Paul Rajkumar, Ilamaran Meganathan, Khatri Vishal, Amdare Nitin, Reddy Maryada Venkata Rami, Kaliraj Perumal
Centre for Biotechnology, Anna University, Sardar Patel Road, Guindy, Chennai 600025, Tamil Nadu, India.
Department of Biochemistry & J.B. Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India.
Parasite Epidemiol Control. 2019 Feb 7;4:e00092. doi: 10.1016/j.parepi.2019.e00092. eCollection 2019 Feb.
Filariasis, a neglected tropical helminth disease needs vaccine besides mass drug administration for its successful eradication.
An attempt was made to produce a fusion protein (P-TUFT-ALT-2) of abundant larval transcript protein-2 and Tuftsin to enhance its immunogenicity. The fusion construct was expressed in , a nonexpensive commercial expression system. This study focused on the evaluation of immunological response produced by P-TUFT-ALT-2 in Balb/c mice.
P-TUFT-ALT-2 showed an enhanced IgG peak titre compared to expressed E-ALT-2 and expressed P-ALT-2. IgG2b, IgG2a and IgG1 production were predominant indicating a balanced Th1/Th2 response. P-TUFT-ALT-2 also induced about 28% and 9.5% higher splenocyte proliferation over control and E-ALT-2 respectively. Splenocytes produced predominant IFN-γ followed by IL-5, IL-2 and IL-10 specifying a balanced Th1/Th2 response. P-TUFT-ALT-2 showed 55% to 80% with an average of 65% cytotoxicity in L3 larvae in ADCC assay.
This experiment validates P-TUFT-ALT-2 as a potential vaccine candidate for human lymphatic filariasis.
丝虫病是一种被忽视的热带蠕虫病,除大规模药物给药外,还需要疫苗才能成功根除。
尝试生产丰富幼虫转录蛋白-2和吞噬细胞增强蛋白的融合蛋白(P-TUFT-ALT-2)以增强其免疫原性。融合构建体在一种廉价的商业表达系统中表达。本研究重点评估P-TUFT-ALT-2在Balb/c小鼠中产生的免疫反应。
与表达的E-ALT-2和表达的P-ALT-2相比,P-TUFT-ALT-2显示出更高的IgG峰值滴度。IgG2b、IgG2a和IgG1的产生占主导地位,表明Th1/Th2反应平衡。与对照和E-ALT-2相比,P-TUFT-ALT-2还分别诱导脾细胞增殖提高约28%和9.5%。脾细胞产生的主要是IFN-γ,其次是IL-5、IL-2和IL-10,表明Th1/Th2反应平衡。在ADCC试验中,P-TUFT-ALT-2对L3幼虫的细胞毒性显示为55%至80%,平均为65%。
本实验验证了P-TUFT-ALT-2作为人类淋巴丝虫病潜在疫苗候选物的有效性。