneca, which preliminary research suggests is less effective than mRNA vaccines in fighting off the Delta and Beta variants.
The growing popularity of mix-and-matching vaccines is worrisome to some public health officials. “It's a little bit of a dangerous trend here where people are in a data-free, evidence-free zone as far as mix-and-match,” Dr. Soumya Swaminathan, WHO’s chief scientist, noted during an online press conference last week, before clarifying via tweet hours later that she was referring to individuals, not health agencies.
The WHO does not widely support the mixing of different vaccines except when supplies of the first vaccine are not available.
“For best protection, WHO recommends that both doses of a two-dose regimen be administered, at the recommended intervals,” Dr. Siddhartha Datta, program manager of the vaccine-preventable diseases and immunization program at WHO Europe, told Yahoo News, adding that “WHO recommends that the same product be used for both doses.”
Even Pfizer is wary of the mixed approach, as noted in its media office’s written response to Yahoo News. “Interchangeability is not part of the current regulatory authorizations for the [Pfizer-BioNTech] vaccine. As a biopharmaceutical company working in a highly regulated industry, our position is supported by the label and indication agreed upon with regulators and informed by data from our Phase 3 study,” the company said in an emailed statement. “Therefore we are not currently in a position to support mixed schedules.”
But countries that initially relied heavily on AstraZeneca’s adenovirus vaccine (such as Canada, where a quarter of the vaccinated citizenry received two different types of shots) point to several recent studies, one in Spain and another in the U.K., that showed beneficial results.
For López-Acuña, all vaccines tend to be less effective against the new variants, particularly when someone has received only the first shot of a two-shot vaccine. A recent study published in the New England Journal of Medicine showed that one shot of AstraZeneca was only 30 percent effective in protecting against the highly contagious Delta variant, while Pfizer was 36 percent. (With two doses, the Pfizer vaccine showed efficacy of 88 percent against Delta, while AstraZeneca showed 67 percent.)
“We need to continue vaccinating and completing the schedule of those who have only one vaccine,” he said, adding that countries such as Spain, where Delta is exploding, need to keep curfews and measures like shutting down nightclubs in place.
Feigl-Ding, however, is open to at least considering the viability of mixing vaccines. “The WHO chief scientist doesn't really like [mixing vaccines] because it’s like we’re in a zero-evidence world. But in certain ways, lots of things are in a zero-evidence world. You know, we don’t have a randomized trial for parachute wearing and prevention of deaths. It just makes sense that parachutes slow you down and they prevent it.”
Richard Carpiano, a professor of public policy at the University of California, Riverside, told Yahoo News that he understands how uncertainty can be mistaken for flakiness.
“We look to scientists and clinicians to give definitive answers. But that’s not how a lot of normal science works. Because of a continually evolving situation for a coronavirus that we knew little about just a year ago, the scientific community is moving quickly to understand it and guidelines are frequently being updated. This is actually science working as it should,” he said. “However, to many of the general public, this continual updating risks being viewed as science and public health officials not knowing what they are doing.”
Also unclear, Feigl-Ding said, is the efficacy of mixing with the J&J vaccine, which non-peer-reviewed findings suggest is also far less effective than the mRNA jabs against variants of COVID-19.
For Dr. Peter Hotez, a vaccine scientist at Baylor College of Medicine, the biggest issue is getting everybody fully vaccinated — including people in poorer regions of the world such as Africa, where only 1 percent or so of the population has been fully inoculated against COVID.
“No vaccine is perfect,” he told Yahoo News. “But I think we will be able to vaccinate our way out of this. I think we’ll likely need a third immunization to do it, at some point, but I do think if we can get enough people vaccinated, I think we can vaccinate our way out of this epidemic.”
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