A combination of two Brugia malayi filarial vaccine candidate antigens (BmALT-2 and BmVAH) enhances immune responses and protection in jirds

A combination of two Brugia malayi filarial vaccine candidate antigens (BmALT-2 and BmVAH) enhances immune responses and protection in jirds
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DOI:
10.1017/s0022149x10000799
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发表时间:
2011-12-01
影响因子:
1.6
通讯作者:
Kaliraj, P.
Kaliraj, P.
中科院分区:
生物学3区
文献类型:
--
作者:
Anand, S. B.;Kodumudi, K. N.;Kaliraj, P.

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在这项研究中,评价了编码BmALT-2和BmVAH作为单一抗原或作为混合抗原的丝虫重组蛋白或DNA疫苗构建体。用DNA疫苗构建体肌肉内免疫雄性沙鼠或用蛋白质疫苗腹腔内免疫雄性沙鼠。单和双顺反子DNA构建体诱导大量的干扰素-γ反应的脾细胞;抗原特异性反应较高的双顺反子鸡尾酒构建体免疫接种后,并引起显着的保护性反应的57%,在挑战与马来丝虫,这是类似的抗体依赖性细胞毒性(ADCC)测定和免疫室实验。当用B攻击时,鸡尾酒蛋白疫苗诱导IgG 2a(Th 1)和IgG 1(Th 2)应答的混合物,具有80%的保护性应答。马来感染性幼虫然而,在用B攻击后,单蛋白疫苗rALT-2诱导的Th 2(IgG 1/IgG 3)具有70%的保护性应答,而rVAH诱导的Th 1(IgG 2a)具有较低的增殖性应答,具有60%的保护性。马来感染性幼虫这些结果表明,丝虫鸡尾酒蛋白疫苗能够引起实质性的免疫和保护性反应时,与单一抗原疫苗接种适当接种的沙鼠。
In this study filarial recombinant protein or DNA vaccine constructs encoding BmALT-2 and BmVAH as single or as cocktail antigens were evaluated. Male jirds were immunized intramuscularly with DNA vaccine constructs or were immunized intraperitoneally with protein vaccine. The single and bicistronic DNA constructs induced substantial interferon-gamma responses in spleen cells; antigen-specific responses were higher following immunization with the bicistronic cocktail construct and evoked a significant protective response of 57% in jirds challenged with Brugia malayi that was similar in the antibody-dependent cellular cytotoxicity (ADCC) assay and micropore chamber experiment. The cocktail protein vaccines induced a mixture of IgG2a (Th1) and IgG1 (Th2) responses with 80% protective response when challenged with B. malayi infective larvae. However, the single protein vaccine rALT-2 induced Th2 (IgG1/IgG3) with a 70% protective response and rVAH induced Th1 (IgG2a) with a lower proliferative response with 60% protection following challenge with B. malayi infective larvae. These results suggest that filarial cocktail protein vaccines are able to elicit substantial immune and protective responses when compared with single antigen vaccination in suitably vaccinated jirds.