While mix-and-match sounds more like a meal deal at your local fast-food chain, it’s now the colloquial term being used for the approach currently under study in the U.K. for administering two doses of different types of COVID-19 vaccines.
While mix-and-match sounds more like a meal deal at your local fast-food chain, it’s now the colloquial term being used for the approach currently under study in the U.K. for administering two doses of different types of COVID-19 vaccines.
Current emergency use approval for coronavirus vaccines in the U.S. is for two shots from the Pfizer-BioNTech vaccine, two shots from Moderna or one from Johnson and Johnson. Researchers believe that combining a viral vector vaccine with an mRNA vaccine would not only help with vaccine supply issues, but also boost vaccine response.
The combination of vaccines to fight one pathogen is known as a heterologous prime-boost. This approach was approved last year by European regulators to protect against Ebola. It’s also been deployed in studies for diseases like HIV, malaria, TB and influenza.
“In the U.K. at the moment, we’re sort of calling it ‘mix and match,’ ” says Helen Fletcher, a professor of immunology at the London School of Hygiene & Tropical Medicine. "...there’s a practical reason why you would want to mix two different types of vaccine. But there is also a scientific reason as well.”
Vaccines train the recipient’s immune system to recognize a particular invading virus, similar to showing an assassin a picture of their target. Administering two different types of vaccines would give two pictures of the virus, like a headshot and profile.
The current recommendation by health agencies in France and Germany are for individuals who’ve already gotten the AstraZeneca vaccine to consider getting one of the mRNA vaccines for a second shot. The viral vector vaccine stimulates a good T cell response, while the mRNA vaccine creates a solid antibody response. Combining those immune responses should potentially give the best protection.
“If you give two different types of vaccine, then you tend to get a better immune response than if you give the same vaccine twice,” Fletcher says.
Researchers believe that combining two vaccines will harness the best features of each, particularly for fighting the variants that will continue to emerge. But they don’t yet have the data to prove it.
A trial in Oxford launched in February enrolled over 800 people to test two dosing schedules: one with four weeks between the two jabs, and the other with 12 weeks between doses. Initial data is expected this June to evaluate safety concerns and measure levels of antibodies and T cells participants produce after their “mix and match” immunizations. Animal studies published in January showed a better CD8 T cell response in mice from the combination approach over either RNA or AstraZeneca vaccine alone.
Another benefit to mixing vaccine types is to avoid the body building an immunity against the modified virus used to deliver the vaccine. There’s no health risk to it, but if they immune system develops a response to the viral platform delivering the coronavirus spike protein, instead of the protein itself, it would dampen the immune response to COVID-19.
“If you mix different types of vaccine, we can imagine that you will increase the (immune) response against the common antigen which is the antigen of interest and not against the vector itself,” said Dr. Frédéric Martinon an immunologist at the French National Institute of Health and Medical Research.
A few vaccine manufacturers have run with this approach and are developing two different types of vaccines to utilize the combination strategy. Gritstone bio, out of Emeryville, California, is working on a viral vector vaccine and an mRNA vaccine.
“The natural human response to a virus is to mobilize two distinct arms of the immune system,” says Gritstone CEO Andrew Allen.
After the viral vector stimulates the production of CD8 T cells, Allen said, “The mRNA [vaccine] makes a really good antibody response. And so potentially by combining these, you kind of get the best of both worlds.”
Testing for the company’s dual vaccine approach is already underway in humans.