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首页> 外文期刊>AIDS Research and Human Retroviruses >Therapeutic vaccination using cationic liposome-adjuvanted HIV type 1 peptides representing HLA-supertype-restricted subdominant t cell epitopes: Safety, immunogenicity, and feasibility in guinea-Bissau
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Therapeutic vaccination using cationic liposome-adjuvanted HIV type 1 peptides representing HLA-supertype-restricted subdominant t cell epitopes: Safety, immunogenicity, and feasibility in guinea-Bissau

机译：使用代表HLA超型限制的主要t细胞表位的阳离子脂质体佐剂的HIV 1型肽进行的治疗性疫苗接种：在几内亚比绍的安全性，免疫原性和可行性

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摘要

We have designed a therapeutic HIV-1 vaccine concept based on peptides together with the adjuvant CAF01. Peptides represented 15 HLA-supertype- restricted subdominant and conserved CD8 T cell epitopes and three CD4 T-helper cell epitopes. In this phase I clinical trial, safety and immunogenicity were assessed in untreated HIV-1-infected individuals in Guinea-Bissau, West Africa. Twenty-three HIV-1-infected individuals were randomized to receive placebo (n=5) or vaccine (n=18). Safety was appraised by clinical follow-up combined with monitoring of biochemistry, hematology, CD4 T cell counts, and HIV-1 viral loads. T cell immunogenicity was monitored longitudinally by interferon (IFN)-γ ELISpot. New vaccine-specific T cell responses were induced in 6/14 vaccinees for whom ELISpot data were valid. CD4 T cell counts and viral loads were stable. The study shows that therapeutic immunization is feasible and safe in Guinea-Bissau and that it is possible to redirect T cell immunity with CAF01-adjuvanted HIV-1 peptide vaccine during untreated HIV-1 infection in some patients. However, relatively few preexisting and vaccine-induced HIV-1 T cell responses to CD8 T cell epitopes were detected against HIV-1 using IFN-γ ELISpot in this chronically infected African population.
机译：我们已经设计了基于肽和佐剂CAF01的治疗性HIV-1疫苗概念。肽代表15个HLA超型限制性的显性和保守CD8 T细胞表位和3个CD4 T辅助细胞表位。在这一I期临床试验中，对西非几内亚比绍未经治疗的HIV-1感染者进行了安全性和免疫原性评估。 23名感染HIV-1的患者被随机分配接受安慰剂（n = 5）或疫苗（n = 18）。通过临床随访以及对生化，血液学，CD4 T细胞计数和HIV-1病毒载量的监测相结合来评估安全性。通过干扰素（IFN）-γELISpot纵向监测T细胞的免疫原性。在ELISpot数据有效的6/14个疫苗接种者中诱导了新的疫苗特异性T细胞应答。 CD4 T细胞计数和病毒载量稳定。研究表明，在几内亚比绍进行治疗性免疫是可行且安全的，并且在某些患者未经治疗的HIV-1感染期间，可以使用CAF01辅助的HIV-1肽疫苗重新定向T细胞免疫。但是，在这个慢性感染的非洲人群中，使用IFN-γELISpot检测到的针对HIV-1的针对CD8 T细胞表位的，相对较早存在的疫苗诱导的HIV-1 T细胞应答。

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