Effects of protein aggregates: An immunologic perspective

Rosenberg, Amy S.

doi:10.1208/aapsj080359

Cited by 1,355Protein purification and stabilityBiosimilars and Bioanalytical MethodsMonoclonal and Polyclonal Antibodies Research

Effects of protein aggregates: An immunologic perspective

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Rosenberg, Amy S.·2006·The AAPS Journal

DOI 10.1208/aapsj080359PMC PMC2761057

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Abstract

The capacity of protein aggregates to enhance immune responses to the monomeric form of the protein has been known for over a half-century. Despite the clear connection between protein aggregates and antibody mediated adverse events in treatment with early therapeutic protein products such as intravenous immune globulin (IVIG) and human growth hormone, surprisingly little is known about the nature of the aggregate species responsible for such effects. This review focuses on a framework for understanding how aggregate species potentially interact with the immune system to enhance immune responses, garnered from basic immunologic research. Thus, protein antigens presented in a highly arrayed structure, such as might be found in large nondenatured aggregate species, are highly potent in inducing antibody responses even in the absence of T-cell help. Their potency may relate to the ability of multivalent protein species to extensively cross-link B-cell receptor, which (1) activates B cells via Bt kinases to proliferate, and (2) targets protein to class II major histocompatibility complex (MHC)-loading compartments, efficiently eliciting T-cell help for antibody responses. The review further focuses on protein aggregates as they affect an immunogenicity risk assessment, the use of animal models and studies in uncovering effects of protein aggregates, and changes in product manufacture and packaging that may affect generation of protein aggregates.

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Certain recombinant proteins and self-assembling peptides are immunogenic.
“Certain recombinant proteins and self-assembling peptides are immunogenic214–218.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [216]

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Authors: Rosenberg, A. S.
Affiliations: United States Food and Drug Administration (US)
Corresponding author: Rosenberg, Amy S.
Venue: The AAPS Journal
Publisher: Springer Science and Business Media LLC
Published: 2006-09
Volume: 8
Issue: 3
Pages: E501-E507
ISSN: 1550-7416 (ISSN-L)
DOI: 10.1208/aapsj080359
PMC: PMC2761057
OpenAlex: W2071095038
Cited by: 1,355
References: 44
Citations by year: 2026: 48 · 2025: 54 · 2024: 57 · 2023: 50 · 2022: 58 · 2021: 66 · 2020: 75 · 2019: 76 · 2018: 90 · 2017: 76 · 2016: 85 · 2015: 107 · 2014: 83 · 2013: 87 · 2012: 95
FWCI: 15.11
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: The AAPS Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Keywords: protein aggregates, immunogenicity, intravenous immunoglobulin, human growth hormone, therapeutic proteins, B cell receptor cross-linking, T cell help, immunogenicity risk assessment, animal models
MeSH terms: Antibodies, Antibody Formation, Proteins, Risk, Immunoglobulins, Intravenous

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