Wageningen Bioveterinary Research, Wageningen University & Research, P.O. Box 29703, 2502 LS, The Hague, the Netherlands.
Wageningen Bioveterinary Research, Wageningen University & Research, P.O. Box 29703, 2502 LS, The Hague, the Netherlands.
Vet Immunol Immunopathol. 2021 Feb;232:110170. doi: 10.1016/j.vetimm.2020.110170. Epub 2020 Dec 15.
Vaccination of neonatal pigs could be supportive to prevent porcine reproductive and respiratory syndrome virus (PRRSV), which is an important porcine pathogen causing worldwide welfare and health problems in pigs of different age classes. However, neonatal immunity substantially differs to adults, thus different vaccines may be required in neonateal pigs. We examined if the immunogenicity and efficacy of inactivated PRRSV (iPRRSV) vaccines in neonatal pigs could be improved with adjuvants containing oil-in water (O/W) emulsions with or without Toll-like receptor (TLR) agonists and by altering the delivery route from intramuscular (i.m.) to the skin. Three-day-old PRRSV-naïve piglets (n = 54, divided in 6 groups) received a prime vaccination and a booster vaccination four weeks later. The vaccine formulations consisted of different O/W emulsions (Montanide™ ISA28RVG (ISA28)), a squalene in water emulsion (SWE) for i.m. or a Stable Emulsion (SE) with squalene for skin vaccination) and/or a mixture of TLR1/2, 7/8 and 9 agonists (TLRa) combined with iPRRSV strain 07V063. These vaccines were delivered either i.m. (ISA28, SWE, TLRa or SWE + TLRa) or into the skin (skiSE + TLRa) with dissolving microneedle (DMN)-patches. All animals received a challenge with homologous PRRSV three weeks after booster vaccination. Specific antibodies, IFN-γ production and viremia were measured at several time-points after vaccination and/or challenge, while lung pathology was studied at necropsy. After booster vaccination, only ISA28 induced a specific antibody response while a specific T-cell IFN-γ response was generated in the SWE group, that was lower for ISA28, and absent in the other groups. This suggests that prime vaccination in neonates induced a specific immune response after booster vaccination, dependent on the emulsion formulation, but not dependent on the presence of the TLRa or delivery route. Despite the measured immune responses none of the vaccines showed any efficacy. Further research focused on the early immune response in draining lymph nodes is needed to elucidate the potential of TLR agonists in vaccines for neonatal pigs.
对新生仔猪进行疫苗接种可以支持预防猪繁殖与呼吸综合征病毒（PRRSV），这是一种重要的猪病原体，会给不同年龄段的猪造成全球性的福利和健康问题。然而，新生仔猪的免疫功能与成年猪有很大的不同，因此可能需要为新生仔猪提供不同的疫苗。我们研究了在新生仔猪中，使用含有油包水（O/W）乳液的佐剂（含或不含 Toll 样受体（TLR）激动剂）和改变从肌肉内（i.m.）到皮肤的给药途径是否可以提高灭活 PRRSV（iPRRSV）疫苗的免疫原性和效力。将 3 日龄 PRRSV 初免仔猪（n=54，分为 6 组）进行初免接种和 4 周后的加强免疫。疫苗制剂由不同的 O/W 乳液（Montanide™ ISA28RVG（ISA28））、水包油佐剂（SWE）用于 i.m. 接种或含有角鲨烯的稳定乳液（SE）用于皮内接种）和/或 TLR1/2、7/8 和 9 激动剂混合物（TLRa）与 PRRSV 07V063 株联合组成，并分别通过微针（DMN）贴片 i.m.（ISA28、SWE、TLRa 或 SWE+TLRa）或皮内（skiSE+TLRa）给药。所有动物在加强免疫后 3 周接受同源 PRRSV 攻毒。在接种和/或攻毒后的多个时间点测量特异性抗体、IFN-γ产生和病毒血症，同时在剖检时研究肺脏病理学。在加强免疫后，只有 ISA28 诱导了特异性抗体反应，而 SWE 组产生了特异性 T 细胞 IFN-γ反应，但 ISA28 组较低，其他组则没有。这表明初免接种在新生仔猪中诱导了加强免疫后的特异性免疫反应，这取决于乳液制剂，但与 TLRa 的存在或给药途径无关。尽管测量了免疫反应，但没有一种疫苗表现出任何效力。需要进一步研究引流淋巴结中的早期免疫反应，以阐明 TLR 激动剂在新生仔猪疫苗中的潜力。
