犬场三种传染病的免疫程序及其中药佐剂的研究和应用
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摘要
犬瘟热、犬细小病毒病和犬传染性肝炎是严重危害犬业的3种重要传染病。由于这3种传染病都是病毒性传染病,预防接种是控制其发生的重要措施。制定科学合理的免疫程序至关重要,基础抗体水平、幼犬首免日龄、疫苗和剂量等因素均直接影响防控效果。西岗犬场是公安部南京警犬研究所社会化养犬基地之一,目前执行《警犬疾病防治工作规则》所规定的免疫程序。这些程序是否科学合理?本研究进行了初步探讨。本研究系统测定了成年犬常规免疫后血清犬瘟热病毒(CDV)抗体、犬细小病毒(CPV)抗体、犬腺病毒(CAV)抗体效价及外周血白细胞的变化,首免不同日龄、首免不同剂量、首免不同来源疫苗对幼犬3种血清抗体效价的影响,中药佐剂对免疫幼犬3种血清抗体效价和血清细胞因子IFN-γ、IL-2、IL-4和IL-10含量的影响。本研究的目的,旨在找出最佳首免日龄、剂量、疫苗及佐剂,为制定科学合理的免疫程序’、提高3种传染病的防控效果提供理论依据。试验分为以下六个部分：
试验一、成年犬常规免疫后3种抗体效价及白细胞的变化为验证成年犬3种疫苗常规预防接种的效果和基础抗体水平、性别及年龄对体液免疫的影响,随机选择青年母犬5头(Ⅰ)、老年公犬4头(Ⅱ)、青年公犬4头(Ⅲ),均肌肉注射辉瑞四联苗1头份,分别于免疫前(D0)和免疫后第15天(D15)、1个月(M,)、3个月(M,)、6个月(M6)、9个月(M8)采血测定CDV抗体、CPV抗体、CAV抗体、白细胞计数及分类的变化。结果显示,CDV抗体,各组犬在各时间点无显著差异,全年呈高—低—高的态势；CPV抗体,3组在全年呈高—低—高—低的态势,老年公犬在4个时间点显著低于其余2组；CAV抗体,在全年呈高—低—高—低的态势,青年公犬在M。显著低于其余2组。青年母犬在接种前3种抗体均处于较高水平；白细胞总数,青年母犬在D,5上升幅度大,显著高于其余2组；3组在各时间点的白细胞分类无显著差异。结果表明,按照《警犬疾病防治工作条例》对成年犬每年例行一次免疫接种是可行、有效的,老年犬免疫记忆应答保存完整,青年母犬的抗体水平较高,在拟定新生仔犬免疫程序时应考虑母源抗体水平。
试验二、幼犬首免日龄对血清抗体效价的影响为验证本场执行的幼犬45日龄首免是否为最适宜的时间,随机选择35日龄(Ⅰ组)、40日龄(Ⅱ组)、50日龄(Ⅲ组)、45日龄(对照组,C)幼犬各4头,均用犬瘟热-细小病毒二联苗免疫,首免后第14、28天分别用英特威四联活疫苗、辉瑞四联苗重复免疫。分别于首免前(D0)、首免后第7天(D7)、14天(D14)、21天(D21)、28天(D28)、35天(D35)、42天(D42)采血,测定血清CDV抗体、CPV抗体和CAV抗体的变化。结果表明,CDV抗体,大幅上升的时间点随着日龄的增长而逐步提前,母源抗体水平与幼犬免疫后抗体的增幅成反比,以50日龄首免最好,其次是45日龄；CPV抗体,45日龄首免最好,40日龄次之；CAV抗体,35日龄首免最好,45日龄次之。综合考虑以45日龄首免为宜。
试验三、幼犬首免剂量对血清抗体效价的影响为寻找幼犬首免疫苗的最佳剂量,选择45日龄仔犬16头随机分为4组,每组4头,均用英特威犬瘟热-细小病毒二联活疫苗分别按0.5头份(Ⅰ组)、1.5头份(Ⅱ组)、2.0头份(Ⅲ组)、1头份(对照组,C)首免,首免后第14、28天分别用英特威四联苗、辉瑞四联苗二免、三免,于免疫前(D0)和免疫后第7天(D7)、14天(D14)、21天(D21)、28天(D28)、35天(D35)、42天(D42)采血,测定血清CDV抗体、CPV抗体和CAV抗体的变化。结果显示,CDV抗体,0.5头份组在D7即开始上升,此后5个时间点均处于高位,峰值出现的时间较其它3组为早,峰值增幅最高、达81.41%；CPV抗体,0.5头份组于D14开始上升,比1.5头份组早2周,其后一直保持高水平,峰值时间比1.5头份组早1周；CAV抗体,0.5头份组于D35上升幅度大并达到峰值,增幅33.86%,与2头份组、1.5头份组接近,至D42仍维持在较高水平。以上结果表明,0.5头份为首免最佳剂量。
试验四、不同来源疫苗首免对幼犬血清抗体效价的影响为寻找幼犬首免的最佳疫苗,选择45日龄幼犬16头分为4组,每组4头,分别用五星五联苗(Ⅰ组)、英特威四联苗(Ⅱ组)、辉瑞四联苗(Ⅲ组)、英特威二联苗(C组)首免,首免后第14、28天均用英特威四联苗、辉瑞四联苗二免和三免,分别于免疫前(D0)和首免后第7天(D7)、14天(D14)、21天(D21)、28天(D28)、35天(D35)、42天(D42)采血,测定血清CDV抗体、CPV抗体和CAV抗体的变化。结果显示,CDV抗体,Ⅱ组峰值的增幅最高,为77.85%,其次是C组；CPV抗体,C组峰值最高,增幅56.23%,上升平稳,至D42时仍在高位,其次是Ⅱ组；CAV抗体,Ⅱ组表现最好,峰值及其较D0时的增幅最高(48.67%),其次是Ⅱ组。综合比较,首免以英特威四联苗为佳。
试验五、中药佐剂对免疫幼犬血清抗体效价的影响为探讨中药佐剂的免疫增强作用,选择45日龄仔犬24头,随机分为6组,每组4头,分别为方剂Ⅰ低剂量(Ⅰ L)组、方剂Ⅰ高剂量(Ⅰ H)组、方剂Ⅱ低剂量(Ⅱ L)组、方剂Ⅱ高剂量(Ⅱ H)组、左旋咪唑组(adjuvant control, AC)及疫苗对照(non-adjuvant, NA)组,均用英特威二联苗首免,首免后14天用英特威四联苗二免,首免后28天辉瑞四联苗三免；在每次免疫的同时,4中药方剂组分别颈另侧肌肉注射相应药物1mL,左旋咪唑组口服左旋咪唑片(2.5mg/kg),疫苗对照组不给药。分别于免疫前(D0)及免疫后第7(D,)、14(D14)、21(D21)、28(D28)、35(D35)、42(D42)天,前肢静脉采血,检测血清CDV抗体、CPV抗体、CAV抗体的变化。结果显示,对CDV抗体,方Ⅰ高剂量的增强作用最好,于D,即大幅上升,持续至D42仍处最高,峰值的增幅为82.68%,远高于其余各组,其次是方Ⅱ高剂量组；对CPV抗体,方Ⅰ低剂量的增强作用最好,其次是方Ⅰ高剂量,这两组分别于D14和D28达到峰值,增幅均为36.84%,在D14～D42处于高位；对CAV抗体,方Ⅰ高剂量的增强作用最好,在D28上升幅度大,至D4：达峰值,增幅最高(41.40%),其次是方Ⅱ低剂量。以上结果表明,中药佐剂的免疫增强作用明显,方Ⅰ的效果最好。
试验六、中药佐剂对免疫幼犬细胞因子含量的影响为探讨中药佐剂增强免疫的作用机理,选择45日龄仔犬24头,分组和处理同试验五。分别于免疫前(D0)及免疫后第14(D14)、28(D28)和42(D42)天前肢静脉采血,检测血清IL-2、IFN-γ、IL-4和IL-10含量的变化。结果显示,IL-2含量,方I高、低剂量在D,4,4个中药组在D28和D42均显著高于疫苗对照组(P<0.05),方Ⅱ高剂量组在D28最高,其次为方Ⅰ高剂量组,分别为其D。的380.29%和294.03%；IFN-γ含量,方剂Ⅰ低剂量组在D14、4个中药组在D28、方剂Ⅰ低、高剂量组与方剂Ⅱ低剂量组在D42显著高于疫苗对照组(P<0.05),方Ⅱ高剂量组在D28最高,其次方剂Ⅱ低剂量组在D42,分别为其D0的276.30%和236.35%；IL-4含量,方Ⅰ高剂量在D42最高,显著高于疫苗对照组(P<0.05),为其D。的214.55%,其次为方Ⅱ低组在D14,为其D。的197.5%；IL-10含量,4个中药组在D14、方剂Ⅰ高剂量组与方剂Ⅱ高剂量组在D28和D42显著高于疫苗对照组(P<0.05)。以上结果表明,中药佐剂能显著促进细胞因子的分泌,2个方剂均有较好的效果。
基于以上研究,确定了本场防控仔犬3种传染病的免疫程序为：45日龄用英特威四联苗0.5头份首免,分别间隔2周后用英特威四联苗二免、辉瑞四联苗三免,在每次免疫的同时注射中药佐剂Ⅰ高剂量。通过两年多来的应用,取得了满意的防控效果。
Canine distemper, canine parvovirus disease and infectious canine hepatitis are three kinds of important infectious diseases harming dogs seriously. Because they are viral infectious diseases, the vaccination is the most effective measure to control their occurrence. It is very important to enact scientific and rational immunization programme. Some factors directly affect the effect of prevention and control, such as the level of basic antibody level, the first-vaccination age of young dog, vaccine and dose. Xigang canine farm is one of the socialization canine-feeding farms which belongs to Nanjing Institute of Police dog of the Ministry of Public Security. At present, the canine farm carries out the immunization programme from "the working regulation of disease prevention for police dog". Whether these procedures are reasonable or not? A preliminary investigation was carried out. In this study the determination included the changes of serum canine distemper virus (CDV) antibody, canine parvovirus (CPV) antibody, canine adenovirus (CAV) antibody titers and peripheral white blood cell in adult dogs after routine immunization, the effect of the first-vaccination ages, dose and vaccine from different source on three antibody in puppies, and the effect of Chinese herbal medicinal adjuvant on three antibody titers and serum contents of IFN-γ, IL-2, IL-4and IL-10in puppies. The purpose of this study is to select the optimal first-vaccination age, dose, vaccine and adjuvant, and provide the theoretical evidence for establishing scientific and reasonable immune procedure and improving the preventive effect of three kinds of infectious diseases. The details are divided into six parts as follows:
Experiment1. The changes of three antibody titers and white blood cell in adult dogs after routine immunization In order to validate the effectiveness of routine vaccination in adult dogs and the effect of basic antibody levels, sex and age on humoral immunity. Five young female dogs (Ⅰ), four older male dogs (Ⅱ) and four young male dogs (III) were selected randomly. All dogs in three groups were injected with Pfizer quadruple vaccine,1head-dose per dog respectively. Before vaccination (Do) and on day15(D15), months1(M1),3(M3),6(M6) and9(M9) after vaccination, blood was sampled for determination the changes of CDV antibody, CPV antibody, CAV antibody titers, white blood cell count and classification. The results showed that the CDV antibody, there were no significant differences among all group at all time points, and presented high-low-high tendency in whole year. The CPV antibody, in three groups displayed high-low-high-low tendency in whole year, and in older male dogs were significantly lower than those in other two groups at four time points. The CAV antibody, also presented high-low-high-low tendency in whole year, and in young male dogs on M6was significantly lower than those in other two groups. The three kinds of antibody titers in young female dogs were at higher level. The total white blood cells in young female dogs presented a larger rise on days15after vaccination and was significantly higher than those in other two groups. The leukocyte differential counts had no significant difference among three groups at all time points. These results indicated that it was feasible and effective for adult dogs to carry out one shot immunity per year according to "the working regulation of disease prevention for police dog". In the older dogs had the complete immune memory response. The antibody level in young female dogs was higher,therefore, the level of maternal antibody should be considered in immune programme in newly born puppies.
Experiment2. Effect of first-vaccination age on serum antibody titers of puppy In order to verify whether45-day-old is the most suitable time of first vaccination of puppy or not, the35-day-old (Ⅰ),40-day-old (Ⅱ),50-day-old (Ⅲ) and45-day-old (control, C) dogs,4dogs in each group, were randomly selected and vaccinated with canine distemper-canine parvovirus bivalent vaccine. The re-vaccinations were performed on14and28days after the first vaccination with Intervet quadruple vaccine and Pfizer quadruple vaccine respectively. Before vaccination (Do) and on days7(D7),14(D]4),21(D2)),28(D28),35(D35) and42(D42) after the first vaccination, the blood was sampled for determinating the changes of CDV antibody, CPV antibody and CAV antibody titers. The results showed that CDV antibody, the time points with big extent rise were gradually advanced along with the increasing of age, there was an inverse ratio between the maternal antibody level and the rise extent of antibody on puppy after vaccination, and the first vaccination at50-day-old was best, at45-day-old, better. For CPV antibody, first vaccination at45-day-old was best, at40-day-old, secondary. For CAV antibody, first vaccination at35-day-old was best, at45-day-old, next. In general consider45-day-old was reasonable first-vaccination age.
Experiment3. Effect of first-vaccination dose on serum antibody titers of puppy In order to select out the optimal first vaccination dose, sixteen45-day-old puppies were randomly assigned into four groups,4puppies each group and vaccinated with Intervet bivalent vaccine respectively at0.5head-dose (Ⅰ),1.5head-dose (Ⅱ),2.0head-dose (Ⅲ) and1.0head-dose (C), repeated vaccination on days14and28after the first vaccination respectively with Intervet quadruple vaccine and Pfizer quadruple vaccine. Before vaccination (Do) and on days7(D7),14(D14),21(D21),28(D28),35(D35) and42(D42) after the first vaccination, the blood was sampled for determinating the change of serum CDV antibody, CPV antibody and CAV antibody. The results showed that CDV antibody, in0.5head-dose group began to increase on D7and always kept at a high level at the next5time points; the peak value came out earlier than those in other3groups and was higher than those in other3groups reaching81.41%. The CPV antibody, in0.5head-dose group started to increase on D14, which was earlier2weeks than1.5head-dose group, subsequently sustained at high level and the peak value was earlier one week than in1.5head-dose group. The CAV antibody, in0.5head-dose group on D35elevated significantly and reached the peak value with a rise extent of33.86%being close to those in2.0head-dose and1.5head-dose groups, and o D42sustain higher level. These results suggested that0.5head-dose was the the optimal first-vaccination dose.
Experiment4. Effect of different sources vaccine at first vaccination on serum antibody titer of puppy In order to select out the optimal vaccine for the first vaccination, sixteen45-day-old puppies were randomly assigned into four groups,4puppies each group, vaccinated respectively with Five-star quintavalent vaccine (Ⅰ), Intervet quadruple vaccine (Ⅱ), Pfizer quadruple vaccine (Ⅲ) and Intervet bivalent vaccine (C), and repeated vaccination on days14and28after the first vaccination respectively with Intervet quadruple vaccine and Pfizer quadruple vaccine. Before vaccination (Do) and on days7(D7),14(D14),21(D21),28(D28),35(D35) and42(D42) after the first vaccination, the blood was sampled for determinating the change of serum CDV antibody, CPV antibody and CAV antibody. The results showed that the CDV antibody, the rise extent of peak value in II group was hight arriving77.85%. The next was C group. CPV antibody, the peak value in C group was highest with a rise extent of56.23%and stable ascension, and still sustained at higher level on D42. The next was Ⅱ group. CAV antibody, the peak value and its rise extent in Ⅲ group were highest (48.67%), the second was Ⅱ group. In general comparison, Intervet quadruple vaccine was better in first vaccination.
Experiment5. Effect of Chinese herbal medicinal adjuvant on serum antibody titer of vaccinated puppy In order to study the immunoenhancement of Chinese herbal medicinal adjuvant, twenty-four45-old-day puppies were randomly assigned into6groups (4puppies a group), prescription Ⅰ low dose (Ⅰ L) and high dose (Ⅰ H)group, prescriptions Ⅱ low dose (ⅡL) and high dose (ⅡH) group, levamisole group (adjuvant control, AC) and non-adjuvant control (NA) group. All puppies were vaccinated with Intervet bivalent vaccine, and repeated vaccination on days14and28after the first vaccination respectively with Intervet quadruple vaccine and Pfizer quadruple vaccine. At the same time of every vaccination, puppies in the four Chinese herbal medicine groups were intramuscularly injected1mL of corresponding drug in other side of neck, in AC group, given Ergamisole2.5mg/kg per os, and in NA group not given any drug. Before vaccination (Do) and on days7(D7),14(D14),21(D21),28(D28),35(D35) and42(D42) after first vaccination, blood were sampled from forelimb vein for determination of CDV antibody, CPV antibody and CAV antibody. The results showed that for CDV antibody, the effect of ⅠH was best, which risen sharply from D7, upto D42kept at high level, and the amplification of peak value was82.68%and much higher than the rest groups, the following was ⅡH group. For CPV antibody, the effect of ⅠL was best, the following was ⅠL. This two groups reached peak value respectively on D14and D28, with a amplifications of36.84%and keeping at higher level during D14to D42. For CAV antibody, the effect of ⅠH was best, on D28presentd a larger rise extent and on D42reached peak value with a highest amplification (41.40%), the following was ⅡL group. These results revealed that the Chinese herbal medicinal adjuvant possessed obvious immunoenhancement, and Prescription I expressed a better effect.
Experiment6. Effect of Chinese herbal medicinal adjuvant on content of cytokine in vaccinated puppy In order to study the immunoenhancement mechanism of Chinese herbal medicinal adjuvant, Twenty-four45-day-old puppies were selected and treated similar to test5. Before vaccination (Do) and on days 14(D14),21(D21),28(D28),35(D35) and42(D42) after vaccination, blood were sampled from forelimb vein for determination of the change of serum IL-2, IFN-γ, IL-4and IL-10content. The results showed that IL-2content, in Ⅰ H, ⅠL group on D14and four Chinese herbal medicine groups on D28and D42were significantly higher than those in NA group (P<0.05), in ⅡH group on D28was the highest, the next was ⅠL group and they were280.29%and194.03%of those on Do respectively. IFN-y content, in ⅠL group on D14, four Chinese herbl medicine groups on D28,ⅠL, ⅠH and ⅡL group on D42were significantly higher than those in NA group (P<0.05), in ⅡH group on D28was highest, the following was ⅡL group on D42the two groups made up176.30%and136.35%of those on Do, respectively. IL-4content, in ⅠH group on D42was highest, significantly higher than that in NA group (P<0.05) and it made up114.55%of that on Do, the following was ⅡL group on D14made up97.5%of that on on D0.IL-10content, in the four Chinese herbal medicine groups on D14, ⅠH and ⅡH on D28and D42were significantly higher than those in NA group (P<0.05). All these results revealed that Chinese herbal medicinal adjuvant could significantly promote the secretion of cytokine, and both of two prescriptions possessed better effect.
Based to above research, the immune programme for three infectious diseases of young dog in our farm was decided:the first vaccination at45-days-old with0.5head-dose of Intervet quadruple vaccine, the second with Intervet quadruple vaccine and third with Pfizer quadruple vaccine after2weeks interval. At the same times each vaccination, high dose of Chinese herbal medicinal adjuvant I was injected. By more than two years'application, the satisfactory effect was obtained for three infectious diseases in our farm.
试验一、成年犬常规免疫后3种抗体效价及白细胞的变化为验证成年犬3种疫苗常规预防接种的效果和基础抗体水平、性别及年龄对体液免疫的影响,随机选择青年母犬5头(Ⅰ)、老年公犬4头(Ⅱ)、青年公犬4头(Ⅲ),均肌肉注射辉瑞四联苗1头份,分别于免疫前(D0)和免疫后第15天(D15)、1个月(M,)、3个月(M,)、6个月(M6)、9个月(M8)采血测定CDV抗体、CPV抗体、CAV抗体、白细胞计数及分类的变化。结果显示,CDV抗体,各组犬在各时间点无显著差异,全年呈高—低—高的态势；CPV抗体,3组在全年呈高—低—高—低的态势,老年公犬在4个时间点显著低于其余2组；CAV抗体,在全年呈高—低—高—低的态势,青年公犬在M。显著低于其余2组。青年母犬在接种前3种抗体均处于较高水平；白细胞总数,青年母犬在D,5上升幅度大,显著高于其余2组；3组在各时间点的白细胞分类无显著差异。结果表明,按照《警犬疾病防治工作条例》对成年犬每年例行一次免疫接种是可行、有效的,老年犬免疫记忆应答保存完整,青年母犬的抗体水平较高,在拟定新生仔犬免疫程序时应考虑母源抗体水平。
试验二、幼犬首免日龄对血清抗体效价的影响为验证本场执行的幼犬45日龄首免是否为最适宜的时间,随机选择35日龄(Ⅰ组)、40日龄(Ⅱ组)、50日龄(Ⅲ组)、45日龄(对照组,C)幼犬各4头,均用犬瘟热-细小病毒二联苗免疫,首免后第14、28天分别用英特威四联活疫苗、辉瑞四联苗重复免疫。分别于首免前(D0)、首免后第7天(D7)、14天(D14)、21天(D21)、28天(D28)、35天(D35)、42天(D42)采血,测定血清CDV抗体、CPV抗体和CAV抗体的变化。结果表明,CDV抗体,大幅上升的时间点随着日龄的增长而逐步提前,母源抗体水平与幼犬免疫后抗体的增幅成反比,以50日龄首免最好,其次是45日龄；CPV抗体,45日龄首免最好,40日龄次之；CAV抗体,35日龄首免最好,45日龄次之。综合考虑以45日龄首免为宜。
试验三、幼犬首免剂量对血清抗体效价的影响为寻找幼犬首免疫苗的最佳剂量,选择45日龄仔犬16头随机分为4组,每组4头,均用英特威犬瘟热-细小病毒二联活疫苗分别按0.5头份(Ⅰ组)、1.5头份(Ⅱ组)、2.0头份(Ⅲ组)、1头份(对照组,C)首免,首免后第14、28天分别用英特威四联苗、辉瑞四联苗二免、三免,于免疫前(D0)和免疫后第7天(D7)、14天(D14)、21天(D21)、28天(D28)、35天(D35)、42天(D42)采血,测定血清CDV抗体、CPV抗体和CAV抗体的变化。结果显示,CDV抗体,0.5头份组在D7即开始上升,此后5个时间点均处于高位,峰值出现的时间较其它3组为早,峰值增幅最高、达81.41%；CPV抗体,0.5头份组于D14开始上升,比1.5头份组早2周,其后一直保持高水平,峰值时间比1.5头份组早1周；CAV抗体,0.5头份组于D35上升幅度大并达到峰值,增幅33.86%,与2头份组、1.5头份组接近,至D42仍维持在较高水平。以上结果表明,0.5头份为首免最佳剂量。
试验四、不同来源疫苗首免对幼犬血清抗体效价的影响为寻找幼犬首免的最佳疫苗,选择45日龄幼犬16头分为4组,每组4头,分别用五星五联苗(Ⅰ组)、英特威四联苗(Ⅱ组)、辉瑞四联苗(Ⅲ组)、英特威二联苗(C组)首免,首免后第14、28天均用英特威四联苗、辉瑞四联苗二免和三免,分别于免疫前(D0)和首免后第7天(D7)、14天(D14)、21天(D21)、28天(D28)、35天(D35)、42天(D42)采血,测定血清CDV抗体、CPV抗体和CAV抗体的变化。结果显示,CDV抗体,Ⅱ组峰值的增幅最高,为77.85%,其次是C组；CPV抗体,C组峰值最高,增幅56.23%,上升平稳,至D42时仍在高位,其次是Ⅱ组；CAV抗体,Ⅱ组表现最好,峰值及其较D0时的增幅最高(48.67%),其次是Ⅱ组。综合比较,首免以英特威四联苗为佳。
试验五、中药佐剂对免疫幼犬血清抗体效价的影响为探讨中药佐剂的免疫增强作用,选择45日龄仔犬24头,随机分为6组,每组4头,分别为方剂Ⅰ低剂量(Ⅰ L)组、方剂Ⅰ高剂量(Ⅰ H)组、方剂Ⅱ低剂量(Ⅱ L)组、方剂Ⅱ高剂量(Ⅱ H)组、左旋咪唑组(adjuvant control, AC)及疫苗对照(non-adjuvant, NA)组,均用英特威二联苗首免,首免后14天用英特威四联苗二免,首免后28天辉瑞四联苗三免；在每次免疫的同时,4中药方剂组分别颈另侧肌肉注射相应药物1mL,左旋咪唑组口服左旋咪唑片(2.5mg/kg),疫苗对照组不给药。分别于免疫前(D0)及免疫后第7(D,)、14(D14)、21(D21)、28(D28)、35(D35)、42(D42)天,前肢静脉采血,检测血清CDV抗体、CPV抗体、CAV抗体的变化。结果显示,对CDV抗体,方Ⅰ高剂量的增强作用最好,于D,即大幅上升,持续至D42仍处最高,峰值的增幅为82.68%,远高于其余各组,其次是方Ⅱ高剂量组；对CPV抗体,方Ⅰ低剂量的增强作用最好,其次是方Ⅰ高剂量,这两组分别于D14和D28达到峰值,增幅均为36.84%,在D14～D42处于高位；对CAV抗体,方Ⅰ高剂量的增强作用最好,在D28上升幅度大,至D4：达峰值,增幅最高(41.40%),其次是方Ⅱ低剂量。以上结果表明,中药佐剂的免疫增强作用明显,方Ⅰ的效果最好。
试验六、中药佐剂对免疫幼犬细胞因子含量的影响为探讨中药佐剂增强免疫的作用机理,选择45日龄仔犬24头,分组和处理同试验五。分别于免疫前(D0)及免疫后第14(D14)、28(D28)和42(D42)天前肢静脉采血,检测血清IL-2、IFN-γ、IL-4和IL-10含量的变化。结果显示,IL-2含量,方I高、低剂量在D,4,4个中药组在D28和D42均显著高于疫苗对照组(P<0.05),方Ⅱ高剂量组在D28最高,其次为方Ⅰ高剂量组,分别为其D。的380.29%和294.03%；IFN-γ含量,方剂Ⅰ低剂量组在D14、4个中药组在D28、方剂Ⅰ低、高剂量组与方剂Ⅱ低剂量组在D42显著高于疫苗对照组(P<0.05),方Ⅱ高剂量组在D28最高,其次方剂Ⅱ低剂量组在D42,分别为其D0的276.30%和236.35%；IL-4含量,方Ⅰ高剂量在D42最高,显著高于疫苗对照组(P<0.05),为其D。的214.55%,其次为方Ⅱ低组在D14,为其D。的197.5%；IL-10含量,4个中药组在D14、方剂Ⅰ高剂量组与方剂Ⅱ高剂量组在D28和D42显著高于疫苗对照组(P<0.05)。以上结果表明,中药佐剂能显著促进细胞因子的分泌,2个方剂均有较好的效果。
基于以上研究,确定了本场防控仔犬3种传染病的免疫程序为：45日龄用英特威四联苗0.5头份首免,分别间隔2周后用英特威四联苗二免、辉瑞四联苗三免,在每次免疫的同时注射中药佐剂Ⅰ高剂量。通过两年多来的应用,取得了满意的防控效果。
Canine distemper, canine parvovirus disease and infectious canine hepatitis are three kinds of important infectious diseases harming dogs seriously. Because they are viral infectious diseases, the vaccination is the most effective measure to control their occurrence. It is very important to enact scientific and rational immunization programme. Some factors directly affect the effect of prevention and control, such as the level of basic antibody level, the first-vaccination age of young dog, vaccine and dose. Xigang canine farm is one of the socialization canine-feeding farms which belongs to Nanjing Institute of Police dog of the Ministry of Public Security. At present, the canine farm carries out the immunization programme from "the working regulation of disease prevention for police dog". Whether these procedures are reasonable or not? A preliminary investigation was carried out. In this study the determination included the changes of serum canine distemper virus (CDV) antibody, canine parvovirus (CPV) antibody, canine adenovirus (CAV) antibody titers and peripheral white blood cell in adult dogs after routine immunization, the effect of the first-vaccination ages, dose and vaccine from different source on three antibody in puppies, and the effect of Chinese herbal medicinal adjuvant on three antibody titers and serum contents of IFN-γ, IL-2, IL-4and IL-10in puppies. The purpose of this study is to select the optimal first-vaccination age, dose, vaccine and adjuvant, and provide the theoretical evidence for establishing scientific and reasonable immune procedure and improving the preventive effect of three kinds of infectious diseases. The details are divided into six parts as follows:
Experiment1. The changes of three antibody titers and white blood cell in adult dogs after routine immunization In order to validate the effectiveness of routine vaccination in adult dogs and the effect of basic antibody levels, sex and age on humoral immunity. Five young female dogs (Ⅰ), four older male dogs (Ⅱ) and four young male dogs (III) were selected randomly. All dogs in three groups were injected with Pfizer quadruple vaccine,1head-dose per dog respectively. Before vaccination (Do) and on day15(D15), months1(M1),3(M3),6(M6) and9(M9) after vaccination, blood was sampled for determination the changes of CDV antibody, CPV antibody, CAV antibody titers, white blood cell count and classification. The results showed that the CDV antibody, there were no significant differences among all group at all time points, and presented high-low-high tendency in whole year. The CPV antibody, in three groups displayed high-low-high-low tendency in whole year, and in older male dogs were significantly lower than those in other two groups at four time points. The CAV antibody, also presented high-low-high-low tendency in whole year, and in young male dogs on M6was significantly lower than those in other two groups. The three kinds of antibody titers in young female dogs were at higher level. The total white blood cells in young female dogs presented a larger rise on days15after vaccination and was significantly higher than those in other two groups. The leukocyte differential counts had no significant difference among three groups at all time points. These results indicated that it was feasible and effective for adult dogs to carry out one shot immunity per year according to "the working regulation of disease prevention for police dog". In the older dogs had the complete immune memory response. The antibody level in young female dogs was higher,therefore, the level of maternal antibody should be considered in immune programme in newly born puppies.
Experiment2. Effect of first-vaccination age on serum antibody titers of puppy In order to verify whether45-day-old is the most suitable time of first vaccination of puppy or not, the35-day-old (Ⅰ),40-day-old (Ⅱ),50-day-old (Ⅲ) and45-day-old (control, C) dogs,4dogs in each group, were randomly selected and vaccinated with canine distemper-canine parvovirus bivalent vaccine. The re-vaccinations were performed on14and28days after the first vaccination with Intervet quadruple vaccine and Pfizer quadruple vaccine respectively. Before vaccination (Do) and on days7(D7),14(D]4),21(D2)),28(D28),35(D35) and42(D42) after the first vaccination, the blood was sampled for determinating the changes of CDV antibody, CPV antibody and CAV antibody titers. The results showed that CDV antibody, the time points with big extent rise were gradually advanced along with the increasing of age, there was an inverse ratio between the maternal antibody level and the rise extent of antibody on puppy after vaccination, and the first vaccination at50-day-old was best, at45-day-old, better. For CPV antibody, first vaccination at45-day-old was best, at40-day-old, secondary. For CAV antibody, first vaccination at35-day-old was best, at45-day-old, next. In general consider45-day-old was reasonable first-vaccination age.
Experiment3. Effect of first-vaccination dose on serum antibody titers of puppy In order to select out the optimal first vaccination dose, sixteen45-day-old puppies were randomly assigned into four groups,4puppies each group and vaccinated with Intervet bivalent vaccine respectively at0.5head-dose (Ⅰ),1.5head-dose (Ⅱ),2.0head-dose (Ⅲ) and1.0head-dose (C), repeated vaccination on days14and28after the first vaccination respectively with Intervet quadruple vaccine and Pfizer quadruple vaccine. Before vaccination (Do) and on days7(D7),14(D14),21(D21),28(D28),35(D35) and42(D42) after the first vaccination, the blood was sampled for determinating the change of serum CDV antibody, CPV antibody and CAV antibody. The results showed that CDV antibody, in0.5head-dose group began to increase on D7and always kept at a high level at the next5time points; the peak value came out earlier than those in other3groups and was higher than those in other3groups reaching81.41%. The CPV antibody, in0.5head-dose group started to increase on D14, which was earlier2weeks than1.5head-dose group, subsequently sustained at high level and the peak value was earlier one week than in1.5head-dose group. The CAV antibody, in0.5head-dose group on D35elevated significantly and reached the peak value with a rise extent of33.86%being close to those in2.0head-dose and1.5head-dose groups, and o D42sustain higher level. These results suggested that0.5head-dose was the the optimal first-vaccination dose.
Experiment4. Effect of different sources vaccine at first vaccination on serum antibody titer of puppy In order to select out the optimal vaccine for the first vaccination, sixteen45-day-old puppies were randomly assigned into four groups,4puppies each group, vaccinated respectively with Five-star quintavalent vaccine (Ⅰ), Intervet quadruple vaccine (Ⅱ), Pfizer quadruple vaccine (Ⅲ) and Intervet bivalent vaccine (C), and repeated vaccination on days14and28after the first vaccination respectively with Intervet quadruple vaccine and Pfizer quadruple vaccine. Before vaccination (Do) and on days7(D7),14(D14),21(D21),28(D28),35(D35) and42(D42) after the first vaccination, the blood was sampled for determinating the change of serum CDV antibody, CPV antibody and CAV antibody. The results showed that the CDV antibody, the rise extent of peak value in II group was hight arriving77.85%. The next was C group. CPV antibody, the peak value in C group was highest with a rise extent of56.23%and stable ascension, and still sustained at higher level on D42. The next was Ⅱ group. CAV antibody, the peak value and its rise extent in Ⅲ group were highest (48.67%), the second was Ⅱ group. In general comparison, Intervet quadruple vaccine was better in first vaccination.
Experiment5. Effect of Chinese herbal medicinal adjuvant on serum antibody titer of vaccinated puppy In order to study the immunoenhancement of Chinese herbal medicinal adjuvant, twenty-four45-old-day puppies were randomly assigned into6groups (4puppies a group), prescription Ⅰ low dose (Ⅰ L) and high dose (Ⅰ H)group, prescriptions Ⅱ low dose (ⅡL) and high dose (ⅡH) group, levamisole group (adjuvant control, AC) and non-adjuvant control (NA) group. All puppies were vaccinated with Intervet bivalent vaccine, and repeated vaccination on days14and28after the first vaccination respectively with Intervet quadruple vaccine and Pfizer quadruple vaccine. At the same time of every vaccination, puppies in the four Chinese herbal medicine groups were intramuscularly injected1mL of corresponding drug in other side of neck, in AC group, given Ergamisole2.5mg/kg per os, and in NA group not given any drug. Before vaccination (Do) and on days7(D7),14(D14),21(D21),28(D28),35(D35) and42(D42) after first vaccination, blood were sampled from forelimb vein for determination of CDV antibody, CPV antibody and CAV antibody. The results showed that for CDV antibody, the effect of ⅠH was best, which risen sharply from D7, upto D42kept at high level, and the amplification of peak value was82.68%and much higher than the rest groups, the following was ⅡH group. For CPV antibody, the effect of ⅠL was best, the following was ⅠL. This two groups reached peak value respectively on D14and D28, with a amplifications of36.84%and keeping at higher level during D14to D42. For CAV antibody, the effect of ⅠH was best, on D28presentd a larger rise extent and on D42reached peak value with a highest amplification (41.40%), the following was ⅡL group. These results revealed that the Chinese herbal medicinal adjuvant possessed obvious immunoenhancement, and Prescription I expressed a better effect.
Experiment6. Effect of Chinese herbal medicinal adjuvant on content of cytokine in vaccinated puppy In order to study the immunoenhancement mechanism of Chinese herbal medicinal adjuvant, Twenty-four45-day-old puppies were selected and treated similar to test5. Before vaccination (Do) and on days 14(D14),21(D21),28(D28),35(D35) and42(D42) after vaccination, blood were sampled from forelimb vein for determination of the change of serum IL-2, IFN-γ, IL-4and IL-10content. The results showed that IL-2content, in Ⅰ H, ⅠL group on D14and four Chinese herbal medicine groups on D28and D42were significantly higher than those in NA group (P<0.05), in ⅡH group on D28was the highest, the next was ⅠL group and they were280.29%and194.03%of those on Do respectively. IFN-y content, in ⅠL group on D14, four Chinese herbl medicine groups on D28,ⅠL, ⅠH and ⅡL group on D42were significantly higher than those in NA group (P<0.05), in ⅡH group on D28was highest, the following was ⅡL group on D42the two groups made up176.30%and136.35%of those on Do, respectively. IL-4content, in ⅠH group on D42was highest, significantly higher than that in NA group (P<0.05) and it made up114.55%of that on Do, the following was ⅡL group on D14made up97.5%of that on on D0.IL-10content, in the four Chinese herbal medicine groups on D14, ⅠH and ⅡH on D28and D42were significantly higher than those in NA group (P<0.05). All these results revealed that Chinese herbal medicinal adjuvant could significantly promote the secretion of cytokine, and both of two prescriptions possessed better effect.
Based to above research, the immune programme for three infectious diseases of young dog in our farm was decided:the first vaccination at45-days-old with0.5head-dose of Intervet quadruple vaccine, the second with Intervet quadruple vaccine and third with Pfizer quadruple vaccine after2weeks interval. At the same times each vaccination, high dose of Chinese herbal medicinal adjuvant I was injected. By more than two years'application, the satisfactory effect was obtained for three infectious diseases in our farm.
引文
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