Antibody Transcytosis and Neutralizing Activity in Respiratory Epithelial Cells

Area of Science:

• Immunology
• Virology
• Respiratory Medicine

Background:

• Serum antibodies are crucial for protection against SARS-CoV-2 and influenza.
• Mechanisms of antibody transport to the respiratory tract lumen are not fully understood.
• Antibodies must reach the respiratory tract surface to neutralize viruses.

Purpose of the Study:

• Investigate the transcytosis and neutralizing activity of serum-derived IgG and IgA.
• Determine if antibodies retain activity after transport across respiratory epithelia.
• Explore the role of FcRn and pIgR in antibody transport.

Main Methods:

• Used an in vitro SARS-CoV-2 infection model with human nasal and basal epithelial cells (hNECs and hBECs).
• Confirmed expression of FcRn and pIgR receptors via qPCR, immunofluorescence, and flow cytometry.
• Assessed neutralizing activity of purified IgG and IgA against SARS-CoV-2 and influenza A virus.

Main Results:

• Both IgG and IgA were transcytosed across hNECs and hBECs, retaining neutralizing activity.
• FcRn and pIgR expression levels influenced transport efficiency, with variations between nasal and basal cells.
• IgG showed more potent neutralization than IgA, but both contributed to reducing viral infection.
• Transport efficiency differed: IgG favored hBECs, IgA favored hNECs.

Conclusions:

• Serum-derived IgG and IgA can be transported across human respiratory epithelia, maintaining antiviral activity.
• FcRn- and pIgR-mediated transport likely contributes to mucosal protection against respiratory viruses.
• Understanding these transport mechanisms can help identify protective antibody responses.