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The level of protection against rotavirus shedding in mice following immunization with a chimeric VP6 protein is dependent on the route and the coadministered adjuvant

机译:嵌合VP6蛋白质免疫后小鼠对轮状病毒脱落的保护水平取决于途径和共同使用的佐剂

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Intranasal (i.n.) immunization of BALB/c mice with chimeric murine rotavirus EDIM (epizootic diarrhea of infant mice) VP6 and attenuated E. coli heat-labile toxin (LT), LT(R192G), stimulated >99% protection against rotavirus shedding after EDIM challenge. Here, we evaluated other potential adjuvants with chimeric VP6 administered by two mucosal routes: i.n. and oral. Besides LT(R192G), the adjuvants examined included Adjumer(R), CpG oligodeoxynucleotides (CpG ODN), chimeric Al subunit of cholera toxin (CTA1)-DD, and QS-21. All except QS-21 significantly (P < 0.05) increased VP6-specific serum I-G responses after i.n. immunization, but none significantly increased these responses when administered orally. The i.n. delivery of chimeric VP6 alone induced both rotavirus IgG1 and IgG2a whose relative titers suggested a skewed Th2-like response. Inclusion of Adjumer(R) greatly increased Th2-like responses, while CpG ODN shifted the response to a less Th2-like response. The adjuvants CTAI-DD, LT(R192G), QS-21 had no significant effect on ratios of IgG1/IgG2a titers. Following EDIM challenge of mice immunized i.n. with chimeric VP6 and either LT(R192G), CTA1-DD, Adjumer(R) or CpG ODN, shedding was reduced >99, 95, 80, 74, respectively, relative to that found in unimmunized mice (P < 0.05). QS-21 induced less protection (43%, not significant (N.S.)) while immunization with chimeric VP6 alone reduced shedding by only 16% (N.S.). Oral immunization with chimeric VP6 and all selected adjuvants except QS-21 was less effective than after i.n. immunization, with protection levels of 94 (P < 0.05), 71 (P < 0.05), 55, 35 and 28% for LT(R192G), QS-21, CpG ODN, CTA1-DD, and Adjumer(R), respectively, while immunization with chimeric VP6 alone gave no protection. Thus, different adjuvants induced different degrees of protection and oral immunization was generally less effective then the i.n. route,
机译:嵌合鼠轮状病毒EDIM(婴儿小鼠的流行性腹泻)VP6的鼻内(中)免疫和减毒的大肠杆菌不耐热毒素(LT),LT(R192G),在轮状病毒脱落后刺激了> 99%的保护EDIM挑战。在这里,我们评估了通过两种粘膜途径施用嵌合VP6的其他潜在佐剂。和口头的。除LT(R192G)外,检查的佐剂还包括Adjumer(R),CpG寡脱氧核苷酸(CpG ODN),霍乱毒素的嵌合Al亚基(CTA1)-DD和QS-21。除QS-21外,所有其他药物均显着(P <0.05)在i.n后增加VP6-特异性血清I-G反应。口服免疫,但没有一个能显着增加这些反应。 i.n.嵌合VP6的单独递送会诱导轮状病毒IgG1和IgG2a,它们的相对滴度表明有类似Th2的应答。包含Adjumer(R)大大增加了Th2样反应,而CpG ODN将反应转变为更少的Th2样反应。佐剂CTAI-DD,LT(R192G),QS-21对IgG1 / IgG2a效价比没有明显影响。 EDIM攻击后,对小鼠进行免疫接种。与嵌合VP6和LT(R192G),CTA1-DD,Adjumer(R)或CpG ODN相比,与未免疫小鼠相比,脱落分别减少了> 99、95、80、74(P <0.05)。 QS-21诱导的保护作用较小(43%,不显着(N.S.)),而仅用嵌合VP6进行的免疫减少的脱落仅16%(N.S。)。用嵌合的VP6和除QS-21以外的所有选择的佐剂进行的口服免疫效果不如免疫后。免疫,LT(R192G),QS-21,CpG ODN,CTA1-DD和Adjumer(R)的保护水平分别为94(P <0.05),71(P <0.05),55、35和28% ,而仅使用嵌合VP6进行免疫接种没有提供任何保护。因此,不同的佐剂诱导不同程度的保护,口服免疫通常不如免疫接种有效。路线,

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