We know more than ever how to use boosters, but still very little about when to use them.
In this week’s episode of Recall Chronicles, the plot picks up. An FDA advisory committee today began a two-day meeting to make recommendations on whether the agency should authorize additional doses of the Johnson & Johnson and Moderna COVID-19 vaccines. (The FDA should still allow, and the CDC should always recommend, any new use of boosters before they are readily available.) Committee members have already voted yes on giving boosters to people over 65. and other high-risk adults who received the Moderna vaccine. Meanwhile, the NIH released the results of a long-awaited (and not yet peer-reviewed) clinical trial of the “mix and match” approach to booster injections, in which people are given a dose of one. different vaccine than the one they started with. . The FDA committee is also expected to discuss this idea before the end of this meeting.
The 458 people NIH study has shown that the mix-and-match, also known as heterologous– the booster is safe and induces an increase in the number of relevant antibodies, regardless of the combination of vaccines. This is not particularly surprising, given the data that has already emerged from countries such as the UK. and Spain, who have been studying the mix-and-match approach to initial fire patterns for months. In general, these have been shown to be about as good, and in some cases better, than a counterpart diet. This week’s report expands on that finding for the age of the boosters and adds another: When the boosters were compared one-on-one, the mRNA vaccines blew the J&J out of the water.
When vaccines debuted last winter, Americans were told that each was excellent, so we should all pick whichever of the three was the most accessible. If mix-and-match boosters are allowed, we might end up with a more bewildering decision: nine different paths will be available in total, depending on where you started. Assuming all options are on the table soon, which one should people choose?
The NIH study tested and compared every possible combination, and here’s the bottom line: If you need a booster, don’t take J&J. Two weeks after the booster, people who had followed a J&J → Moderna regimen recorded mean antibody levels 9.8 times higher than those who had received two injections of J&J; antibody levels in J&J → Pfizer recipients hovered just behind. Overall, the highest antibody levels were found in people for whom all three doses were Moderna; Pfizer → Moderna produced the second highest levels, then Moderna → Pfizer.
Moderna’s boosters seemed slightly more effective than Pfizer’s in general, but that doesn’t mean Americans who have ever received Pfizer boosters are missing out on anything. The differences between these mRNA regimes were relatively small; more precisely, they are absolutely overshadowed by the differences between either mRNA option and the J&J → J&J approach. Saad Omer, who heads the Institute for Global Health at Yale, told me that “we can’t be too specific” in interpreting this data, given the small size of the study. (There were only about 50 people in each of the nine test groups.) But the apparent advantage of using mRNA vaccines as boosters, over J&J’s, is so significant, has t he says it is unlikely to be a mistake.
Other factors could also limit the size of the apparent Moderna-Pfizer division. In a article published earlier this week, a team including Omer and led by colleague Akiko Iwasaki found that those who have recovered from COVID-19 infection and vaccinated could approach a plateau of immune protection, after which “the juice [of a booster shot] not worth the pressure, ”Omer said. This suggests that the differences between the mixed combinations might be even less significant for this population (although Omer said he would have to consult clinical data to be sure). Moderna’s benefit could also be blunted given today’s committee recommendation for the use of a half-dose booster. (The NIH study tested full-dose boosters of Moderna.) Yet previous research suggests that half a dose of Moderna because the first or second injection were indeed “generally comparable” to the original regimen. “I would be very surprised if it didn’t work very well as a booster,” says Paul Sax, professor at Harvard and clinical director of the division of infectious diseases at Brigham and Women’s Hospital.
All of the results described above may only tell part of the story. Remember, the NIH study used antibody count, which is a proxy measure of actual immunity. Antibodies are the body’s first line of defense against coronavirus, but they’re not our only weapon. Immune cells, such as B and T cells, are also important, especially in the long run. (Sax told me that some researchers believe J&J might be particularly effective in inducing this latter, more lasting form of immunity.) The best way to determine which of the nine mix-and-match options produces the best protection against the disease would be to recruit thousands of volunteers for a randomized controlled trial and then count how many people on each diet get sick over an extended period. But other than that, antibody levels provide the best and most practical information that can be gathered quickly from as many people as possible.
Omer would like to see such long-term data on clinical outcomes, as well as more data on the effects of mix-and-match strategies on different age groups and on the duration of booster protection. These types of data are lacking in many recall studies, not just on the mix-and-match. Until we get them we’ll be stuck where we are right now, knowing more than ever about How? ‘Or’ What boost, but still unsure of when, exactly, it is most appropriate to do so.