RNA vaccines appear to produce very different levels of antibodies

We have tended to treat RNA-based vaccines from Moderna and Pfizer / BioNTech as functionally equivalent. They take an identical approach to producing immunity and have a very similar set of ingredients. Data from clinical trials suggested that they had very similar efficacy, both in the 95 percent area.

So it was a bit of a surprise to see an article published yesterday indicating that the two produce an easily distinguishable antibody response, with Moderna inducing antibody levels more than double those seen in people who received the Pfizer / BioNTech vaccine. . While it is important not to infer too much from a single study, it was large enough that the results were likely to be reliable. If so, the results serve as a warning that we might not want to base too much of our expectations on relatively crude measurements of antibody levels.

The new study

The work itself was remarkably simple. A Belgian medical center was vaccinating its staff and asked for volunteers ready to donate blood samples. Samples were taken both before vaccination and six to 10 weeks after, with the levels of specific antibodies to the SARS-CoV-2 spike protein tested at the colon. About 700 participants received the Moderna vaccine, while about 950 received the Pfizer / BioNTech vaccine.

With the data in hand, the researchers simply compared the levels of antispike antibodies in the different groups. One thing this revealed is that those who had been infected before the vaccination developed a much higher response than the other participants, with more than five times the amount of antibodies after the vaccination.

But the notable surprise was that the Moderna vaccine generated a stronger response than the Pfizer / BioNTech version. In terms of units of antibody per milliliter of blood sample, the difference was 3,836 to 1,444, with non-overlapping confidence intervals. In other words, it is a statistically significant difference in a sample large enough that it is unlikely to be by chance.

That said, there are a few caveats. The first is that while the medical center was probably able to store and administer vaccines appropriately, it was at the end of a complicated production and distribution network, and it is possible that something was arrived at one of the vaccines before it reached its destination. the clinic. A simple replication would fix this quickly.

What to do with it?

The other important caveat is that the researchers behind the study simply measured the total levels of antibodies stuck to the spike protein. Only a subset of these will be so-called neutralizing antibodies, which adhere to the tips in a way that interferes with the protein’s ability to interact with cells and insert the virus genome. Measuring neutralizing antibodies is much more difficult, so most studies do what this one has.

But it’s technically possible that despite the differences in total antibodies, the two vaccines generated similar levels of neutralizing antibodies, something else that further study may resolve. This would be consistent with the generally similar levels of protection of vaccines, as protection appears to be correlate with neutralizing antibody levels.

While we wait for data to help us sort out this problem, it is worth asking whether we are not putting too much emphasis on antibody levels in our decision making. Part of the argument at the present time for the need for boosters is that antibody levels decline over time, although this is a normal consequence of moving from a response to a active infection to a functional immune memory of this infection. And part of the effectiveness of a booster is that it restores high levels of antibodies, even if that’s exactly what should occur when immune memory cells are activated by re-exposure to the spike protein.

As with these new findings, these findings should be approached with caution, as we do not fully understand how these changes in antibody level correlate with protection.

JAMA, 2021. DOI: 10.1001 / jama.2021.15125 (About DOIs).