Immunoglobulins M survive low-pH conditions used for virus inactivation and for elution from bioaffinity columns

Area of Science:

• Biopharmaceutical manufacturing
• Protein stability
• Immunology

Background:

• Low pH conditions are common during biopharmaceutical manufacturing, posing a risk to protein integrity.
• Recombinant protein stability, particularly immunoglobulins M (IgMs), is critical for therapeutic applications.
• Understanding protein behavior at low pH is essential for process optimization.

Purpose of the Study:

• To assess the stability and functionality of purified immunoglobulins M (IgMs) when exposed to a low pH environment.
• To determine the impact of low pH on IgM aggregation, fragmentation, immunoreactivity, glycosylation, and thermal stability.
• To provide data supporting the use of IgMs as next-generation therapeutics.

Main Methods:

• Three distinct purified immunoglobulin M (IgM) samples were subjected to a pH of 3.5.
• The low pH exposure was maintained for a duration of 60 minutes at room temperature.
• Analytical techniques were employed to evaluate aggregation, fragmentation, immunoreactivity, glycosylation, and thermal stability post-treatment.

Main Results:

• No significant aggregation or fragmentation was observed in the treated IgM samples.
• Full immunoreactivity was retained, indicating preserved biological function.
• Intact glycosylation profiles and unchanged thermal stability confirmed the structural integrity of the IgMs.

Conclusions:

• Purified immunoglobulins M (IgMs) demonstrate remarkable stability and functional integrity when exposed to low pH conditions.
• The findings support the viability of using IgMs as next-generation therapeutics, even with potential low pH exposure during manufacturing.
• Low pH treatment did not adversely affect critical quality attributes of the tested IgMs, including immunoreactivity and glycosylation.