As more COVID-19 vaccines become available, researchers are testing the impact of linking different products that require two shots.
Beata Zawrzel / NurPhoto via Getty Images
By Jon Cohen
Science‘COVID-19 reporting is supported by the Heising-Simons Foundation.
With nine vaccines now showing that they can potentially prevent serious illnesses and deaths due to COVID-19 – and vaccine shortages – researchers are investigating an issue that was only hypothetical even a few months ago: would people need vaccines that require two, mix and match? shots?
If some combinations work, it can provide the necessary flexibility when the production of a vaccine fluctuates, as often happens. And there is even a chance that doses of two different vaccines could increase COVID-19 protection.
Related
One mixed vaccine trial is already underway: it is investigating a dose of Sputnik V vaccine made by the Russian Gamaleya Research Institute for Epidemiology and Microbiology at a booster dose of a similar vaccine given by AstraZeneca and the University of Oxford. A second trial, which examines a combination of the AstraZeneca-Oxford and Pfizer-BioNTech vaccines, which mix two different technologies, is just underway, and others are being discussed.
Until these trials yield results, however, health officials are asking for caution. The U.S. Centers for Disease Control and Prevention has advised people against mixing vaccines unless there are ‘exceptional situations’, such as a shortage of the vaccine they first received due to production or distribution hiccups. In the United Kingdom, Public Health England has taken a similar position.
But the scarcity of COVID-19 vaccines – and the urgency to increase vaccination rates – bring the mix-and-match problem to the fore. “As we have more interchangeable products, it will have a huge impact on the implementation of this mass vaccination campaign in the environment of uncertain inventory,” said Bruce Gellin, head of global vaccination for the nonprofit Sabin Vaccine Institute.
“There are definite benefits to having data that can support a more flexible vaccination program, if necessary and if approved by the medicine regulator,” said Jonathan Van-Tam, the UK’s deputy chief executive, in the announcement of the trial in which the AstraZeneca Vaccines against Oxford and Pfizer-BioNTech.
Researchers have previous experience with mix-and-match vaccine trials. For more than twenty years, the campaign against HIV vaccines has tried to combine different vaccine strategies to elicit more powerful immune responses, but no one has succeeded. Johnson & Johnson has launched an Ebola vaccine in the European Union that combines its preparation with one that uses a very different formulation manufactured by Bavarian Nordic. To achieve a more robust protection in the elderly, an uptake of a pneumococcal conjugate vaccine is enhanced by one containing a pneumococcal polysaccharide. The inactivated polio vaccine was also given for safety reasons before being made with live attenuated virus, which can sometimes cause the disease if the virus mutates. But there are few other examples of the use of two vaccines approved for the market in a one-two punch.
Mixing and adjusting COVID-19 vaccines can cause several complications. One is regulatory: what if, we say, only one is authorized for emergency use? Another is immunological: some vaccines have the same underlying technology platforms – such as the messenger RNA technology used by the Pfizer-BioNTech collaboration and Moderna – but others do not.
On the other hand, different platforms of the immune system can be turned on. And when paired platforms are linked, it can evade unwanted immune responses. For example, both Gamaleya’s Sputnik V vaccine and the AstraZeneca-Oxford vaccine use different adenovirus (Ad) vectors to deliver a key gene to human cells. Both require a first recording, followed by an amplifier. The Lancet published efficacy data for each vaccine, and they received permits for emergency use in several countries.
Gamaleya uses two different Ad vectors that contain the spike gene for its priming and booster shots: Ad26 followed by Ad5. AstraZeneca and Oxford use the same chimpanzee adenovirus (ChAd) for both its primary and booster. In theory, using the same vector for both shots by AstraZeneca means that the immune response caused by the first shot can paralyze the booster. This possible problem can be avoided by combining the AstraZeneca shot with the Sputnik V-one, presumably in any order.
Gamaleya, in turn, could benefit from using the AstraZeneca-Oxford vaccine as a stimulant because, according to a Bloomberg report, the institute had difficulty making the Ad5 vector. (Sputnik V representatives said Science they did not comment on the Bloomberg report, but said that delays in supplies to Latin America could occur as they upgraded production facilities.) And many researchers criticized Gamaleya for choosing Ad5 due to disastrous trials in 2007 with An Ad5-based HIV vaccine that somehow increased the risk of infection with the AIDS virus. So an Ad26-ChAd combination comes out of that concern.
Sputnik V’s financial backers also contacted CanSino Biologics, a Chinese company that makes an Ad5 single-shot vaccine to link their vaccinations, CEO Yu Xuefeng said. Science. But they have not yet negotiated an agreement. CanSino did not report effectiveness data. A Pakistani prime minister’s health adviser tweeted on February 8 that the CanSino candidate had worked 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 believe it is accurate.)
The UK National Immunization Schedule Consortium is moving forward with an extensive mix-and-match study of the AstraZeneca-Oxford and Pfizer-BioNTech vaccines. It has eight different strategies in which the vaccines must be given in different order and at different intervals. Van-Tam hopes the trial will “provide greater insight into how we can use vaccines to stay abreast of this nasty disease.”
Gellin is frustrated for the first time because more mix-and-match trials are not already underway. “It should be a top priority for someone,” he says. But Gellin admits the regulatory issues are frightening. “This is something companies need to do, and maybe they will be able to do it,” he says. “But they will probably need more lawyers than volunteers.”