Altered IgG4 Antibody Response to Repeated mRNA versus Protein COVID Vaccines
Kalkeri, R.; Zhu, M.; Cloney-Clark, S.; Plested, J. S.; Parekh, A.; Gorinson, D.; Cai, R.; Mahato, S.; Ramanathan, P.; Aurelia, L. C.; John Selva, K.; Marchese, A. M.; Fries, L.; Chung, A. W.; Dunkle, L. M.
Show abstract
Repeated mRNA SARS-CoV-2 vaccination has been associated with increases in the proportion of IgG4 in spike-specific antibody responses and concurrent reductions in Fc{gamma}-mediated effector functions that may limit control of viral infection. Here, we assessed anti-Spike total IgG, IgG1, IgG2, IgG3 and IgG4, and surrogate markers for antibody-dependent cellular phagocytosis (ADCP, Fc{gamma}RIIa binding), antibody-dependent cellular cytotoxicity (ADCC, Fc{gamma}RIIIa binding), and antibody-dependent complement deposition (ADCD, C1q binding) associated with repeated SARS-CoV-2 vaccination with NVX-CoV2373 (Novavax Inc., Gaithersburg, MD). The NVX-CoV2373 protein vaccine did not induce notable increases in spike-specific IgG4 or negatively impact surrogates for Fc{gamma} effector responses. Conversely, repeated NVX-CoV2373 vaccination uniquely enhanced IgG3 responses which are known to exhibit strong affinity for Fc{gamma}RIIIa and have previously been linked to potent neutralization of SARS-CoV-2. Subsequent investigations will help to understand the immunological diversity generated by different SARS-CoV-2 vaccine types and have the potential to reshape public health strategies.
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