Thread by @Daniel_E_Park

Preprint: Higher IgG4 is linked with lower neutralizing Ab & Fc receptor responses. Paper also suggests the Novavax platform may produce higher IgG1/3 and lower IgG4 compared with mRNA COVID vaccines.

To illustrate the magnitude:
NVX priming vs. mRNA priming = 49 vs 8,567 ng/mL in IgG4 (the bad one).
Conversely, IgG1 - 3 (the good ones) were similar or higher in the NVX group.

Link: medrxiv.org/content/10.110…

NVX also appears to have beneficial characteristics for protecting against newer variants due to:
1. less immune imprinting
2. enhanced Fc effector functions (that are less impacted by variant changes)

On immune imprinting, recent data suggests the vast majority of mRNA responses tend to be towards ancestral strains:

Comparatively, the NVX boost primarily enhanced nAb levels to the newer target variant.cell.com/immunity/fullt…

We had long suspected that Fc effector functions are a main benefit of NVX (~60% of the protection, and less impacted by variants).
The preprint shows strong negative correlations between IgG4 and Fc effector functions.
This may help explain why NVX has strong Fc protection

This is a preprint so it needs to undergo peer review. But may fill in gaps on how NVX functions and provides similar protection to mRNA despite comparatively lower absolute IgG levels (e.g. produces less bad IgG, more good IgG).