Division of Infectious Diseases, Department of Medicine, Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of Ameica.
PLoS One. 2012;7(1):e29231. doi: 10.1371/journal.pone.0029231. Epub 2012 Jan 5.
DNA vaccines are a promising approach to vaccination since they circumvent the problem of vector-induced immunity. DNA plasmid cytokine adjuvants have been shown to augment immune responses in small animals and in macaques.
METHODOLOGY/PRINCIPAL FINDINGS: We performed two first in human HIV vaccine trials in the US, Brazil and Thailand of an RNA-optimized truncated HIV-1 gag gene (p37) DNA derived from strain HXB2 administered either alone or in combination with dose-escalation of IL-12 or IL-15 plasmid cytokine adjuvants. Vaccinations with both the HIV immunogen and cytokine adjuvant were generally well-tolerated and no significant vaccine-related adverse events were identified. A small number of subjects developed asymptomatic low titer antibodies to IL-12 or IL-15. Cellular immunogenicity following 3 and 4 vaccinations was poor, with response rates to gag of 4.9%/8.7% among vaccinees receiving gag DNA alone, 0%/11.5% among those receiving gag DNA+IL-15, and no responders among those receiving DNA+high dose (1500 ug) IL-12 DNA. However, after three doses, 44.4% (4/9) of vaccinees receiving gag DNA and intermediate dose (500 ug) of IL-12 DNA demonstrated a detectable cellular immune response.
CONCLUSIONS/SIGNIFICANCE: This combination of HIV gag DNA with plasmid cytokine adjuvants was well tolerated. There were minimal responses to HIV gag DNA alone, and no apparent augmentation with either IL-12 or IL-15 plasmid cytokine adjuvants. Despite the promise of DNA vaccines, newer formulations or methods of delivery will be required to increase their immunogenicity.
Clinicaltrials.gov NCT00115960 NCT00111605.
DNA 疫苗是一种有前途的疫苗接种方法，因为它们规避了载体诱导免疫的问题。DNA 质粒细胞因子佐剂已被证明可增强小动物和猕猴的免疫反应。
方法/主要发现：我们在美国、巴西和泰国进行了两项 HIV 疫苗的首次人体临床试验，使用了源自 HXB2 株的 RNA 优化截短 HIV-1 gag 基因 (p37) DNA，单独或与 IL-12 或 IL-15 质粒细胞因子佐剂的剂量递增联合使用。HIV 免疫原和细胞因子佐剂的接种通常耐受性良好，未发现与疫苗相关的重大不良事件。少数受试者出现无症状低滴度抗 IL-12 或 IL-15 抗体。3 次和 4 次接种后的细胞免疫原性较差，单独接受 gag DNA 接种的疫苗接种者中 gag 的反应率为 4.9%/8.7%，接受 gag DNA+IL-15 的疫苗接种者为 0%/11.5%，接受 DNA+高剂量（1500ug）IL-12 DNA 的疫苗接种者无应答者。然而，在接受三剂疫苗后，接受 gag DNA 和中等剂量（500ug）IL-12 DNA 的疫苗接种者中有 44.4%（4/9）表现出可检测的细胞免疫反应。
结论/意义：这种 HIV gag DNA 与质粒细胞因子佐剂的组合具有良好的耐受性。单独使用 HIV gag DNA 反应最小，并且与 IL-12 或 IL-15 质粒细胞因子佐剂没有明显增强。尽管 DNA 疫苗具有前景，但需要新的配方或传递方法来提高其免疫原性。
Clinicaltrials.gov NCT00115960 NCT00111605。
