Abstract
The SARS-COV-2 virus is a deadly agent of inflammatory respiratory disease.
Since 2020, studies have focused on developing new therapies based on galactose-rich IgA
antibodies. Clinical surveys have also revealed that galactose-deficient IgA1 polymerizes in
serum, producing IgA nephropathy, which is a common cause of kidney failure in young adults.
Here we show that IgA1−IgA2 dimers are efficiently and economically purified in solution via
conjugated nonionic surfactant micellar aggregates. Quantitative capture at pH 7 and extraction
at pH 6.5 can avoid antibody exposure to acidic, potentially denaturing conditions. Brij-O20
aggregates lead to the highest process yields (88−91%) and purity (94%). Recovered IgA
dimers preserve their native secondary structure and do not self-associate. Increasing the
reaction volume has little impact on yield or purity. By introducing an efficient, inexpensive IgA
purification protocol, we assist pharmaceutical firms and research laboratories in developing
new IgA-based therapies as well as in increasing our understanding of IgA1 polymerization.
Since 2020, studies have focused on developing new therapies based on galactose-rich IgA
antibodies. Clinical surveys have also revealed that galactose-deficient IgA1 polymerizes in
serum, producing IgA nephropathy, which is a common cause of kidney failure in young adults.
Here we show that IgA1−IgA2 dimers are efficiently and economically purified in solution via
conjugated nonionic surfactant micellar aggregates. Quantitative capture at pH 7 and extraction
at pH 6.5 can avoid antibody exposure to acidic, potentially denaturing conditions. Brij-O20
aggregates lead to the highest process yields (88−91%) and purity (94%). Recovered IgA
dimers preserve their native secondary structure and do not self-associate. Increasing the
reaction volume has little impact on yield or purity. By introducing an efficient, inexpensive IgA
purification protocol, we assist pharmaceutical firms and research laboratories in developing
new IgA-based therapies as well as in increasing our understanding of IgA1 polymerization.
| Original language | English |
|---|---|
| Article number | https://doi.org/10.1021/acsmedchemlett.4c00128 |
| Pages (from-to) | 979-986 |
| Number of pages | 8 |
| Journal | ACS Medicinal Chemistry Letters |
| Volume | 15 |
| Issue number | 6 |
| State | Published - 15 May 2024 |
Keywords
- Antibody
- IgA
- Ligand-free
- Nonchromatographic
- Purification
- Surfactant