Characterization of the interactions of rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG isotypes

Abstract

Despite the increasing importance of rabbit as an animal model in pharmacological studies like investigating placental transfer of therapeutic IgGs, little is known about the molecular interaction of the rabbit neonatal Fc receptor (FcRn) with rabbit and human IgG molecules. We analyzed the interactions of the rabbit and human FcRn with rabbit and human IgG isotypes using surface plasmon resonance assay. Similar to FcRn of other species, rabbit FcRn functions in pH-dependent manner, as it binds IgGs at pH 6.0, but no binding occurs at pH 7.4. We also showed that rabbit FcRn binds rabbit IgG and human IgG1 with nearly identical affinity, whereas it has stronger interactions with the other human IgG isotypes. The similar affinity of rabbit IgG and human IgG1 for rabbit FcRn was confirmed by in vitro FcRn-mediated recycling assay. These data verify that rabbit is an appropriate animal model for analyzing the pharmacokinetics of human therapeutic monoclonal antibodies.

Preventing lung pathology and mortality in rabbit Staphylococcus aureus pneumonia models with cytotoxin-neutralizing monoclonal IgGs penetrating the epithelial lining fluid

“…ASN-1 and ASN-2 serum levels peaked at approximately 0.5 mg/mL at the earliest time point measured (2 hours post dosing), and then gradually decreased resulting in a half-life of more than 5 days that is in line with reports of human IgGs in rabbits 32 . ASN-1 and ASN-2 concentrations at the different time points were very similar, and the sum of the two equaled the total human IgG level.…”

Allogenic Fc Domain-Facilitated Uptake of IgG in Nasal Lamina Propria: Friend or Foe for Intranasal CNS Delivery?

“…In contrast, Stirling et al showed in vitro that hIgG yields a higher porcine FcRn-mediated uptake [ 17 ]. These results are further supported by kinetic investigations of the rabbit FcRn that showed binding to human IgG with higher affinity than rabbit IgG in surface plasmon resonance experiments [ 56 ]. Similarly, it was reported that the serum half-life of human IgGs administered to mice is significantly lower than the half-life of murine antibodies.…”

“…Our data support the hypothesis of species-dependent IgG transport, as we did not observe significant hIgG levels in the lamina propria after 8 h of permeation. There are studies showing efficient FcRn-mediated transport of xenogenic IgGs in cell culture models that may not reflect the same conditions as under ex vivo and in vivo conditions [ 17 , 56 ]. However, we cannot exclude that other transport mechanisms than FcRn are responsible for our observations.…”

The Immature Gut Barrier and Its Importance in Establishing Immunity in Newborn Mammals

“…In the lagomorph rabbit and in precocious rodent species, i.e., the guinea pig, macromolecular transfer takes place from uterine secretion via the everted yolk sac during the fetal period (15,29). Even though the yolk sac endoderm may endocytose macromolecules indiscriminately, this transfer is selective since the yolk sac endoderm expresses FcRn that binds and mediates the transfer of IgG to the fetal circulation (18,19). Thus, guinea pigs are born relatively mature, equipped with their mother's IgG repertoire, and intestinal macromolecular transfer is negligible postnatally (20,22).…”