Neutralizing antibodies against AAV2, AAV5 and AAV8 in healthy and HIV-1-infected subjects in China: implications for gene therapy using AAV vectors.
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.
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.
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Q
Liu
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.
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W
Huang
Chongqing International Travel Health Care Center, Chongqing, China.
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H
Zhang
Department of In Vitro Diagnostic Reagents, National Institutes for Food and Drug Control, Beijing, China.
Y
Y
Wang
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.
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J
Zhao
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.
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A
Song
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.
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H
Xie
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.
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C
Zhao
Beijing Blood Center, Beijing, China.
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D
Gao
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.
Y
Y
Wang
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D002681:China; D000229:Dependovirus / Q000276:immunology*; D015316:Genetic Therapy; D005822:Genetic Vectors; D057809:HEK293 Cells; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D015528:HIV Seroprevalence; D006801:Humans; D008807:Mice, Inbred BALB C
D057134:Antibodies, Neutralizing