Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Effect of aggregate seeding on protein stability in solution

Västberg, Amanda LU ; Markova, Natalia ; Nilsson, Lars LU ; King, Patrick ; Schaefer, Jan ; Sivakumar, Balasubramanian ; Sjögren, Helen ; Wahlgren, Marie LU orcid and Elofsson, Ulla (2026) In Journal of Drug Delivery Science and Technology 120.
Abstract

The stability of therapeutic proteins is crucial for maintaining their efficacy and safety. Misfolded or aggregated proteins can accelerate aggregation by a seeding effect, altering protein stability and interactions. Heat-induced aggregates can pose a risk because they can have perturbed structures that expose aggregate-prone regions. This study explored seeding by heat-induced protein aggregates on the stability and aggregation of two therapeutic proteins, human growth hormone (hGH) and a monoclonal Antibody (Antibody A), during storage of two weeks at three relevant temperatures of 4 °C, room temperature (RT, 21-23 °C), and 40 °C. Grwoth of aggregates were seen in the sub-micron-sized aggregates by Dynamic Light Scattering at 4 °C or... (More)

The stability of therapeutic proteins is crucial for maintaining their efficacy and safety. Misfolded or aggregated proteins can accelerate aggregation by a seeding effect, altering protein stability and interactions. Heat-induced aggregates can pose a risk because they can have perturbed structures that expose aggregate-prone regions. This study explored seeding by heat-induced protein aggregates on the stability and aggregation of two therapeutic proteins, human growth hormone (hGH) and a monoclonal Antibody (Antibody A), during storage of two weeks at three relevant temperatures of 4 °C, room temperature (RT, 21-23 °C), and 40 °C. Grwoth of aggregates were seen in the sub-micron-sized aggregates by Dynamic Light Scattering at 4 °C or RT. Furthermore, heated Antibody A showed signs of reversibility of higher-order structure after storage. Samples stored at 4 °C and RT showed similar stability and aggregation behaviour. While two weeks of storage at 40 °C accelerated the structural degradation of both proteins, it did not accelerate aggregation or particle formation for either hGH or Antibody A.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Heat-induced aggregation, Human growth hormone, Monoclonal antibody, Seeding
in
Journal of Drug Delivery Science and Technology
volume
120
article number
108193
publisher
Editions de Sante
external identifiers
  • scopus:105031928994
ISSN
1773-2247
DOI
10.1016/j.jddst.2026.108193
language
English
LU publication?
yes
id
eec5cff9-3b2a-4e31-9bff-e619297d0725
date added to LUP
2026-04-29 10:29:59
date last changed
2026-04-30 03:04:32
@article{eec5cff9-3b2a-4e31-9bff-e619297d0725,
  abstract     = {{<p>The stability of therapeutic proteins is crucial for maintaining their efficacy and safety. Misfolded or aggregated proteins can accelerate aggregation by a seeding effect, altering protein stability and interactions. Heat-induced aggregates can pose a risk because they can have perturbed structures that expose aggregate-prone regions. This study explored seeding by heat-induced protein aggregates on the stability and aggregation of two therapeutic proteins, human growth hormone (hGH) and a monoclonal Antibody (Antibody A), during storage of two weeks at three relevant temperatures of 4 °C, room temperature (RT, 21-23 °C), and 40 °C. Grwoth of aggregates were seen in the sub-micron-sized aggregates by Dynamic Light Scattering at 4 °C or RT. Furthermore, heated Antibody A showed signs of reversibility of higher-order structure after storage. Samples stored at 4 °C and RT showed similar stability and aggregation behaviour. While two weeks of storage at 40 °C accelerated the structural degradation of both proteins, it did not accelerate aggregation or particle formation for either hGH or Antibody A.</p>}},
  author       = {{Västberg, Amanda and Markova, Natalia and Nilsson, Lars and King, Patrick and Schaefer, Jan and Sivakumar, Balasubramanian and Sjögren, Helen and Wahlgren, Marie and Elofsson, Ulla}},
  issn         = {{1773-2247}},
  keywords     = {{Heat-induced aggregation; Human growth hormone; Monoclonal antibody; Seeding}},
  language     = {{eng}},
  publisher    = {{Editions de Sante}},
  series       = {{Journal of Drug Delivery Science and Technology}},
  title        = {{Effect of aggregate seeding on protein stability in solution}},
  url          = {{http://dx.doi.org/10.1016/j.jddst.2026.108193}},
  doi          = {{10.1016/j.jddst.2026.108193}},
  volume       = {{120}},
  year         = {{2026}},
}