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经鼻内接种改良活病毒疫苗向初乳喂养的新生小牛诱导免疫记忆。

Immune memory induced by intranasal vaccination with a modified-live viral vaccine delivered to colostrum fed neonatal calves.

机构信息

Merck Animal Health, De Soto, KS, USA.

VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.

出版信息

Vaccine. 2019 Dec 3;37(51):7455-7462. doi: 10.1016/j.vaccine.2019.09.080. Epub 2019 Oct 4.

Abstract

Bovine respiratory disease (BRD) remains a major health problem despite extensive use of vaccines during the post-weaning period. Apparent vaccine failure is attributed, in part, to primary vaccination during the period of greatest risk for BRD, providing inadequate time for onset of protective immunity. The current study investigated whether intranasal (IN) vaccination of 3-6 week old calves with a modified-live viral (MLV) vaccine induced sufficient immune memory to prevent respiratory disease and accelerate onset of protective immunity 5 months later. Vaccine groups included naïve controls, a single IN vaccination at 3-6 weeks of age, primary IN vaccination at 6 months, and either an IN or subcutaneous (SC) booster vaccination at 6 months (n = 10/group). All calves were challenged with BHV-1 four days after vaccination at 6 months of age. Primary IN vaccination at 6 months did not significantly reduce clinical disease but significantly (P < 0.01) reduced virus shedding. A single IN vaccination at 3-6 weeks of age significantly (P < 0.05) reduced weight loss but did not reduce fever or virus shedding. Both IN and SC booster vaccinations, significantly (P < 0.01) reduced clinical disease but virus shedding was significantly (P < 0.001) reduced only by IN booster vaccination. Reduction in virus shedding was significantly (P < 0.01) greater following booster versus primary IN vaccination at 6 months. All vaccination regimes significantly (P < 0.01) reduced secondary bacterial pneumonia and altered interferon responses relative to naïve controls. Only IN booster vaccination significantly (P < 0.05) increased BHV-1 specific IgA in nasal secretions. These results confirm primary MLV IN vaccination at 3 to 6 weeks of age, when virus neutralizing maternal antibody was present, induced immune memory with a 5 month duration. This immune memory supported rapid onset of protective immunity four days after an IN booster vaccination.

摘要

牛呼吸道疾病(BRD)仍然是一个主要的健康问题,尽管在断奶后期间广泛使用了疫苗。显然,疫苗失败的部分原因是在 BRD 风险最大的时期进行了初级疫苗接种,为保护性免疫的产生提供了不足的时间。本研究调查了在 3-6 周龄的小牛中通过鼻内(IN)接种改良活病毒(MLV)疫苗是否可以诱导足够的免疫记忆,以预防呼吸道疾病并加速 5 个月后保护性免疫的产生。疫苗组包括空白对照组、3-6 周龄时进行一次 IN 接种、6 月龄时进行初级 IN 接种,以及 6 月龄时进行 IN 或皮下(SC)加强接种(每组 10 头)。所有小牛在 6 月龄时接种疫苗后四天都接受了 BHV-1 挑战。6 月龄时进行初级 IN 接种并未显著降低临床疾病,但显著(P < 0.01)降低了病毒脱落。3-6 周龄时进行单次 IN 接种显著(P < 0.05)降低了体重减轻,但并未降低发热或病毒脱落。IN 和 SC 加强接种均显著(P < 0.01)降低了临床疾病,但仅 IN 加强接种显著(P < 0.001)降低了病毒脱落。与 6 月龄时进行初级 IN 接种相比,加强接种后病毒脱落的减少更为显著(P < 0.01)。与空白对照组相比,所有疫苗接种方案均显著(P < 0.01)降低了继发细菌性肺炎,并改变了干扰素反应。仅 IN 加强接种显著(P < 0.05)增加了鼻分泌物中的 BHV-1 特异性 IgA。这些结果证实,在 3 至 6 周龄时,当存在中和病毒的母体抗体时,对 MLV 进行初级 IN 接种可诱导具有 5 个月持续时间的免疫记忆。这种免疫记忆支持在 IN 加强接种后四天快速产生保护性免疫。

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