CN103330935A - 果糖作为疫苗佐剂的应用 - Google Patents
果糖作为疫苗佐剂的应用 Download PDFInfo
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- 229930091371 Fructose Natural products 0.000 title claims abstract description 24
- 239000005715 Fructose Substances 0.000 title claims abstract description 24
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 title claims abstract description 24
- 239000012646 vaccine adjuvant Substances 0.000 title claims abstract description 16
- 229940124931 vaccine adjuvant Drugs 0.000 title claims abstract description 16
- 229960005486 vaccine Drugs 0.000 claims abstract description 38
- 229960001212 bacterial vaccine Drugs 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 10
- 230000002238 attenuated effect Effects 0.000 claims description 6
- 230000002068 genetic effect Effects 0.000 claims description 6
- 229940031551 inactivated vaccine Drugs 0.000 claims description 6
- LKDRXBCSQODPBY-ZXXMMSQZSA-N alpha-D-fructopyranose Chemical compound OC[C@]1(O)OC[C@@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-ZXXMMSQZSA-N 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 2
- 230000036039 immunity Effects 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 abstract 1
- 235000004279 alanine Nutrition 0.000 abstract 1
- 238000010171 animal model Methods 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 239000002671 adjuvant Substances 0.000 description 8
- 241000894006 Bacteria Species 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 4
- 241000607471 Edwardsiella tarda Species 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000646933 Edwardsiella tarda EIB202 Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 239000000568 immunological adjuvant Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- AEMOLEFTQBMNLQ-UHFFFAOYSA-N 3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound OC1OC(C(O)=O)C(O)C(O)C1O AEMOLEFTQBMNLQ-UHFFFAOYSA-N 0.000 description 1
- FRXSZNDVFUDTIR-UHFFFAOYSA-N 6-methoxy-1,2,3,4-tetrahydroquinoline Chemical compound N1CCCC2=CC(OC)=CC=C21 FRXSZNDVFUDTIR-UHFFFAOYSA-N 0.000 description 1
- 238000009631 Broth culture Methods 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 230000000240 adjuvant effect Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BJHIKXHVCXFQLS-UYFOZJQFSA-N fructose group Chemical group OCC(=O)[C@@H](O)[C@H](O)[C@H](O)CO BJHIKXHVCXFQLS-UYFOZJQFSA-N 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
本发明涉及生物医药领域,具体公开了果糖作为疫苗佐剂的应用。本发明通过在疫苗添加或不添加果糖,发现试验动物在添加果糖后较不添加丙氨酸的死亡率显著减少,说明果糖可提高疫苗的免疫效果,可以作为疫苗的免疫佐剂。
Description
技术领域
本发明涉及生物医药领域,更具体地,涉及果糖作为疫苗佐剂的应用。
背景技术
果糖是一种最为常见的己酮糖。存在于蜂蜜、水果中,和葡萄糖结合构成日常食用的蔗糖。果糖中含6个碳原子,也是一种单糖,是葡萄糖的同分异构体,它以游离状态大量存在于水果的浆汁和蜂蜜中,果糖还能与葡萄糖结合生成蔗糖。纯净的果糖为无色晶体,熔点为103~105℃,它不易结晶,通常为黏稠性液体,易溶于水、乙醇和乙醚。果糖是最甜的单糖。在医药工业中主要用于药用辅料、解酒制品。
疫苗佐剂是一类同抗原一起或预先注射进机体,能增强机体对该抗原的免疫应答或改变免疫应答类型的物质。目前最经典的疫苗佐剂是弗氏佐剂,但该佐剂主要用于动物实验,但动物多次注射后常会发生佐剂病。因此发现新的安全、有效、不会引起毒副作用的免疫佐剂具有很重要的应用价值。
发明内容
本发明所要解决的技术问题是,为了克服现有技术中疫苗佐剂种类的不足,提供果糖作为疫苗佐剂的应用。
本发明所要解决的上述技术问题通过以下技术方案予以解决:
果糖或其衍生物或其盐在制备疫苗佐剂方面的应用。
作为一种优选方案,所述的疫苗为灭活疫苗、减毒活疫苗或基因重组疫苗。
作为一种进一步优选方案,所述的疫苗为活菌疫苗。
作为一种最优选方案,所述的疫苗为,活迟钝爱德华菌疫苗。
果糖在制备疫苗佐剂中的应用。
作为一种优选方案,所述的疫苗为灭活疫苗、减毒活疫苗或基因重组疫苗。
作为一种进一步优选方案,所述的疫苗为活菌疫苗。
作为一种最优选方案,所述的疫苗为,活迟钝爱德华菌疫苗。
果糖作为疫苗佐剂在制备疫苗中的应用。
作为一种优选方案,所述的疫苗为灭活疫苗、减毒活疫苗或基因重组疫苗。
作为一种进一步优选方案,所述的疫苗为活菌疫苗。
作为一种最优选方案,所述的疫苗为,活迟钝爱德华菌疫苗。
作为一种优选的方案,所述的疫苗为注射制剂,果糖在所述注射制剂中的含量为1μmoL~1mol。
佐剂是非特异性免疫增强剂,当与抗原一起注射或预先注入机体时,可增强机体对抗原的免疫应答或改变免疫应答类型。可以作为佐剂的物质,例如弗氏佐剂,对所有疫苗均具有佐剂作用。故果糖作为佐剂同样可用于任何种类疫苗佐剂。
本发明具有如下有益效果:(1)本发明提供了一种新型的疫苗免疫佐剂;(2)本发明所述的免疫佐剂安全、有效、不会引起毒副作用。
具体实施方式
以下结合具体实施例来进一步解释本发明,但实施例对本发明不做任何形式的限定。
实施例1迟钝爱德华菌EIB202菌株的培养和处理
挑取胰蛋白胨大豆肉汤培养基(TSB)平板上的迟钝爱德华菌EIB202单克隆于TSB试管中,30℃培养24h,按照1:100转接于100mL的TSB培养基中扩大培养。当OD600值达到1.0时离心收菌,用生理盐水洗涤两次后,用生理盐水悬浮菌体使OD600为1.0(细菌数约109个菌/毫升),用于实验小鼠的攻毒。
同时另取部分细菌用生理盐水稀释10倍(约108cfu/mL),得活菌疫苗,用于实验小鼠的活菌免疫。
实施例2小鼠的免疫试验
90只4周龄昆明鼠(平均体重25g)随机分配成3组:活菌免疫组、活菌+果糖免疫组、对照组。活菌免疫组每只小鼠腹腔注射上述制备好的活菌疫苗100μL(约107个细菌),活菌+果糖免疫组中的添加果糖组每只小鼠腹腔注射同样的活菌疫苗100μL和内含10μmol果糖的混合液。对照组每只小鼠腹腔注射100μL的生理盐水。连续免疫两次,间隔7天。最后1次免疫后7天,观察15天,统计小鼠的死亡情况。根据公式(相对免疫保护率=[1-(免疫对象的死亡率/未免疫对象的死亡率)]×100%)计算相对免疫保护率。结果见表1。
表1小鼠的免疫效果
RPS为相对保护率,1是与与生理盐水对照组相比;2是与活菌疫苗免疫组相比;*P<0.05,**P<0.01。
此结果表明,活菌疫苗免疫动物后,与生理盐水对照组相比,免疫效果有显著性提高。而活菌疫苗同时添加果糖后,比单纯使用活菌疫苗的保护率又提高了53.3%。此结果说明,果糖能够提高活菌疫苗的保护效率。
Claims (10)
1.果糖或其衍生物或其盐在制备疫苗佐剂方面的应用。
2.根据权利要求1所述的应用,其特征在于,所述的疫苗为灭活疫苗、减毒活疫苗或基因重组疫苗。
3.根据权利要求1所述的应用,其特征在于,所述的疫苗为活菌疫苗。
4.果糖在制备疫苗佐剂中的应用。
5.根据权利要求4所述的应用,其特征在于,所述的疫苗为灭活疫苗、减毒活疫苗或基因重组疫苗。
6.根据权利要求4所述的应用,其特征在于,所述的疫苗为活菌疫苗。
7.果糖作为疫苗佐剂在制备疫苗中的应用。
8.根据权利要求7所述的应用,其特征在于,所述的疫苗为灭活疫苗、减毒活疫苗或基因重组疫苗。
9.根据权利要求7所述的应用,其特征在于,所述的疫苗为活菌疫苗。
10.根据权利要求7所述的应用,其特征在于所述的疫苗为注射制剂,果糖在所述注射制剂中的含量为1μmoL~1mol。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001064225A1 (en) * | 2000-03-01 | 2001-09-07 | Societe Des Produits Nestle S.A. | Carbohydrate formulation (prebiotic adjuvant) for enhancement of immune response |
WO2001093029A2 (en) * | 2000-05-31 | 2001-12-06 | Sun Microsystems, Inc. | Speculative program execution with value prediction |
WO2008039390A2 (en) * | 2006-09-22 | 2008-04-03 | Government Of The Usa., Dept. Of Health & Human Services | Compositions and methods for chitosan enhanced immune response |
WO2009080719A1 (en) * | 2007-12-21 | 2009-07-02 | Glaxosmithkline Biologicals S.A. | Vaccine |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001064225A1 (en) * | 2000-03-01 | 2001-09-07 | Societe Des Produits Nestle S.A. | Carbohydrate formulation (prebiotic adjuvant) for enhancement of immune response |
WO2001093029A2 (en) * | 2000-05-31 | 2001-12-06 | Sun Microsystems, Inc. | Speculative program execution with value prediction |
WO2008039390A2 (en) * | 2006-09-22 | 2008-04-03 | Government Of The Usa., Dept. Of Health & Human Services | Compositions and methods for chitosan enhanced immune response |
WO2009080719A1 (en) * | 2007-12-21 | 2009-07-02 | Glaxosmithkline Biologicals S.A. | Vaccine |
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