CN110302376A - 一种禽流感疫苗佐剂及应用 - Google Patents
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Abstract
本发明公开了一种禽流感疫苗佐剂及其应用，属于家禽疫病控制领域。本发明在禽流感疫苗中添加硫酸头孢喹肟佐剂，可使蛋鸡机体抗应激能力增强，死亡率下降了0.83%；采食量提前4天恢复到正常采食量，产蛋高峰期提前15天，且产蛋高峰期延长8天，产蛋量提高0.46%，使蛋鸡生产性能得到显著提升，该方法的示范推广前景广阔。
Description
技术领域
本发明属于家禽疫病控制领域，具体涉及一种禽流感疫苗佐剂及其应用。
背景技术
禽流感是禽流行性感冒的简称，分为高致性、低致病性和非致病性三大类，其中高致病性禽流感是由H5和H7亚毒株（以H5N1、H5N6和H7N9为代表）引起的。高致病性禽流感因其在禽类中传播快、危害大、病死率高，被世界动物卫生组织列为A类动物疫病，我国将其列为一类动物疫病。家禽高致病性禽流感采用疫苗接种是最好的预防办法，疫苗主要分为弱毒活疫苗、灭活油乳剂疫苗、基因工程疫苗三类。从实际效果、安全性能和经济实用性等方面综合考虑，主要以由强毒禽流感病毒制成的灭活油乳剂疫苗为主，然而此类疫苗的免疫注射家禽应激反应大，特别是对蛋鸡的产蛋率影响比较大。
研究者为降低疫苗的应激反应、免疫性差等缺陷，开发出很多类型的疫苗佐剂(Adjuvant)，疫苗佐剂是能够非特异性地改变或增强机体对抗原的特异性免疫应答、发挥辅助作用的一类物质。佐剂能够促进机体产生长期、高效的特异性免疫反应，提高机体保护能力，同时又能减少抗原的用量，降低疫苗的生产成本。疫苗佐剂种类较多，常用的有白油佐剂、氢氧化铝佐剂、蜂胶佐剂等。
硫酸头孢喹肟通过抑制细胞壁的合成达到杀菌的效果，具有广谱的抗菌活性，对青霉素酶与β-内酰胺酶稳定。体外抑菌实验表明，本品可抑制常见的革兰氏阳性和阴性细菌，包括大肠杆菌、化脓放线菌、芽孢杆菌属的细菌、棒状杆菌、金黄色葡萄球菌、链球菌、类杆菌、梭状芽孢杆菌等。通过检索发现，目前还没有将硫酸头孢喹肟作为禽流感疫苗佐剂的报道。
发明内容
针对现有技术的不足，本发明的目的在于提供一种降低禽流感疫苗应激反应、免疫性差的佐剂，本发明发现硫酸头孢喹肟可作为禽流感疫苗佐剂，达到减少机体应激反应和继发感染、提高疫苗免疫抗体水平等。
疫苗在生产和使用过程中很容易产生杂菌，在对机体进行免疫注射后，如果有杂菌随疫苗进入，增加了机体产生副反应和患病的风险，而与抗生素混合一起免疫注射可将进入家禽体内的杂菌和少部分自身体内的细菌消灭，减少机体应激反应，增强免疫效果。因此，可选择油乳剂的抗生素注射液与疫苗同用，以此仅对细菌有消灭作用，对病毒性病原不产生影响。
发明人经过大量试验和不懈努力，最终获得了一种禽流感疫苗佐剂，该禽流感佐剂为硫酸头孢喹肟佐剂。
一种禽流感疫苗佐剂的应用，将硫酸头孢喹肟佐剂与禽流感疫苗同注射，其添加比例10ml佐剂添加到每瓶500头份H5+H7的禽流感疫苗中。
优选地，如上所述的一种禽流感疫苗佐剂，所述硫酸头孢喹肟佐剂可用于鸡的流感防治。
与现有技术相比，本发明的优点为：
1、本发明首次发现，硫酸头孢喹肟可作为禽流感疫苗佐剂，二者同时注射后可使蛋鸡机体抗应激能力增强，死亡率下降了0.83%，采食量提前4天恢复到正常采食量，产蛋高峰期提前15天，且产蛋高峰期延长8天，产蛋量提高0.46% ，蛋鸡生产性能得到显著提升。
2、硫酸头孢喹肟佐剂只对细菌有消灭作用，对病毒性病原不产生影响；且硫酸头孢喹肟佐剂为中性酸碱度，对疫苗的pH值不产生影响，所以两者结合使用，不存在排异性。
3、本发明的实施将会显著提升蛋鸡养殖场经济效益，示范推广前景广阔。
具体实施例
以下是对本发明的技术方案做进一步描述，但本发明的内容不仅仅局限于实施例所述的范围，凡是不背离本发明构思的改变或等同替代均包括在本发明的保护范围之内。
实施例1
长期以来，禽流感主要以H5N1免疫为主，随着H7N9禽流感防控形势日益严峻，禽流感疫苗在2017年由原来的H5亚型三价灭活疫苗（Re-6-7-8株）变为H5+H7的双联苗。发明人开展了疫苗中添加硫酸头孢喹肟佐剂在禽流感免疫效果的作用研究试验。
、试验蛋鸡场情况
蛋鸡场位于沙洋县拾桥镇东风村八组，远离人群密集区，自然防疫条件好，地理位置优越。该场为荆门市神羽禽业有限公司合作社的一个代养场，该养殖场为新场，没有发生过重大动物疫病，饲养能力为11000只蛋鸡，符合实验室所需样品数量要求。
、试验疫苗和兽药
禽流感二价灭活疫苗（H5+H7）,吉林冠界生物技术有限公司生产，生产批号：201802012；硫酸头孢喹肟注射液由四川恒通动物制药有限公司生产，规格10ml:0.25g;包装：10ml×2瓶；生产批号：20171203。
、试验方法
3.1试验动物：本实验选择生产周期长的蛋鸡作为研究对象,首次选择1200只16日龄的蛋鸡进行免疫试验，用同批次的1200只蛋鸡做为对照组。75日龄进行第二次免疫试验，在开产前105日龄进行第三次免疫试验。
3.2免疫方法：将10ml:0.25g规格的硫酸头孢喹肟注射液做为佐剂，按10ml添加到每瓶500头份H5+H7禽流感疫苗中的比例，充分混匀后，对试验的1200只蛋鸡进行免疫注射，注射部位为颈部皮下，每只注射0.3ml。对比组的蛋鸡也同样进行免疫注射，但是疫苗中不添加硫酸头孢喹肟佐剂。第二次、第三次免疫试验方法同第一次免疫试验，只是注射剂量都变为0.5ml。（疫苗操作说明规定2周龄每只注射0.3ml，5周龄以上鸡每只0.5ml。）
免疫后，观察试验动物有无副反应，采食量变化、发病和死淘、对产蛋的影响等情况，做好相关记录。
、高致病性禽流感（H5+H7）灭活苗疫苗抗体检测情况
4.1、采血：一次性采血器前腔静脉采血，每份不少于2ml。采血后，将采血器活塞外拉预留血清析出空间，并塞上护针帽，去除推杆，在采血器上标明样品编号。在实验室中，静置2小时后离心机3500G离心6分钟，分离血清。
采血试验蛋鸡数量和对照组蛋鸡数量各定为160只。分别于37日龄（一免后21天）、96日龄（二免后21天）、126日龄（三免后21天），各采血一次，分离血清做禽流感免疫抗体检测试验。
、抗体检测方法：按照国标《高致病性禽流感诊断技术》（GB/T18936-2003）中血凝和血凝抑制试验（HA-HI）进行，具体操作步骤参照试剂盒说明书。
、抗体检测结果
本试验均在免疫注射后21天进行了抗体监测，第一次免疫实验组抗体合格率为：0.78，对照组抗体合格率为：0.73；第二次免疫实验组抗体合格率为：0.96，对照组抗体合格率为：0.95；第三次免疫实验组抗体合格率为：0.98，对照组抗体合格率为：0.96,三次免疫试验中试验组和对照组抗体平均合格率差异不显著（P>0.05）。
调查试验期间副反应发病死亡情况：本试验第一次试验组1200只蛋鸡免疫后没有应激死亡，对照组无死亡；第二次试验组1200只蛋鸡免疫后没有应激死亡，对照组死亡4只；第三次试验组1200只蛋鸡免疫后应激死亡2只，对照组死亡8只。三次试验中试验组共死亡2只，对照组死亡12只。通过对比观察，三次免疫注射后，试验组和对照组均出现了采食量下降，但是试验组3天恢复到平时采食量，而对照组7天恢复正常采食。添加硫酸头孢喹肟佐剂的试验组，达到90%的产蛋高峰比对照组提前了15天，且产蛋高峰期延长了8天，产蛋量提高了0.46%，显著提高了养鸡场的经济效益。
Claims (3)
1.一种禽流感疫苗佐剂，其特征在于：该禽流感疫苗佐剂为硫酸头孢喹肟佐剂。
2.一种禽流感疫苗佐剂的应用，其特征在于：将硫酸头孢喹肟佐剂与禽流感疫苗同注射。
3.如权利要求2所述的一种禽流感疫苗佐剂的应用，其特征在于：所述硫酸头孢喹肟佐剂可用于鸡的流感防治。
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| WO2022018576A1 (en) * | 2020-07-20 | 2022-01-27 | Phibro Animal Health Corporation | Controlled release vaccine formulation |
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| CN1882360A (zh) * | 2003-11-21 | 2006-12-20 | 辉瑞产品公司 | 抗生素作为疫苗佐剂的用途 |
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| CN1882360A (zh) * | 2003-11-21 | 2006-12-20 | 辉瑞产品公司 | 抗生素作为疫苗佐剂的用途 |
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| D SCHIMMEL: "Possibilities for the establishment of pneumonia-free swine herds by immunization and administration of cefquinome", 《BERL MUNCH TIERARZTL WOCHENSCHR》 * |
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| WO2022018576A1 (en) * | 2020-07-20 | 2022-01-27 | Phibro Animal Health Corporation | Controlled release vaccine formulation |
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