Fusion of IgG antibodies to albumin inhibits transport across the placenta.
Document Type
Article
Publication Date
8-14-2026
Original Citation
Nilsen J,
Sand K,
Al-Khabbaz H,
van Ligtenberg L,
Mester S,
Mathiesen L,
Noordzij H,
Jensen K,
Leitzinger N,
Ottersen O,
Benjakul S,
Herigstad M,
Ruso-Julve F,
Anthi A,
Moen A,
Nyquist-Andersen M,
Gjølberg T,
Bertelsen E,
Cameron J,
Foss S,
Christianson GJ,
Schlothauer T,
Stuge T,
Knudsen L,
Sandlie I,
Roopenian DC,
Ahlen M,
Andersen J.
Fusion of IgG antibodies to albumin inhibits transport across the placenta. Sci Immunol. 2026 Aug 14;11(122):eaee5151.
Keywords
JMG, Animals, Female, Pregnancy, Humans, Placenta, Receptors, Fc, Mice, Immunoglobulin G, Histocompatibility Antigens Class I, Maternal-Fetal Exchange, Albumins, Recombinant Fusion Proteins, Mice, Inbred C57BL, Thrombocytopenia, Neonatal Alloimmune
JAX Source
Sci Immunol. 2026 Aug 14;11(122):eaee5151.
ISSN
2470-9468
PMID
42600043
DOI
https://doi.org/10.1126/sciimmunol.aee5151
Grant
Saudi m inistry of e ducation - King Abdullah Scholarship grant i D1-48834 (h .J.A.- K.), and the Alliance for l upus Research and Nih grant DK56597 (D.c .R.).
Abstract
Immunoglobulin G (IgG)-based monoclonal antibodies are effective therapies for cancer, autoimmune diseases, and migraine. However, they are actively transported across the placenta by the neonatal Fc receptor (FcRn), limiting their use during pregnancy. Using mouse models and an ex vivo human placental perfusion system, we show that although FcRn binds albumin independently of IgG, albumin is not transported to the fetus in mice or across human placental tissue. Fusion of IgG to albumin markedly reduced transplacental transport in both models while preserving the prolonged plasma half-life conferred by FcRn. Similarly, fragment antigen-binding fragments fused to engineered albumin with enhanced FcRn binding showed minimal fetal exposure. In a mouse model of fetal and neonatal alloimmune thrombocytopenia, albumin fusion of an anti-human platelet antigen IgG reduced fetal antibody transfer and attenuated thrombocytopenia in the offspring. These findings identify albumin as an attractive fusion partner for biologics intended to minimize fetal exposure during pregnancy.