Effective induction of protective systemic immunity with nasally administered vaccines adjuvanted with IL-1.
Effective induction of protective systemic immunity with nasally administered vaccines adjuvanted with IL-1.
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DOI：
10.1016/j.vaccine.2010.08.006
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发表时间：
2010-10-04
期刊：
影响因子：
5.5
通讯作者：
Staats, Herman F.
中科院分区：
文献类型：
--
作者：
Gwinn, William M.;Kirwan, Shaun M.;Wang, Sheena H.;Ashcraft, Kathleen A.;Sparks, Neil L.;Doil, Catherine R.;Tlusty, Tom G.;Casey, Leslie S.;Hollingshead, Susan K.;Briles, David E.;Dondero, Richard S.;Hickey, Anthony J.;Foster, W. Michael;Staats, Herman F.
IL-1α和IL-1β在小鼠和兔鼻腔注射蛋白抗原后，观察了它们对诱导血清抗体应答的佐剂活性。小鼠鼻腔注射(I.N.)肺炎球菌表面蛋白A或破伤风类毒素与IL-1β联合免疫可产生与肠外免疫相当的保护性免疫。用IL-1佐剂疫苗鼻腔免疫清醒(即未麻醉)兔可诱导高度多变的血清抗体反应，但在诱导抗原特异性血清抗体方面不如肠外免疫有效。然而，I.N.用rPA+IL-1α免疫深度麻醉兔，虽然鼻腔免疫诱导的致死毒素中和效价低于肌注免疫诱导的致死毒素中和效价，但诱导的rPA特异性血清Ig G-EL ISA滴度与rPA+明矾肌肉注射(IM)免疫后无显著差异。放射性核素扫描显示麻醉兔鼻腔免疫的免疫原性增强与鼻内皮细胞滞留增加有关。提供不透气的放射性标记胶体颗粒。我们的结果表明，在小鼠中，IL-1是鼻用疫苗诱导保护性系统免疫的有效佐剂，而在非啮齿动物物种中，用鼻用疫苗有效地诱导系统免疫可能需要确保疫苗充分保留在鼻腔内的配方。
IL-1α and IL-1β were evaluated for their ability to provide adjuvant activity for the induction of serum antibody responses when nasally-administered with protein antigens in mice and rabbits. In mice, intranasal (i.n.) immunization with pneumococcal surface protein A (PspA) or tetanus toxoid (TT) combined with IL-1β induced protective immunity that was equivalent to that induced by parenteral immunization. Nasal immunization of awake (i.e., not anesthetized) rabbits with IL-1-adjuvanted vaccines induced highly variable serum antibody responses and was not as effective as parenteral immunization for the induction of antigen-specific serum IgG. However, i.n. immunization of deeply anesthetized rabbits with rPA + IL-1α consistently induced rPA-specific serum IgG ELISA titers that were not significantly different than those induced by intramuscular (IM) immunization with rPA + alum although lethal toxin neutralizing titers induced by nasal immunization were lower than those induced by IM immunization. Gamma scintigraphy demonstrated that the enhanced immunogenicity of nasal immunization in anesthetized rabbits correlated with an increased nasal retention of i.n. delivered non-permeable radio-labeled colloidal particles. Our results demonstrate that, in mice, IL-1 is an effective adjuvant for nasally-administered vaccines for the induction of protective systemic immunity and that in non-rodent species, effective induction of systemic immunity with nasally-administered vaccines may require formulations that ensure adequate retention of the vaccine within the nasal cavity.
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影响因子：
5.5
作者：
Beyer, WEP;Palache, AM;Osterhaus, ADME
通讯作者：
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影响因子：
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作者：
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