Prevalence Of Neutralizing Antibodies Against Aav8, Aav9, And Aav843 In A Chinese Population

Adeno-associated virus (MV) is a tiny, non-enveloped, and single stranded DNA virus that requires helper viruses to promote efficient replication. Recombinant AAV has been extensively studied as the most potential vector for gene therapy. However, the presence of AAV neutralizing antibodies is one of the key factors impairing the efficiency of transduction. Two natural serotypes, AAV8 and AAV9, have lower neutralizing antibody titers. They have been considered as candidate serotypes for gene therapy in European and Japanese populations. However, the prevalence of neutralizing antibodies of the above two AAV serotypes in the Chinese population remains unclear. Recently, neutralizing antibodies (NAbs) against two natural AAVs (AAV8 and AAV9) and one novel serotype (AAV843) that were derived from DNA shuffling were investigated in the serum of 154 Chinese people. Results showed that the prevalence of AAV8, AAV9, and AAV843 NAbs was 38.3%, 35.7% and 25.5%, respectively. In addition, although the prevalence of NAbs in these three AAV serotypes was increased with age, in AAV9 and AAV843 it was more robustly increased with age (<= 10, 11-20, 21-30, & 31-40 vs >= 41, P<0.001). Ninety-one people (59%) had none of these three serotypes, but 37 people (24%) were positive for all three AAV serotypes. In the 154 people, only 6 samples were positive for single AAV8 NAb, while 4 samples were positive for single AAV9 Nabs. However, single AAV843 NAbs was not detected in any. Comparing titers in people with two or more NAbs, AAV8 Nab titer was higher than that of AAV9 in 90.7% of the samples (P<0.05). AAV843 Nab titer was always the lowest. In summary, prevalence of AAV8 and AAV9 was low in the Chinese population. AAV843 NAb was almost non-existent. AAV8, AAV9, and AAV843 can be used as candidate serotypes for gene therapy in Chinese populations, but AAV843 is the most optimal. The current study provides an important logical basis for development of gene therapy drugs using these serotypes.