Mapping of Pre-Existing Humoral Immunity to AAV and Natural AAV Capsid Presence in Human Tissues: Observations from a Polish Surgical Cohort.
9 affiliations
- 1Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, Szaserów 128, 01-141 Warsaw, Poland.
- 2BioMedChem Doctoral School of the University of Lodz and Lodz Institutes of the Polish Academy of Sciences, 21/23 Matejki Street, 90-237 Lodz, Poland.
- 3Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland.
- 4Department of General, Oncological, Metabolic and Thoracic Surgery, Military Institute of Medicine-National Research Institute, Szaserów 128, 01-141 Warsaw, Poland.
- 5Faculty of Medicine, University of Warsaw, Żwirki I Wigury 61, 02-091 Warsaw, Poland.
- 6Department of General, Functional and Oncological Urology, Military Institute of Medicine-National Research Institute, Szaserów 128, 01-141 Warsaw, Poland.
- 7Department of Cardiac Surgery, Military Institute of Medicine-National Research Institute, Szaserów 128, 01-141 Warsaw, Poland.
- 8Department of Gynaecology and Oncological Gynaecology, Military Institute of Medicine-National Research Institute, Szaserów 128, 01-141 Warsaw, Poland.
- 9Translational Vectorology Group, Children's Medical Research Institute, University of Sydney, Sydney, NSW 2145, Australia.
Abstract
Vectors based on adeno-associated viruses (AAVs) are widely used as a delivery system in gene therapy. However, preexisting immunity against AAV remains a major limitation. This study examines the prevalence of AAV genomes and anti-AAV2 immunity in a Polish cohort of adult patients undergoing planned surgical interventions, which serves as a random sample of the general Polish population. The presence of AAV capsid sequences was analyzed in tissue samples using PCR and endogenous AAVs were detected in 33.95% of samples. Anti-AAV2 IgG antibodies were measured by a single point ELISA and were present in 80.93% of patients. Neutralizing activity was evaluated using an AAV2 transduction inhibition assay in HEK293T cells, revealing a 60% reduction in functional activity by patients' sera. Tissue AAV PCR-positivity was associated with stronger neutralizing activity although the correlation with seropositivity was not as strong. These results suggest that pre-existing humoral immunity against AAV is common in the Polish adult population, indicating frequent exposure to naturally occurring AAVs. The findings provide important data on pre-existing anti-AAV immunity-a key factor considered in clinical trials and gene therapy development. Furthermore, the identification of naturally occurring AAV variants in human tissues points to the potential use of new sources of capsids with potentially distinct biological properties, which could contribute to the advancement of gene therapies.
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BibTeX
@article{majewska2026mapping,
title = {{Mapping of Pre-Existing Humoral Immunity to AAV and Natural AAV Capsid Presence in Human Tissues: Observations from a Polish Surgical Cohort.}},
author = {Aleksandra Majewska and Klara Weronika Siejda and Maciej Kowalec and Karolina Aleksandrowicz and Yuliia Panchuk and Małgorzata Marta Rogala and Karolina Pianka and Aleksandra Minich and Weronika Jarocka and Maciej Walędziak and Katarzyna Komorowska and Andrzej Kwiatkowski and Sylwia Rydzik and Tomasz Syryło and Agnieszka Bajek and Michał Wiłkojć and Leszek Gryszko and Grzegorz Suwalski and Jakub Mróz and Michał Zembala and Jacek Doniec and Klaudia Klarysa Brodaczewska and Leszek Lisowski},
journal = {Viruses},
year = {2026},
month = oct,
doi = {10.3390/v18101134},
url = {https://europepmc.org/article/MED/42944054},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mapping of Pre-Existing Humoral Immunity to AAV and Natural AAV Capsid Presence in Human Tissues: Observations from a Polish Surgical Cohort.
AU - Aleksandra Majewska
AU - Klara Weronika Siejda
AU - Maciej Kowalec
AU - Karolina Aleksandrowicz
AU - Yuliia Panchuk
AU - Małgorzata Marta Rogala
AU - Karolina Pianka
AU - Aleksandra Minich
AU - Weronika Jarocka
AU - Maciej Walędziak
AU - Katarzyna Komorowska
AU - Andrzej Kwiatkowski
AU - Sylwia Rydzik
AU - Tomasz Syryło
AU - Agnieszka Bajek
AU - Michał Wiłkojć
AU - Leszek Gryszko
AU - Grzegorz Suwalski
AU - Jakub Mróz
AU - Michał Zembala
AU - Jacek Doniec
AU - Klaudia Klarysa Brodaczewska
AU - Leszek Lisowski
PY - 2026
DA - 2026/10/13
JO - Viruses
DO - 10.3390/v18101134
UR - https://europepmc.org/article/MED/42944054
AB - Vectors based on adeno-associated viruses (AAVs) are widely used as a delivery system in gene therapy. However, preexisting immunity against AAV remains a major limitation. This study examines the prevalence of AAV genomes and anti-AAV2 immunity in a Polish cohort of adult patients undergoing planned surgical interventions, which serves as a random sample of the general Polish population. The presence of AAV capsid sequences was analyzed in tissue samples using PCR and endogenous AAVs were detected in 33.95% of samples. Anti-AAV2 IgG antibodies were measured by a single point ELISA and were present in 80.93% of patients. Neutralizing activity was evaluated using an AAV2 transduction inhibition assay in HEK293T cells, revealing a 60% reduction in functional activity by patients' sera. Tissue AAV PCR-positivity was associated with stronger neutralizing activity although the correlation with seropositivity was not as strong. These results suggest that pre-existing humoral immunity against AAV is common in the Polish adult population, indicating frequent exposure to naturally occurring AAVs. The findings provide important data on pre-existing anti-AAV immunity-a key factor considered in clinical trials and gene therapy development. Furthermore, the identification of naturally occurring AAV variants in human tissues points to the potential use of new sources of capsids with potentially distinct biological properties, which could contribute to the advancement of gene therapies.
SN - 1999-4915
ER -