Hemachandra Atchriya, Puls Rebekah L, Sirivichayakul Sunee, Kerr Stephen, Thantiworasit Pattarawat, Ubolyam Sasiwimol, Cooper David A, Emery Sean, Phanuphak Praphan, Kelleher Anthony, Ruxrungtham Kiat
HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Hum Vaccin. 2010 Oct;6(10):835-40. doi: 10.4161/hv.6.10.12635. Epub 2010 Oct 1.
Previously demonstrated safe and highly immunogenic in non-human primates, this study assessed DNA (pHIS-HIV-AE) prime, recombinant fowlpox (rFPV-HIV-AE) boost vaccines in humans.
Eight participants (6 active vaccine, 2 placebo) received all vaccinations; local and systemic reactions were mild to moderate. The percentage CD4(+) and CD8(+) T cells responding to HIV-1 Gag antigens by ICS (mean ± SD) was 0.16 ± 0.12 and 0.10 ± 0.12 for active and 0.01 ± 0.01 and 0.00 ± 0.00 for placebo vaccine respectively. The percentage of T cells responding did not reach pre-defined thresholds to be considered positive responses. Consequently, the Data Safety Monitoring Board recommended cessation of further recruitment. Existing volunteers were followed to 52 weeks.
Vectors expressing homologous HIV-1 clade A/E gag, pol, env and regulatory genes or matched placebo were administered intramuscularly at weeks 0, 4, 8 (6 mg pHIS-HIV-AE) and week 12 (3.0 x 10(8) pfu rFPV-HIV-AE) in this randomized, double-blind, placebo-controlled phase I/IIa study in healthy Thai adults at low risk of HIV infection. Immunogenicity was determined by interferon-gamma and IL-2 expression using intracellular cytokine staining assay (ICS), 13 weeks after randomization. Interim analysis was performed when eight volunteers reached 16 weeks follow-up.
Vaccine candidates were generally well tolerated, but showed limited immunogenicity. Better vaccines and delivery systems are required.
此前已证明在非人灵长类动物中安全且具有高度免疫原性，本研究评估了DNA（pHIS-HIV-AE）初免、重组鸡痘病毒（rFPV-HIV-AE）加强疫苗在人体中的效果。
8名参与者（6名接种活性疫苗，2名接种安慰剂）完成了所有疫苗接种；局部和全身反应为轻度至中度。通过细胞内细胞因子染色分析（ICS）检测，接种活性疫苗者中对HIV-1 Gag抗原产生反应的CD4(+)和CD8(+) T细胞百分比（均值±标准差）分别为0.16±0.12和0.10±0.12，接种安慰剂疫苗者分别为0.01±0.01和0.00±0.00。产生反应的T细胞百分比未达到被视为阳性反应的预定义阈值。因此，数据安全监测委员会建议停止进一步招募。对现有志愿者进行了52周的随访。
在这项针对低感染HIV风险的泰国健康成年人的随机、双盲、安慰剂对照的I/IIa期研究中，于第0、4、8周（6毫克pHIS-HIV-AE）和第12周（3.0×10(8) 空斑形成单位rFPV-HIV-AE）肌肉注射表达同源HIV-1 A/E亚型gag、pol、env和调节基因的载体或匹配的安慰剂。随机分组13周后，通过细胞内细胞因子染色分析（ICS）检测干扰素-γ和IL-2表达来确定免疫原性。当8名志愿者达到16周随访时进行中期分析。
候选疫苗总体耐受性良好，但免疫原性有限。需要更好的疫苗和递送系统。
