Cross-protection against challenge with Puumala virus after immunization with nucleocapsid proteins from different hantaviruses
Cross-protection against challenge with Puumala virus after immunization with nucleocapsid proteins from different hantaviruses
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DOI：
10.1128/jvi.76.13.6669-6677.2002
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发表时间：
2002-07-01
影响因子：
5.4
通讯作者：
Lundkvist, Å
中科院分区：
文献类型：
--
作者：
Nicacio, CD;Della Valle, MG;Lundkvist, Å
汉坦病毒是啮齿动物传播的病原体，可引起人类肾综合征出血热或汉坦病毒肺综合征。核衣壳蛋白（N）在汉坦病毒中相对保守，并且在实验室动物和人类中都具有高度免疫原性，并且已显示其在动物模型中诱导有效的保护性免疫。为了研究来自不同汉坦病毒的重组N（rN）引起交叉保护的能力，我们用来自Puumala（PUUV）、Topografov（TOPV）、安第斯山脉（ANDV）和Dobrava（DOBV）病毒的rN免疫银行田鼠，随后用PUUV攻击它们。用PUUV和TOPV rN免疫的所有动物均得到完全保护。在DOBV rN免疫组中，10只动物中有7只受到保护，而在ANDV rN免疫组中，8只动物中只有3只受到保护，这与PUUV rN比DOBV rN更密切相关。还研究了rN免疫后的体液和细胞免疫应答。在ANDV rN免疫动物的血清中检测到对PUUV抗原的最高交叉反应性体液应答，其次是TOPV rN免疫动物的血清，并且在DOBV rN免疫动物的血清中仅观察到非常低的抗体交叉反应性。在增殖试验中，来自用所有异源rN免疫的动物的T淋巴细胞在体外被PUUV rN有效地召回，来自用同源蛋白免疫的动物的T淋巴细胞也是如此。总之，这项研究表明，汉坦病毒N可以引起对PUUV的交叉保护性免疫应答，结果表明，在rN引起的交叉保护中，免疫应答的细胞臂比不道德臂发挥更重要的作用。
Hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome in humans. The nucleocapsid protein (N) is relatively conserved among hantaviruses and highly immunogenic in both laboratory animals and humans, and it has been shown to induce efficient protective immunity in animal models. To investigate the ability of recombinant N (rN) from different hantaviruses to elicit cross-protection, we immunized bank voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized with PUUV and TOPV rN were completely protected. In the group immunized with DOBV rN, 7 of 10 animals were protected, while only 3 of 8 animals were protected in the group immunized with ANDV rN, which is more closely related to PUUV rN than DOBV rN. Humoral and cellular immune responses after rN immunization were also investigated. The highest cross-reactive humoral responses against PUUV antigen were detected in sera from ANDV rN-immunized animals, followed by those from TOPV rN-immunized animals, and only very low antibody cross-reactivity was observed in sera from DOBV rN-immunized animals. In proliferation assays, T lymphocytes from animals immunized with all heterologous rNs were as efficiently recalled in vitro by PUUV rN as were T lymphocytes from animals immunized with homologous protein. In summary, this study has shown that hantavirus N can elicit cross-protective immune responses against PUUV, and the results suggest a more important role for the cellular arm of the immune response than for the Immoral arm in cross-protection elicited by rN.