[Immunogenicity of recombinant adeno-asscociated virus type 1 expressing HIV-1 gp120 gene in mice and Rhesus macaques].
To study the immunogenicity of recombinant adeno-asscociated virus type 1 expressing HIV-1 gp120 gene (rAAV2/1-gp120) in BALB/c mice and Rhesus macaques. The gp120 gene derived from Chinese HIV-1 isolates was constructed into rAAV2/1 and rAd5 vectors. Firstly, the immunogenicity of rAAV2/1-gp120 was compared with rAd5-gp120 in BALB/c mice when used once or twice in 3 weeks interval. Then the monkeys were immunized with rAAV2/1-gp120 once. The HIV-1 specific IgG levels and neutralization activity to pseudotyped HIV-1 virus were tested using ELISA and neutralization assay, and the cellular immune responses were analyzed by IFN-gamma enzyme-linked immunospot (ELISPOT) and in vivo CTL assays. Compared with rAd5-gp120 immunized mice, mice immunized with rAAV2/1-gp120 once in duced stronger gp120-specific IgG and were sustained for at least 21 weeks. rAd5-gp120 immunized mice generated stronger cellular immune responses than rAAV2/1-gp120 in spleen and draining lymph node. But only moderate gp120-specific in vivo CTL activity was observed in both rAAV2/1-gp120 and rAd5-gp120 immunized mice. Four of five monkeys vaccinated with rAAV2/1-gp120 generated gp120 specific IgG, the titer ranged from 1:100 to 1:400 with end-point dilution. Gp120 specific IgG could be detected 4 weeks after immunization and reached the peak at 10 weeks after immunization. No neutralization activity against pseudotyped HIV-1 virus expressing NL4-3 Env antigen was detected. In Conclusion, rAAV2/1-gp120 induced high level of HIV-1 specific IgG antibody and moderate cellular immune responses. No neutralizing antibody was elicited. It indicates that the env gene and immunization strategy should be optimized to elicit neutralizing antibody against HIV-1 in further studies.
Yu
Shuang-Qing
SQ
State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 100052, China. yyushqing@163.com
Feng
Xia
X
Liu
Hong-Mei
HM
Yang
Hai-Ru
HR
Li
Hong-Xia
HX
Zeng
Yi
Y
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D000229:Dependovirus / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000235:genetics; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000276:immunology; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013997:Time Factors
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins