Expression of HIV-1 broadly neutralizing antibodies mediated by recombinant adeno-associated virus 8 in vitro and in vivo.
Despite unremitting efforts since the discovery of human immunodeficiency virus type 1 (HIV-1), an effective vaccine has not been generated. Viral vector-mediated transfer for expression of HIV-1 broadly neutralizing antibodies (BnAbs) is an attractive strategy. In this study, a recombinant adeno-associated virus 8 (rAAV8) vector was used to encode full-length antibodies against HIV-1 in 293T cells and Balb/c mice after gene transfer. The 10E8 or NIH45-46 BnAb was expressed from a single open reading frame by linking the heavy and light chains with a furin cleavage and a 2A self-processing peptide (F2A). The results showed that the BnAbs could be expressed in the 293T cell culture medium. A single intramuscular injection of rAAV8 led to long-term expression of BnAbs in Balb/c mice. The expressed antibodies in the supernatant of 293T cells and in Balb/c mice showed neutralization effects against HIV-1 pseudoviruses. Combined immunization of rAAV8 expressing 10E8 and rAAV8 expressing NIH45-46 in Balb/c mice could increase these neutralization effects on strains of HIV-1 sensitive to 10E8 or NIH45-46 antibody compared with a single injection of rAAV8 expressing either antibody alone. Therefore, the combined immunization may be a potential vaccine approach against HIV-1.
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, 130012, Jilin, China.
Yongjiao
Y
Yu
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, 130012, Jilin, China.
Lu
L
Fu
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, 130012, Jilin, China.
Xiaoyu
X
Jiang
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, 130012, Jilin, China.
Shanshan
S
Guan
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, 130012, Jilin, China.
Ziyu
Z
Kuai
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, 130012, Jilin, China; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, 130012, Jilin, China.
Wei
W
Kong
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, 130012, Jilin, China. Electronic address: yhshi@jlu.edu.cn.
Yuhua
Y
Shi
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, 130012, Jilin, China; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, 130012, Jilin, China. Electronic address: shanym@jlu.edu.cn.
Yaming
Y
Shan
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D015153:Blotting, Western; D000229:Dependovirus; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies
Adeno-associated virus; Broadly neutralizing antibody; Gene transfer; HIV-1