Department of Biomedical Sciences, University of Illinois, College of Medicine at Rockford, IL 61107, USA.
Vaccine. 2013 Mar 15;31(12):1616-22. doi: 10.1016/j.vaccine.2012.09.055. Epub 2012 Oct 2.
Lymphatic filariasis affects approximately 3% of the whole world population. Mass drug administration is currently the major control strategy to eradicate this infection from endemic regions by year 2020. Combination drug treatments are highly efficient in controlling the infection. However, there are no effective vaccines available for human or animal lymphatic filariasis despite the identification of several subunit vaccines. Lymphatic filariasis parasites are multicellular organisms and potentially use multiple mechanisms to survive in the host. Therefore, there is a need to combine two or more vaccine candidate antigens to achieve the desired effect. In this study we combined three well characterized vaccine antigens of Brugia malayi, heat shock protein 12.6 (HSP12.6), Abundant Larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL) as a multivalent fusion vaccine. Putative immune individuals carry circulating antibodies against all three antigens. Depletion of these antigen specific antibodies from the sera samples removed the ability of the sera to participate in the killing of B. malayi L3 in an antibody dependent cellular cytotoxicity (ADCC) mechanism. Vaccination trials in mice with a bivalent [HSP12.6+ALT-2 (HA), HSP12.6+TSP-LEL (HT) or TSP-LEL+ALT-2 (TA)] or trivalent [HSP12.6+ALT-2+TSP-LEL (HAT)] vaccines using DNA, protein or heterologous prime boost regimen showed that trivalent HAT vaccine either as protein alone or as heterologous prime boost vaccine could confer significant protection (95%) against B. malayi L3 challenge. Immune correlates of protection suggest a Th1/Th2 bias. These finding suggests that the trivalent HAT fusion protein is a promising prophylactic vaccine against lymphatic filariasis infection in human.
淋巴丝虫病影响全球约 3%的人口。大规模药物治疗是目前在 2020 年前消除该感染的主要控制策略。联合药物治疗对控制感染非常有效。然而，尽管已经鉴定出几种亚单位疫苗，但仍没有针对人类或动物淋巴丝虫病的有效疫苗。淋巴丝虫病寄生虫是多细胞生物，它们可能利用多种机制在宿主体内生存。因此，需要结合两种或更多疫苗候选抗原来达到预期的效果。在这项研究中，我们将三种经过充分表征的班氏丝虫疫苗抗原（热休克蛋白 12.6（HSP12.6）、大量幼虫转录本-2（ALT-2）和四跨膜蛋白大细胞外环（TSP-LEL））组合成一种多价融合疫苗。假定免疫个体携带针对所有三种抗原的循环抗体。从血清样本中耗尽这些抗原特异性抗体，会消除血清参与抗体依赖细胞毒性（ADCC）机制杀伤班氏丝虫 L3 的能力。用双价疫苗（HSP12.6+ALT-2（HA）、HSP12.6+TSP-LEL（HT）或 TSP-LEL+ALT-2（TA））或三价疫苗（HSP12.6+ALT-2+TSP-LEL（HAT））在小鼠中进行的疫苗接种试验表明，三价 HAT 疫苗无论是单独作为蛋白疫苗还是作为异源初免-加强疫苗，都可以对班氏丝虫 L3 攻击提供显著保护（95%）。保护的免疫相关性提示 Th1/Th2 偏向。这些发现表明，三价 HAT 融合蛋白是一种有前途的预防淋巴丝虫病感染的人类疫苗。
