Impact of FcRn antagonism on vaccine-induced protective immune responses against viral challenge in COVID-19 and influenza mouse vaccination models.

Abstract

Antagonism of the neonatal Fc receptor through an engineered antibody Fc fragment, such as efgartigimod, results in a decrease in immunoglobulin G levels. This approach is being evaluated as a therapeutic strategy for the treatment of IgG-mediated autoimmune diseases. Our goal was to evaluate the impact of mFc-ABDEG, a mouse-adapted antibody Fc fragment with a mode of action highly similar to efgartigimod, on vaccine-induced protective immune responses against viral infections. Therefore, mouse vaccination models for COVID-19 and influenza were employed, utilizing an mRNA COVID-19 vaccine (COMIRNATY) and an adjuvanted, inactivated quadrivalent influenza vaccine (Seqirus+AddaVax), respectively. In both models, vaccination induced robust humoral responses. As expected, animals treated with mFc-ABDEG had lower levels of virus-specific IgG, while virus-specific IgM responses remained unaffected. The COVID-19 vaccine induced a strong Th1-type T cell response irrespective of mFc-ABDEG treatment. Influenza vaccination resulted in a poor T cell induction, regardless of mFc-ABDEG treatment, due to the Th2-biased response that inactivated influenza vaccines typically induce. Importantly, mFc-ABDEG treatment had no effect on protective immunity against live viral challenges in both models. Vaccinated animals treated with mFc-ABDEG were equally protected as the non-treated vaccinated controls. These non-clinical data demonstrate that FcRn antagonism with mFc-ABDEG did not affect the generation of vaccine-induced protective humoral and cellular responses, or protection against viral challenges. These data substantiate the clinical observations that, although IgG titers were reduced, FcRn antagonism with efgartigimod did not impair the ability to generate new specific IgG responses, regardless of the timing of vaccination.