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Prevalence of Neutralizing Antibodies against Adeno-Associated Virus Serotypes 1, 2, and 9 in Non-Injected Latin American Patients with Heart Failure—ANVIAS Study

Neutralizing antibody (NAb) activity against the viral capsid of adeno-associated viral (AAV) vectors decreases transduction efficiency, thus limiting transgene expression. Several reports have mentioned a variation in NAb prevalence according to age, AAV serotype, and, most importantly, geographic...

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Autores principales: Sierra-Delgado, Julieth A., Likhite, Shibi, Bautista, Paula K., Gómez-Ochoa, Sergio A., Echeverría, Luis E., Guío, Elizabeth, Vargas, Clara, Serrano, Norma C., Meyer, Kathrin C., Rincon, Melvin Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051173/
https://www.ncbi.nlm.nih.gov/pubmed/36982654
http://dx.doi.org/10.3390/ijms24065579
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author Sierra-Delgado, Julieth A.
Likhite, Shibi
Bautista, Paula K.
Gómez-Ochoa, Sergio A.
Echeverría, Luis E.
Guío, Elizabeth
Vargas, Clara
Serrano, Norma C.
Meyer, Kathrin C.
Rincon, Melvin Y.
author_facet Sierra-Delgado, Julieth A.
Likhite, Shibi
Bautista, Paula K.
Gómez-Ochoa, Sergio A.
Echeverría, Luis E.
Guío, Elizabeth
Vargas, Clara
Serrano, Norma C.
Meyer, Kathrin C.
Rincon, Melvin Y.
author_sort Sierra-Delgado, Julieth A.
collection PubMed
description Neutralizing antibody (NAb) activity against the viral capsid of adeno-associated viral (AAV) vectors decreases transduction efficiency, thus limiting transgene expression. Several reports have mentioned a variation in NAb prevalence according to age, AAV serotype, and, most importantly, geographic location. There are currently no reports specifically describing the anti-AAV NAb prevalence in Latin America. Here, we describe the prevalence of NAb against different serotypes of AAV vectors (AAV1, AAV2, and AAV9) in Colombian patients with heart failure (HF) (referred to as cases) and healthy individuals (referred to as controls). The levels of NAb were evaluated in serum samples of 60 subjects from each group using an in vitro inhibitory assay. The neutralizing titer was reported as the first dilution inhibiting ≥50% of the transgene signal, and the samples with neutralizing titers at ≥1:50 dilution were considered positive. The prevalence of NAb in the case and control groups were similar (AAV2: 43% and 45%, respectively; AAV1 33.3% in each group; AAV9: 20% and 23.2%, respectively). The presence of NAb for two or more of the serotypes analyzed was observed in 25% of the studied samples, with the largest amount in the positive samples for AAV1 (55–75%) and AAV9 (93%), suggesting serial exposures, cross-reactivity, or coinfection. Moreover, patients in the HF group exhibited more common combined seropositivity for NAb against AAV1 d AAV9 than those in the control group (91.6% vs. 35.7%, respectively; p = 0.003). Finally, exposure to toxins was significantly associated with the presence of NAb in all regression models. These results constitute the first report of the prevalence of NAb against AAV in Latin America, being the first step to implementing therapeutic strategies based on AAV vectors in this population in our region.
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spelling pubmed-100511732023-03-30 Prevalence of Neutralizing Antibodies against Adeno-Associated Virus Serotypes 1, 2, and 9 in Non-Injected Latin American Patients with Heart Failure—ANVIAS Study Sierra-Delgado, Julieth A. Likhite, Shibi Bautista, Paula K. Gómez-Ochoa, Sergio A. Echeverría, Luis E. Guío, Elizabeth Vargas, Clara Serrano, Norma C. Meyer, Kathrin C. Rincon, Melvin Y. Int J Mol Sci Article Neutralizing antibody (NAb) activity against the viral capsid of adeno-associated viral (AAV) vectors decreases transduction efficiency, thus limiting transgene expression. Several reports have mentioned a variation in NAb prevalence according to age, AAV serotype, and, most importantly, geographic location. There are currently no reports specifically describing the anti-AAV NAb prevalence in Latin America. Here, we describe the prevalence of NAb against different serotypes of AAV vectors (AAV1, AAV2, and AAV9) in Colombian patients with heart failure (HF) (referred to as cases) and healthy individuals (referred to as controls). The levels of NAb were evaluated in serum samples of 60 subjects from each group using an in vitro inhibitory assay. The neutralizing titer was reported as the first dilution inhibiting ≥50% of the transgene signal, and the samples with neutralizing titers at ≥1:50 dilution were considered positive. The prevalence of NAb in the case and control groups were similar (AAV2: 43% and 45%, respectively; AAV1 33.3% in each group; AAV9: 20% and 23.2%, respectively). The presence of NAb for two or more of the serotypes analyzed was observed in 25% of the studied samples, with the largest amount in the positive samples for AAV1 (55–75%) and AAV9 (93%), suggesting serial exposures, cross-reactivity, or coinfection. Moreover, patients in the HF group exhibited more common combined seropositivity for NAb against AAV1 d AAV9 than those in the control group (91.6% vs. 35.7%, respectively; p = 0.003). Finally, exposure to toxins was significantly associated with the presence of NAb in all regression models. These results constitute the first report of the prevalence of NAb against AAV in Latin America, being the first step to implementing therapeutic strategies based on AAV vectors in this population in our region. MDPI 2023-03-14 /pmc/articles/PMC10051173/ /pubmed/36982654 http://dx.doi.org/10.3390/ijms24065579 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sierra-Delgado, Julieth A.
Likhite, Shibi
Bautista, Paula K.
Gómez-Ochoa, Sergio A.
Echeverría, Luis E.
Guío, Elizabeth
Vargas, Clara
Serrano, Norma C.
Meyer, Kathrin C.
Rincon, Melvin Y.
Prevalence of Neutralizing Antibodies against Adeno-Associated Virus Serotypes 1, 2, and 9 in Non-Injected Latin American Patients with Heart Failure—ANVIAS Study
title Prevalence of Neutralizing Antibodies against Adeno-Associated Virus Serotypes 1, 2, and 9 in Non-Injected Latin American Patients with Heart Failure—ANVIAS Study
title_full Prevalence of Neutralizing Antibodies against Adeno-Associated Virus Serotypes 1, 2, and 9 in Non-Injected Latin American Patients with Heart Failure—ANVIAS Study
title_fullStr Prevalence of Neutralizing Antibodies against Adeno-Associated Virus Serotypes 1, 2, and 9 in Non-Injected Latin American Patients with Heart Failure—ANVIAS Study
title_full_unstemmed Prevalence of Neutralizing Antibodies against Adeno-Associated Virus Serotypes 1, 2, and 9 in Non-Injected Latin American Patients with Heart Failure—ANVIAS Study
title_short Prevalence of Neutralizing Antibodies against Adeno-Associated Virus Serotypes 1, 2, and 9 in Non-Injected Latin American Patients with Heart Failure—ANVIAS Study
title_sort prevalence of neutralizing antibodies against adeno-associated virus serotypes 1, 2, and 9 in non-injected latin american patients with heart failure—anvias study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051173/
https://www.ncbi.nlm.nih.gov/pubmed/36982654
http://dx.doi.org/10.3390/ijms24065579
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