Homotypic protection against rotavirus-induced diarrhea in infant mice breast-fed by dams immunized with the recombinant VP8*subunit of the VP4 capsid protein

Homotypic protection against rotavirus-induced diarrhea in infant mice breast-fed by dams immunized with the recombinant VP8*subunit of the VP4 capsid protein
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DOI:
10.1089/vim.2000.13.187
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发表时间:
2000-01-01
期刊:
影响因子:
2.2
通讯作者:
Buesa, J
Buesa, J
中科院分区:
医学4区
文献类型:
--
作者:
Gil, MT;De Souza, CO;Buesa, J

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外衣壳蛋白VP 4和VP 7诱导针对轮状病毒的中和抗体。我们在小鼠模型中研究了VP 4的氨基末端胰蛋白酶片段VP 8 * 免疫介导的保护作用。用在大肠杆菌中表达的猴轮状病毒SA 11 VP 6和VP 8 * 蛋白免疫BALB/c雌性小鼠,与血清阴性雄性小鼠交配。用SA 11毒株(P5 B [2],G3)或鼠轮状病毒毒株EDIM(P10[16],G3)经口攻毒窝仔,以验证对新生儿诱导腹泻的保护程度。只有那些用VP 8 * 免疫的母鼠所生的幼仔在用SA 11菌株经口攻击后没有发生腹泻。由未经处理的母鼠所生但由VP 8 * 免疫的AMS寄养喂养的幼崽在经口感染SA 11菌株后未发生腹泻,但在用EDIM菌株攻毒时发生腹泻。这些结果支持以下概念:(1)VP 8 * 是一种高度免疫原性的多肽,其在用该抗原免疫的母鼠所生的幼崽中诱导有效的同型保护以对抗疾病,以及(2)在新生小鼠中,对抗疾病的保护是由存在于mph中的中和分泌抗体介导的,而不是由通过胎盘转移到后代的血清抗体介导的。
The outer capsid proteins VP4 and VP7 induce neutralizing antibody against rotavirus. We have investigated in a mouse model the protection mediated by immunization with VP8*, the amino-terminal tryptic fragment of VP4. BALB/c female mice immunized with simian rotavirus SA11 VP6 and VP8* proteins expressed in Escherichia coli were mated with seronegative males. Litters were orally challenged with the SA11 strain (P5B[2], G3) or with the murine rotavirus strain EDIM (P10[16], G3) to verify the degree of protection against diarrhea induced in the newborns. Only those pups born to dams immunized with VP8* did not develop diarrhea after having been orally challenged with the SA11 strain. Pups born to naive dams but foster nursed by VP8*-immunized ams did not develop diarrhea after having been orally infected with the SA11 strain, but they suffered diarrhea when challenged with the EDIM strain. These results support the concepts that (1) VP8* is a highly immunogenic polypeptide that induces effective homotypic protection against disease in pups born to dams immunized with this antigen and (2) in newborn mice the protection against disease is mediated by neutralizing secretory antibodies present in the mph rather than by serum antibodies transferred through the placenta to the offspring.