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Neutralizing antibodies against AAV2, AAV5 and AAV8 in healthy and HIV-1-infected subjects in China: implications for gene therapy using AAV vectors

Gene Therapy volume 21, pages 732–738 (2014)Cite this article

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Abstract

Adeno-associated viruses (AAV) have attracted attention as potential vectors for gene therapy and vaccines against several diseases, including HIV-1 infection. However, the presence of neutralizing antibodies (NAbs) after natural AAV infections inhibits their transfection in re-exposed subjects. To identify candidate AAV vectors for therapeutic or prophylactic HIV vaccines, NAbs against AAV2, AAV5 and AAV8 were screened in the sera of healthy individuals in China and 10 developed countries and an HIV-1-infected Chinese population. Seroprevalence was higher for AAV2 (96.6%) and AAV8 (82.0%) than for AAV5 (40.2%) in normal Chinese subjects. Among individuals seropositive for AAV5, >80% had low NAb titers (<1:90). The prevalence and titers of NAbs against the three AAVs were significantly higher in China than in developed countries (P<0.01). The prevalence of NAbs against AAV5 did not differ significantly between healthy and HIV-1-infected Chinese subjects (P=0.39). Co-occurrence of NAbs against AAV2, AAV5, and AAV8 was observed in the healthy population, and 15, 41, and 41% of individuals were AAV2+, AAV2+/AAV8+, and AAV2+/AAV5+/AAV8+, respectively. Therefore, AAV5 exposure is low in healthy and HIV-1-infected populations Chinese individuals, and vectors based on AAV5 may be appropriate for human gene therapy or vaccines.

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Acknowledgements

We thank Dr Xiaoyan Dong for providing the rAAV–Fluc and AAV vectors. We also thank Dr Xuerong Jia of the Beijing Wantai Biological Pharmacy, Dr Furong Ren of the Beijing Red Cross Blood Center, Professor Jingyun Li of the Beijing Institute of Microbiology and Epidemiology and Dr Lisi Yao of the Chinese Academy of Inspection and Quarantine for providing the human sera. The cooperation of the human donors involved in the epidemiological study is greatly appreciated. This study was supported by grants from the National Science and Technology Major Project (2012ZX10004701-001). The funder had no role in the study design, data collection or analysis, decision to publish or the preparation of the manuscript.

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Authors and Affiliations

  1. Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, China

    Q Liu, W Huang, J Zhao, A Song, H Xie, C Zhao & Y Wang

  2. Chongqing International Travel Health Care Center, Chongqing, China

    H Zhang

  3. Department of In Vitro Diagnostic Reagents, National Institutes for Food and Drug Control, Beijing, China

    Y Wang

  4. Beijing Blood Center, Beijing, China

    D Gao

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  1. Q Liu
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Correspondence to Y Wang.

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Liu, Q., Huang, W., Zhang, H. et al. Neutralizing antibodies against AAV2, AAV5 and AAV8 in healthy and HIV-1-infected subjects in China: implications for gene therapy using AAV vectors. Gene Ther 21, 732–738 (2014). https://doi.org/10.1038/gt.2014.47

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