Diverse IgG subclass responses to adeno‐associated virus infection and vector administration
Open accessAbstract
Humoral immune responses occur following exposure to Adeno‐associated virus (AAV) or AAV vectors. Many studies characterized antibody responses to AAV, but human IgG subclass responses to AAV have not been previously described. In this study, IgG subclass responses were examined in serum samples of normal human subjects exposed to wild‐type AAV, subjects injected intramuscularly with AAV vectors and subjects injected intravascularly with AAV vectors. A diversity of IgG subclass responses to AAV capsid were found in different subjects. IgG1 was found to be the dominant response. IgG2, IgG3, and IgG4 responses were also observed in most normal human subjects; IgG2 and IgG3 each represented the major fraction of total anti‐AAV capsid IgG in a subset of normal donors. Subjects exposed to AAV vectors showed IgG responses to AAV capsid of all four IgG subclasses. IgG responses to AAV capsid in clinical trial subjects were inversely proportional to the level of pre‐existing anti‐AAV antibody and independent of the vector dose. The high levels of anti‐AAV capsid IgG1 can mask differences in IgG2, IgG3, and IgG4 responses that were observed in this study. Analysis of IgG subclass distribution of anti‐AAV capsid antibodies indicates a complex, non‐uniform pattern of responses to this viral antigen. J. Med. Virol. 81:65–74, 2009. © 2008 Wiley‐Liss, Inc.
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Characterization of anti-AAV neutralizing antibodies showed IgG1 is the dominant subclass among neutralizing antibodies, followed by IgG2 and IgM.
“Characterization of anti-AAV NAbs showed IgG1 is the dominant subclass among Nabs, followed by IgG2 and IgM [74].”
From Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer (2023) · cites this paper as [74]
The donor-to-donor variability is likely due to heterogeneity in antibody subclasses and function or different complement levels that vary by individual or age.
“likely due to heterogeneity in the antibody subclasses and function (50, 51) or different complement levels that vary in each individual or with age, (37).”
From Pre-existing humoral immunity and complement pathway contribute to immunogenicity of adeno-associated virus (AAV) vector in human blood (2022) · cites this paper as [50]
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- Authors
- Murphy, S. L., Li, H., Mingozzi, F., Sabatino, D. E., Hui, D. J., Edmonson, S. A., & High, K. A.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Corresponding author
- High, Katherine A.
- Venue
- Journal of Medical Virology
- Publisher
- Wiley
- Published
- 2008-11-21
- Volume
- 81
- Issue
- 1
- Pages
- 65-74
- ISSN
- 0146-6615 (ISSN-L)
- 1096-9071
- PMC
- PMC2782623
- OpenAlex
- W1577558588
- Cited by
- 101
- References
- 36
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 7 · 2021: 5 · 2020: 12 · 2019: 5 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 4 · 2013: 6 · 2012: 8
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Medical Virology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (P01HL064190, P01HL078810)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- adeno-associated virus, IgG subclasses, humoral immune response, adeno-associated virus vectors, intramuscular injection, intravascular injection
- MeSH terms
- Dependovirus, Adolescent, Adult, Aged, Antibodies, Viral, Capsid, Genetic Vectors, Humans, Immunoglobulin G, Immunoglobulin M, Middle Aged, Neutralization Tests, Parvoviridae Infections
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