| Title: |
Stability Engineering of Recombinant Secretory IgA |
| Authors: |
Göritzer, K; Strasser, R; Ma, JK-C |
| Publisher Information: |
MDPI AG |
| Publication Year: |
2024 |
| Collection: |
St George's University of London: Repository |
| Description: |
Secretory IgA (SIgA) presents a promising avenue for mucosal immunotherapy yet faces challenges in expression, purification, and stability. IgA exists in two primary isotypes, IgA1 and IgA2, with IgA2 further subdivided into two common allotypes: IgA2m(1) and IgA2m(2). The major differences between IgA1 and IgA2 are located in the hinge region, with IgA1 featuring a 13-amino acid elongation that includes up to six O-glycosylation sites. Furthermore, the IgA2m(1) allotype lacks a covalent disulfide bond between heavy and light chains, which is present in IgA1 and IgA2m(2). While IgA1 demonstrates superior epitope binding and pathogen neutralization, IgA2 exhibits enhanced effector functions and stability against mucosal bacterial degradation. However, the noncovalent linkage in the IgA2m(1) allotype raises production and stability challenges. The introduction of distinct single mutations aims to facilitate an alternate disulfide bond formation to mitigate these challenges. We compare four different IgA2 versions with IgA1 to further develop secretory IgA antibodies against SARS-CoV-2 for topical delivery to mucosal surfaces. Our results indicate significantly improved expression levels and assembly efficacy of SIgA2 (P221R) in Nicotiana benthamiana. Moreover, engineered SIgA2 displays heightened thermal stability under physiological as well as acidic conditions and can be aerosolized using a mesh nebulizer. In summary, our study elucidates the benefits of stability-enhancing mutations in overcoming hurdles associated with SIgA expression and stability. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf; application/zip |
| Language: |
English |
| ISSN: |
1422-0067 |
| Relation: |
https://openaccess.sgul.ac.uk/id/eprint/116607/3/ijms-25-06856.pdf; https://openaccess.sgul.ac.uk/id/eprint/116607/8/ijms-25-06856-s001.zip; Göritzer, K; Strasser, R; Ma, JK-C (2024) Stability Engineering of Recombinant Secretory IgA. International Journal of Molecular Sciences, 25 (13). p. 6856. ISSN 1422-0067 https://doi.org/10.3390/ijms25136856 SGUL Authors: Ma, Julian |
| DOI: |
10.3390/ijms25136856 |
| Availability: |
https://openaccess.sgul.ac.uk/id/eprint/116607/; https://doi.org/10.3390/ijms25136856 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.62A69FAE |
| Database: |
BASE |