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© 2023 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

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
Author
Sierra-Delgado, Julieth A 1   VIAFID ORCID Logo  ; Likhite, Shibi 2 ; Bautista, Paula K 3   VIAFID ORCID Logo  ; Gómez-Ochoa, Sergio A 4   VIAFID ORCID Logo  ; Echeverría, Luis E 4 ; Guío, Elizabeth 3 ; Vargas, Clara 5 ; Serrano, Norma C 3 ; Meyer, Kathrin C 6   VIAFID ORCID Logo  ; Rincon, Melvin Y 3   VIAFID ORCID Logo 

 Centro de Investigaciones, Fundación Cardiovascular de Colombia, Floridablanca 681004, Colombia; Universidad Industrial de Santander, Bucaramanga 680002, Colombia 
 The Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA 
 Centro de Investigaciones, Fundación Cardiovascular de Colombia, Floridablanca 681004, Colombia 
 Clínica de Falla Cardíaca y Trasplante, Fundación Cardiovascular de Colombia, Floridablanca 681004, Colombia 
 Universidad Industrial de Santander, Bucaramanga 680002, Colombia 
 The Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA; College of Medicine, The Ohio State University, Columbus, OH 43205, USA 
First page
5579
Publication year
2023
Publication date
2023
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2791656867
Copyright
© 2023 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.