Details

Autor(en) / Beteiligte

• Gardner, Matthew R.
• Mendes, Desiree E.
• Muniz, Claudia P.
• Martinez-Navio, José M.
• Fuchs, Sebastian P.
• Gao, Guangping
• Desrosiers, Ronald C.

Titel

High concordance of ELISA and neutralization assays allows for the detection of antibodies to individual AAV serotypes

Ist Teil von

• Molecular therapy. Methods & clinical development, 2022-03, Vol.24, p.199-206

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Prescreening of participants in clinical trials that use adeno-associated virus (AAV) vectors is required to identify naive participants, as preexisting neutralizing antibodies can limit the efficacy of AAV gene therapies. The presence of antibodies to individual AAV serotypes is typically detected by neutralization assay. To streamline the screening process, we compared an ELISA-based screening method with a neutralization assay for the detection of antibodies against AAV1, AAV8, and AAV9 in a collection of 50 rhesus macaque sera and 20 human sera. We observed a high level of concordance between the two assays (Pearson r > 0.8) for all three serotypes in both sample sets. We thus investigated pre- vs post-vector inoculation sera samples from rhesus macaques that received AAV1 or AAV8 vector inoculations for cross-reactive anti-AAV antibodies. All 12 macaques seroconverted to the vector they received, but many also reacted to the other serotypes. Our results validate an easy-to-use ELISA for reliable detection of antibodies to individual serotypes of AAV. Our results also demonstrate that an antibody response post-AAV inoculation may partially cross-react with other AAV serotypes. Overall, these results suggest that either assay can be used by academic labs for prescreening samples for preexisting anti-AAV antibodies. [Display omitted] As more studies deploy novel AAV gene therapies, the need has grown for identifying hosts negative for anti-AAV capsid antibodies. Gardner et al. compare and show a high degree of correlation between an ELISA and neutralization assay to identify hosts negative for binding and neutralizing antibodies against AAV capsids.