Thread by @BalazsLab

As we wait for medRxiv, I wanted to share our complete results in a new thread. I want to stress that this is still a pre-print that has not yet undergone peer review. Many thanks again to @wilfredo_nk @EvanCLam @kstdenis29 and @NaranbhaiVivek for all of their hard work!

To test the potential for both the Pfizer and Moderna vaccines to produce serum responses capable of neutralizing circulating #SARSCoV2 variants, we built a series of spike-expression plasmids:

The details of the mutations we made and a comparison between the strains can be seen in this figure:

We used these plasmids to produce pseudovirus bearing each of these spike proteins and mixed them with the sera we had collected from participants. These were mostly younger individuals (22-42yo) who had received one or two doses of either #PfizerBioNTech or #Moderna vaccine:

As I shared previously, the data from recipients of the Pfizer vaccine showed a significantly reduced ability to neutralize P.1/P.2 and B.1.351 lineage pseudoviruses:

We saw similar results with sera from recipients of the Moderna vaccine, however we had few samples from people who had received both doses:

Given that we had more people who had received both doses of the Pfizer vaccine, we summarized the relative neutralization differences we saw for this group:

To ensure that differences in spike expression were not responsible for the differences we were observing, we measured spike at the cell surface and saw fairly consistent signal, suggesting that this was not likely the reason for the differences we saw in neutralization potency:

Given that B.1.351 showed the greatest differences, we mapped where these mutations were on the spike and divided them into receptor binding domain (RBD) or non-RBD.

To better understand what was driving B.1.351 escape, we produced pseudoviruses with spike proteins that had the three RBD mutations reverted to their wildtype sequences and re-tested these against the sera from people receiving two-doses of Pfizer vaccine:

We found that a significant fraction (but not all) of the escape that we measured could be explained by the three RBD mutations. This suggests that the sequence context in which these RBD mutations are found also contributes to escape from serum neutralization.

If anyone is interested in reading the complete pre-print, it is now available for download on out lab's website: balazslab.partners.org

The pre-print is now available through medrXiv:
medrxiv.org/content/10.110…