As more COVID-19 vaccines become available, researchers are testing the impact of pairing different products that require two injections.
Beata Zawrzel / NurPhoto via Getty Images
By Jon Cohen
Sciences COVID-19 reporting is supported by the Heising-Simons Foundation.
Now that nine vaccines show that they can potently prevent serious illnesses and deaths from COVID-19 – and vaccines are scarce – researchers are pondering an issue that, even a few months ago, was only hypothetical: Should people combine and match vaccines for what it takes two. shots?
If some combinations work, they can provide the necessary flexibility when vaccine production fails, as often happens. And there is even a chance that mixing doses of two different vaccines can enhance protection against COVID-19.
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A mixed vaccine trial is already underway: It is investigating matching a dose of the Sputnik V vaccine made by Russia’s Gamaleya Research Institute of Epidemiology and Microbiology with a booster dose of a similar vaccine made by AstraZeneca and the University of Oxford. A second trial, investigating a combination of the AstraZeneca-Oxford and Pfizer-BioNTech vaccines, combining two different technologies, has just begun and others are currently under discussion.
Until these studies yield results, health officials urge caution. The US Centers for Disease Control and Prevention have discouraged people from mixing vaccines unless there are “exceptional situations,” such as a shortage of the vaccine they first received due to problems with production or distribution. In the United Kingdom, Public Health England has taken a similar position.
But the scarcity of COVID-19 vaccines – and the urgency to ramp up vaccination coverage – brings the mix-and-match issue to the fore. “As we have more products that are interchangeable, it will have huge implications for conducting this massive vaccination campaign in an environment of uncertain supplies,” said Bruce Gellin, who leads global immunization for the nonprofit Sabin Vaccine Institute.
“There are clear benefits to having data that could support a more flexible immunization program, if needed and approved by the drug regulatory agency,” said Jonathan Van-Tam, deputy chief medical officer for the United Kingdom, announcing. the trial in which the AstraZeneca was combined. Oxford and Pfizer-BioNTech vaccines.
Researchers have experience with mix-and-match vaccine studies. For more than 20 years, the long-struggling HIV vaccine field has tried to combine several vaccine strategies to elicit more powerful immune responses, but none have succeeded. Johnson & Johnson marketed an Ebola vaccine in the European Union that combines its preparation with a vaccine that uses an entirely different formulation made by Bavarian Nordic. Likewise, to bring about more robust protection in the elderly, an injection of a pneumococcal conjugate vaccine is stimulated by a vaccine containing a pneumococcal polysaccharide. The inactivated polio vaccine is also given for safety reasons before it is made with live attenuated virus, which can sometimes cause the disease if the virus mutates. But there are some other examples of the use of two vaccines that have been approved for the market in a one-two punch.
Combining and matching COVID-19 vaccines has several potential complications. One is regulatory: what if, for example, only one is authorized for emergency use? Another is immunological: While some vaccines share the same underlying technology platforms – such as the messenger RNA technology used by both the Pfizer-BioNTech collaboration and Moderna – others do not.
On the other hand, different platforms can turn on different arms of the immune system. And linked platforms can evade unwanted immune responses. For example, both Gamaleya’s Sputnik V vaccine and AstraZeneca-Oxford vaccine use different adenovirus (Ad) vectors to deliver a key gene to human cells. Both require a first shot followed by a booster. The Lancet has published efficacy data for each vaccine and has received emergency use authorization in several countries.
Gamaleya uses two different Ad vectors containing the spike gene for its priming and booster shots: Ad26 followed by Ad5. AstraZeneca and Oxford use the same chimpanzee adenovirus (ChAd) for both the prime and booster. In theory, using the same vector by AstraZeneca for both images means that the immune response triggered by the first image can paralyze the booster. That potential problem could be avoided by pairing the AstraZeneca shot with the Sputnik V, presumably in either order.
Gamaleya, in turn, could benefit from using the AstraZeneca-Oxford vaccine as a booster, as the institute has had problems creating the Ad5 vector, according to a Bloomberg report. (Sputnik V Science they did not comment on the Bloomberg report, but said delays in delivery to Latin America could occur if they upgrade the manufacturing facilities.) And many researchers have criticized Gamaleya for choosing Ad5 over disastrous 2007 trials with a Ad5-based HIV vaccine that somehow increased the risk of infection with the AIDS virus. So an Ad26-ChAd combination solves that concern.
Sputnik V funders also reached out to CanSino Biologics, a Chinese company that makes an Ad5 spike vaccine to be used as a single injection, to discuss pairing their vaccines, CEO Yu Xuefeng said. ScienceBut they haven’t made a deal yet. CanSino has not reported any efficacy data. (A health adviser to the Pakistani Prime Minister tweeted on Feb. 8 that the CanSino candidate has been working in a trial there and in other countries. Yu said he could not confirm the report because the company did not see the data, but believes it is correct. is.)
The UK National Immunization Schedule Evaluation Consortium continues an extensive mix-and-match study of the AstraZeneca-Oxford and Pfizer-BioNTech vaccines. It has eight different strategies in which the vaccines are administered in different order and at different intervals. Van-Tam hopes the trial “will provide more insight into how we can use vaccines to keep abreast of this nasty disease.”
Gellin, for example, is frustrated that more mix and match trials have not started yet. “It has to be a top priority for someone,” he says. But Gellin admits the regulatory issues are daunting. “This is something that companies should do, and maybe they can,” he says. “But they will probably need more lawyers than volunteers.”