Preserved Omicron Spike specific antibody binding and Fc-recognition across COVID-19 vaccine platforms

Abstract

Despite the dramatic spread of Omicron globally, even among highly vaccinated populations, death rates have not increased concomitantly. These data argue that alternative immune mechanisms, beyond neutralization, may continue to confer protection against severe disease. Beyond their ability to bind and block infection, antibodies contribute to control and clearance of multiple infections via their ability to direct antiviral immunity via Fc-effector mechanisms. Thus, here we probed the ability of vaccine induced antibodies, across three COVID-19 vaccines, to drive Fc-effector activity against Omicron. Despite the significant loss of IgM, IgA and IgG binding to the Omicron Receptor Binding Domain (RBD) across BNT162b2, mRNA-1273, and CoronaVac vaccines, stable isotype binding was observed across all of these vaccines to the Omicron Spike. Compromised RBD binding IgG was accompanied by a significant loss of cross RBD-specific antibody Fcγ-receptor binding by the CoronaVac vaccine, but preservation of RBD-specific FcγR2a and Fcγ3a binding across the mRNA vaccines. Conversely, Spike-specific antibodies exhibited persistent binding to Fcγ-receptors, across all three vaccines, albeit higher binding was observed with the mRNA vaccines, marked by a selective preservation of FcγR2a and Fcγ3a binding antibodies. Thus, despite the significant to near complete loss of Omicron neutralization across several vaccine platforms against Omicron, vaccine induced Spike-specific antibodies continue to recognize the virus and recruit Fc-receptors pointing to a persistent capacity for extra-neutralizing antibodies to contribute Omicron disease attenuation.

Figure 1:. Vaccine induced antibody binding to different SARS-CoV-2 variants of concern.

Individuals either received the full dose regimen of the BNT162b2(n = 11), mRNA-1273(n=14), or the aluminum adjuvanted inactivated particle vaccine CoronaVac (n=13). Samples were taken at peak immunogenicity 2 weeks after the last dose. IgM, IgA1 and IgG1 binding titers to D614G (WT), Alpha (B1.117), Beta (B1.351), Delta (B.1.617.2), and Omicron (B1.529) variants of concern receptor binding domain (A) or full Spike (B) were measured by Luminex. Background corrected data is shown and negative values were set to 100 for graphing purposes. A Kruskal-Wallis test with a Benjamini-Hochberg post-test correcting for multiple comparisons was used to test for statistical differences between wildtype variant and omicron titer. P-values for significant different features are shown above and fold change reduction of omicron titer compared to wildtype below each dataset.

Figure 2:. Vaccine induced Fcγ-receptor binding antibody profiles across SARS-CoV-2 variants of concern.

Individuals either received the full dose regimen of the BNT162b2(n = 11), mRNA-1273(n=14), or the aluminum adjuvanted inactivated particle vaccine CoronaVac (n=13). Samples were profiled at peak immunogenicity 2 weeks after the last dose. Binding to FcγR2a, FcγR2b, FcγR3a and FcγR3b of D614G (WT), Alpha (B1.117), Beta (B1.351), Delta (B.1.617.2), and Omicron (B1.529) variant of concern receptor binding domain (A) or full Spike (B) specific antibodies were determined by Luminex. Background corrected data is shown and negative values were set to 100 for graphing purposes. A Kruskal-Wallis test with a Benjamini-Hochberg post-test correcting for multiple comparisons was used to test for statistical differences between wildtype variant and omicron titer. P-values for significant different features are shown above and fold change reduction of omicron titer compared to wildtype below each dataset.