Multigene/multisubtype HIV-1 vaccine induces potent cellular and humoral immune responses by needle-free intradermal delivery
Multigene/multisubtype HIV-1 vaccine induces potent cellular and humoral immune responses by needle-free intradermal delivery
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DOI：
10.1016/j.ymthe.2005.06.473
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发表时间：
2005-12-01
影响因子：
12.4
通讯作者：
Wahren, B
中科院分区：
文献类型：
--
作者：
Bråve, A;Ljungberg, K;Wahren, B
基因疫苗接种遇到的问题与基因治疗不同，因为基因的半衰期短和对基因产物的免疫应答强都是所希望的。我们已经评估了由编码9种HIV-1蛋白的7个质粒组成的DNA疫苗。使用无针递送装置，Biojector，连同重组小鼠GM-CSF，该疫苗在小鼠中诱导强烈的gp 160 Env-和p24 Gag-特异性细胞和体液免疫应答。rGM-CSF对于诱导针对gp 160和p24的抗体和抗原特异性CD 8（+）T细胞应答至关重要。在GLP认证的动物机构，将该疫苗的GMP生产批次（预期用于人用）皮内或肌内注射给药至BALB/c小鼠。该疫苗诱导强烈的细胞反应，与免疫途径无关;此外，在对各种组织进行组织病理学检查后，未检测到毒性体征。总之，结果表明，多基因/多亚型HIV DNA与重组GM-CSF联合皮内给药是诱导高水平特异性CD 8（+）T细胞和异常高滴度抗体的安全有效策略。该疫苗已获得瑞典药品管理局的批准，目前正在进行I期临床试验。
Gene vaccination encounters problems different from those of gene therapy since both a short half-life of the gene and a strong immune response to the gene product are desirable. We have evaluated a DNA vaccine consisting of seven plasmids encoding nine HIV-1 proteins. Using a needle-free delivery device, the Biojector, together with recombinant mouse GM-CSF, this vaccine induced strong gp160 Env- and p24 Gag-specific cellular and humoral immune responses in mice. The rGM-CSF was crucial for inducing both antibodies and antigen-specific CD8(+) T cell responses against both gp160 and p24. A GMP-produced lot of this vaccine, intended for human use, was delivered intradermally or intramuscularly into BALB/c mice at a GLP-accredited animal facility. This vaccine induced strong cellular responses independent of the route of immunization; moreover, no signs of toxicity were detected after histopathological examination of various tissues. Overall, the results indicate that the intradermal delivery of multigene/multisubtype HIV DNA in combination with recombinant GM-CSF is a safe and efficacious strategy for inducing high levels of specific CD8(+) T cells and unusually high titers of antibodies. This vaccine has been approved by the Swedish Medicinal Products Agency and is currently in a Phase I clinical trial.