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猪繁殖与呼吸综合征病毒 2 型活疫苗经肌肉或皮内途径接种的安全性及免针头和针头接种后猪繁殖与呼吸综合征病毒传播的评估。

Safety of PRRSV-2 MLV vaccines administrated via the intramuscular or intradermal route and evaluation of PRRSV transmission upon needle-free and needle delivery.

机构信息

Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Henry Dunant Road, Pathumwan, Bangkok, 10330, Thailand.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.

出版信息

Sci Rep. 2021 Nov 29;11(1):23107. doi: 10.1038/s41598-021-02444-3.

Abstract

Two distinct experiments (Exp) were conducted to evaluate the shedding and efficacy of 2 modified live porcine reproductive and respiratory syndrome virus (PRRSV) type 2 vaccines (MLV) when administered intramuscularly (IM) or intradermally (ID) (Exp A), and the potential of PRRSV transmission using a needle-free device (Exp B). One-hundred fifty-four, 3-week-old castrated-male, pigs were procured from a PRRSV-free herd. In Exp A, 112 pigs were randomly allocated into 4 groups of 21 pigs including IM/Ingelvac MLV (G1), IM/Prime Pac (G2), ID/Prime Pac (G3), and non-vaccination (G4). Twenty-eight remaining pigs were served as non-vaccination, age-matched sentinel pigs. G1 was IM vaccinated once with Ingelvac PRRS MLV (Ing) (Boehringer Ingelheim, Germany). G2 and G3 were IM and ID vaccinated once with a different MLV, Prime Pac PRRS (PP) (MSD Animal Health, The Netherlands), respectively. Following vaccination, an antibody response, IFN-γ-SC, and IL-10 secretion in supernatants of stimulated PBMC were monitored. Sera, tonsils, nasal swabs, bronchoalveolar lavage, urines, and feces were collected from 3 vaccinated pigs each week to 42 days post-vaccination (DPV) and assayed for the presence of PRRSV using virus isolation and qPCR. Age-matched sentinel pigs were used to evaluate the transmission of vaccine viruses and were introduced into vaccinated groups from 0 to 42 DPV. Seroconversion was monitored. In Exp B, 42 pigs were randomly allocated into 5 groups of 3 pigs each including IM/High (T1), ID/High (T2), IM/Low (T3), ID/Low (T4), and NoChal. Twenty-seven remaining pigs were left as non-challenge, age-matched sentinel pigs. The T1 and T2, and T3 and T4 groups were intranasally challenged at approximately 26 days of age with HP-PRRSV-2 at high (10) and low (10 TCID/ml) doses, respectively. At 7 days post-challenge, at the time of the highest viremia levels of HP-PRRSV-2, T1 and T2, and T3 and T4 groups were IM and ID injected with Diluvac Forte using needles and a need-less device (IDAL 3G, MSD Animal Health, The Netherlands), respectively. Same needles or needle-less devices were used to inject the same volume of Diluvac Forte into sentinel pigs. Seroconversion of sentinels was evaluated. The results demonstrated that PP vaccinated groups (G2 and G3), regardless of the route of vaccination, had ELISA response significantly lower than G1 at 7 and 14 DPV. PP-vaccinated groups (G2 and G3) had significantly higher IFN-γ-SC and lower IL-10 secretion compared to the Ing-vaccinated group (G1). The two different MLV when administered intramuscularly demonstrated the difference in virus distribution and shedding patterns. PP-vaccinated pigs had significantly shortened viremia than the Ing-vaccinated pigs. However, ID-vaccinated pigs had lower virus distribution in organs and body fluids without virus shedding to sentinel pigs. In Exp B, regardless of the challenge dose, sentinel pigs intradermally injected with the same needle-less device used to inject challenged pigs displayed no seroconversion. In contrast, sentinel pigs intramuscularly injected with the same needle used to inject challenged pigs displayed seroconversion. The results demonstrated the transmission of PRRSV by using a needle, but not by using a needle-less device. In conclusion, our results demonstrated that ID vaccination might represent an alternative to improve vaccine efficacy and safety, and may be able to reduce the shedding of vaccine viruses and reduce the iatrogenic transfer of pathogens between animals with shared needles.

摘要

两项独立实验(Exp)旨在评估两种改良的猪繁殖与呼吸综合征病毒(PRRSV)2 型活疫苗(MLV)经肌肉内(IM)或皮内(ID)接种时的脱落和效力(Exp A),以及使用无针设备(Exp B)传播 PRRSV 的潜力。从 PRRSV 阴性猪群中获得了 154 头 3 周龄去势公猪。在 Exp A 中,将 112 头猪随机分配到包括肌肉内/英格瓦克 PRRS MLV(G1)、肌肉内/Prime Pac(G2)、皮内/Prime Pac(G3)和非疫苗接种(G4)的 4 个组,每组 21 头。其余 28 头猪作为非疫苗接种的、年龄匹配的哨兵猪。G1 肌肉内接种一次英格瓦克 PRRS MLV(Ing)(德国伯林格殷格翰)。G2 和 G3 分别肌肉内和皮内接种一次不同的 MLV,即 Prime Pac PRRS(PP)(荷兰默克动物保健)。接种后,监测外周血单核细胞刺激上清液中的抗体反应、IFN-γ-SC 和 IL-10 分泌。从接种的 3 头猪中每周收集血清、扁桃体、鼻腔拭子、支气管肺泡灌洗液、尿液和粪便,直至接种后 42 天(DPV),并使用病毒分离和 qPCR 检测 PRRSV 的存在。引入年龄匹配的哨兵猪来评估疫苗病毒的传播,并在 0 至 42 DPV 期间将其引入接种组。监测血清转换。在 Exp B 中,将 42 头猪随机分配到包括肌肉内/高(T1)、皮内/高(T2)、肌肉内/低(T3)、皮内/低(T4)和无挑战(NoChal)的 5 个组,每组 3 头。其余 27 头猪作为非挑战、年龄匹配的哨兵猪。在大约 26 日龄时,T1 和 T2 以及 T3 和 T4 组分别用高(10)和低(10 TCID/ml)剂量的 HP-PRRSV-2 经鼻内挑战。在攻毒后 7 天,当 HP-PRRSV-2 的病毒血症水平达到最高时,T1 和 T2 以及 T3 和 T4 组分别用针和无针设备(MSD 动物保健,荷兰 IDAL 3G)肌肉内和皮内注射 Diluvac Forte。用相同的针或无针设备将相同体积的 Diluvac Forte 注射到哨兵猪中。评估哨兵猪的血清转换。结果表明,PP 接种组(G2 和 G3),无论接种途径如何,在 7 和 14 DPV 时的 ELISA 反应均显著低于 G1。与 Ing 接种组(G1)相比,PP 接种组(G2 和 G3)的 IFN-γ-SC 显著升高,IL-10 分泌显著降低。两种不同的 MLV 经肌肉内接种显示出病毒分布和脱落模式的差异。PP 接种猪的病毒血症持续时间明显短于 Ing 接种猪。然而,皮内接种猪的器官和体液中的病毒分布较低,没有向哨兵猪传播病毒。在 Exp B 中,无论挑战剂量如何,用相同的无针设备皮内注射的哨兵猪均未发生血清转换。相比之下,用相同的针肌肉内注射挑战猪的哨兵猪显示出血清转换。结果表明,使用针可以传播 PRRSV,但使用无针设备则不能。总之,我们的结果表明,ID 接种可能是提高疫苗效力和安全性的一种替代方法,并且可能能够减少疫苗病毒的脱落,并减少动物之间通过共享针头传播病原体的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ae/8629989/8cc47b4c938e/41598_2021_2444_Fig1_HTML.jpg

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