Why mix-and-match at all? Part of the thinking among scientists is that by administering different vaccines that expose the immune system to different parts of a pathogen, one after the other, the body becomes trained to recognize different parts of the invader and becomes more effective at defending against it.
Another line of reasoning is that using different kinds of vaccines jump-starts different elements of the immune system. Viral vector vaccines, for example, are well-equipped to stimulate a part of the immune response that helps generate an army of what are called “killer T cells” to protect the body against an invading virus. Other kinds of vaccines are thought to skew more heavily toward prompting the creation of antibodies to combat the virus. Both immune system responses are helpful, and scientists’ theory is that combining them could be more potent than either of them alone.
One area where the mix-and-match approach stirs the most hope is in the fight against H.I.V., where vaccine researchers have been investigating it for decades. In what might have been the first human trial of this method, the immunologist Dr. Daniel Zagury of the Pierre and Marie Curie University in Paris received two different experimental H.I.V. shots in 1987. First, a version of a virus that was engineered to produce an H.I.V. protein in the body, and later booster shots of the protein directly (rather than the engineered virus). Dr. Zagury and his colleagues reported that his immune system showed signs of responding, including producing antibodies.
Although attempts at making a successful H.I.V. vaccine have faltered since then, there is still enthusiasm for the mix-and-match approach. A trial called RV144, done more than a decade ago, followed the mix-and-match approach and was the only H.IV. vaccine trial to ever show protection against the virus among a handful of other experimental H.I.V. vaccines. More trials of this kind are underway, and the hope is that finding the right pairing of vaccines will prove successful.
It’s clear that many Covid-19 vaccines are mightily effective on their own and don’t need to be paired with other versions. But scientists should keep a close eye on the results of the mix-and-match trials underway to see if large, well-controlled studies show any signal of better protection.
The findings could inform vaccine development for other pathogens. This is especially true for viruses that mutate even more rapidly than SARS-CoV-2, like H.I.V. In an era of multiplying vaccine technologies, it might be the case that vaccines, like people, prove more effective when they work together.
Roxanne Khamsi is a science journalist covering Covid-19.
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