Prospects of developing a prophylactic vaccine against human lymphatic filariasis - evaluation of protection in non-human primates.
Prospects of developing a prophylactic vaccine against human lymphatic filariasis - evaluation of protection in non-human primates.
复制标题
DOI：
10.1016/j.ijpara.2018.04.002
复制
发表时间：
2018-08
影响因子：
4
通讯作者：
Kalyanasundaram R
中科院分区：
文献类型：
--
作者：
Khatri V;Chauhan N;Vishnoi K;von Gegerfelt A;Gittens C;Kalyanasundaram R
淋巴丝虫病（LF）影响着全世界1.2亿人，另有8.56亿人面临感染风险。由世界卫生组织牵头的大规模药物管理局（MDA）是目前控制这种感染的唯一战略。最近的报告表明，尽管进行了几轮MDA，但尚未实现消除，因此需要更严格的控制策略来控制LF。一种有效的预防性疫苗与MDA的组合具有显着的潜力。初步试验使用预防性三价重组马来丝虫热休克蛋白12.6，丰富的幼虫转录本2和四跨膜蛋白大细胞外环（rBmHAT）疫苗在我们的实验室开发的猕猴只提供35%的保护。因此，本研究的重点是改进目前的疫苗配方，以获得更好的保护，在非人灵长类动物。我们对当前配方进行了两项修改：（i）添加另一种抗原，过氧化硫氧还蛋白（TPX-2），使其成为四价疫苗（rBmHAXT）;（ii）加入佐剂; AL 019（明矾加葡萄糖基脂质佐剂稳定的乳液）已知可以促进平衡的Th 1/Th 2反应。对40只猕猴进行双盲接种试验，将其分为3个治疗组和1个对照组（n= 10只/组）。接种的动物以月间隔接受4次免疫接种，使用150 μg/ml的rBmHAT加明矾、rBmHAT加AL 019或rBmHAXT加AL 019。对照动物仅接受AL 019。与对照组相比，所有接种疫苗的猕猴均产生显著（P≤0.003）滴度的抗原特异性IgG抗体（1：20，000）。末次给药后1个月，对所有猕猴进行s.c.攻毒。130-180 B。马来语L3 s。我们的结果显示，与AL 019对照相比，给予改进的rBmHAXT疫苗的10只猕猴中有7只（70%）没有发生感染，其中10只猕猴中有7只发生感染。免疫动物的抗原特异性IgG 1和IgG 2抗体滴度显著升高（P≤0.01），分泌IL-4和IFN-γ的抗原应答记忆T细胞百分比增加。这些研究表明，改进的制剂（rBmHAXT加AL 019）是一种有前途的候选疫苗，对人类淋巴丝虫病。
Lymphatic filariasis (LF) affects 120 million people around the world and another 856 million people are at risk of acquiring the infection. Mass Drug Administration (MDA) spearheaded by the World Health Organization is the only current strategy to control this infection. Recent reports suggest that despite several rounds of MDA, elimination has not been achieved and there is a need for more stringent control strategies for control of LF. An effective prophylactic vaccine combined with MDA has significant potential. Initial trials using a prophylactic trivalent recombinant Brugia malayi heat shock protein 12.6, abundant larval transcript 2 and tetraspanin large extra cellular loop (rBmHAT) vaccine developed in our laboratory conferred only 35% protection in macaques. Therefore, the focus of the present study was to improve the current vaccine formulation to obtain better protection in non-human primates. We made two modifications to the current formulation: (i) the addition of another antigen, thioredoxin peroxide (TPX-2) to make it a tetravalent vaccine (rBmHAXT) and (ii) the inclusion of an adjuvant; AL019 (alum plus glucopyranosyl lipid adjuvant-stable emulsion) that is known to promote a balanced Th1/Th2 response. A double-blinded vaccination trial was performed with 40 macaques that were divided into three treatment groups and one control group (n= 10/group). Vaccinated animals received 4 immunizations at month intervals with 150 μg/ml of rBmHAT plus alum, rBmHAT plus AL019 or rBmHAXT plus AL019. Control animals received AL019 only. All vaccinated macaques developed significant (P≤0.003) titers of antigen-specific IgG antibodies (1:20,000) compared with the controls. One month after the last dose, all macaques were challenged s.c. with 130–180 B. malayi L3s. Our results showed that seven out of 10 (70%) of macaques given the improved rBmHAXT vaccine did not develop the infection compared with AL019 controls, of which seven out of 10 macaques developed the infection. Titers of antigen-specific IgG1 and IgG2 antibodies were significantly (P≤0.01) higher in vaccinated animals and there was an increase in the percentage of IL-4 and IFN-γ secreting antigen-responding memory T cells. These studies demonstrated that the improved formulation (rBmHAXT plus AL019) is a promising vaccine candidate against human lymphatic filariasis.
登录
查看更多内容
DOI：
10.1016/0047-0740(80)90028-5
发表时间：
1980-01-01
期刊：
INTERNATIONAL JOURNAL OF NUCLEAR MEDICINE & BIOLOGY
影响因子：
--
作者：
DENHAM, DA
通讯作者：
DENHAM, DA
影响因子：
1.6
作者：
Anand, S. B.;Kodumudi, K. N.;Kaliraj, P.
通讯作者：
Kaliraj, P.
影响因子：
3.7
作者：
Dakshinamoorthy, Gajalakshmi;von Gegerfelt, Agneta;Kalyanasundaram, Ramaswamy
通讯作者：
Kalyanasundaram, Ramaswamy
DOI：
10.1007/978-90-481-9078-2_14
发表时间：
2010-01-01
期刊：
ENDOTOXINS: STRUCTURE, FUNCTION AND RECOGNITION
影响因子：
--
作者：
Fox, Christopher B.;Friede, Martin;Ireton, Gregory C.
通讯作者：
Ireton, Gregory C.
影响因子：
3.7
作者：
Dakshinamoorthy G;Samykutty AK;Munirathinam G;Shinde GB;Nutman T;Reddy MV;Kalyanasundaram R
通讯作者：
Kalyanasundaram R