Center for Food Animal Health, Department of Animal Sciences, The Ohio State University, 1680 Madison Avenue, Wooster, OH, 44691, USA.
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
J Nanobiotechnology. 2022 Nov 11;20(1):477. doi: 10.1186/s12951-022-01677-2.
Swine influenza A viruses (SwIAVs) pose an economic and pandemic threat, and development of novel effective vaccines is of critical significance. We evaluated the performance of split swine influenza A virus (SwIAV) H1N2 antigens with a plant-derived nanoparticle adjuvant alone (Nano-11) [Nano11-SwIAV] or in combination with the synthetic stimulator of interferon genes (STING) agonist ADU-S100 (NanoS100-SwIAV). Specific pathogen free (SPF) pigs were vaccinated twice via intramuscular (IM) or intradermal (ID) routes and challenged with a virulent heterologous SwIAV H1N1-OH7 virus.
Animals vaccinated IM or ID with NanoS100-SwIAV had significantly increased cross-reactive IgG and IgA titers in serum, nasal secretion and bronchoalveolar lavage fluid at day post challenge 6 (DPC6). Furthermore, NanoS100-SwIAV ID vaccinates, even at half the vaccine dose compared to their IM vaccinated counterparts, had significantly increased frequencies of CXCL10 myeloid cells in the tracheobronchial lymph nodes (TBLN), and IFNγ effector memory T-helper/memory cells, IL-17A total T-helper/memory cells, central and effector memory T-helper/memory cells, IL-17A total cytotoxic T-lymphocytes (CTLs), and early effector CTLs in blood compared with the Nano11-SwIAV group demonstrating a potential dose-sparing effect and induction of a strong IL-17A T-helper/memory (Th17) response in the periphery. However, the frequencies of IFNγ late effector CTLs and effector memory T-helper/memory cells, IL-17A total CTLs, late effector CTLs, and CXCL10 myeloid cells in blood, as well as lung CXCL10 plasmacytoid dendritic cells were increased in NanoS100-SwIAV IM vaccinated pigs. Increased expression of IL-4 and IL-6 mRNA was observed in TBLN of Nano-11 based IM vaccinates following challenge. Furthermore, the challenge virus load in the lungs and nasal passage was undetectable in NanoS100-SwIAV IM vaccinates by DPC6 along with reduced macroscopic lung lesions and significantly higher virus neutralization titers in lungs at DPC6. However, NanoS100-SwIAV ID vaccinates exhibited significant reduction of challenge virus titers in nasal passages and a remarkable reduction of challenge virus in lungs.
Despite vast genetic difference (77% HA gene identity) between the H1N2 and H1N1 SwIAV, the NanoS100 adjuvanted vaccine elicited cross protective cell mediated immune responses, suggesting the potential role of this combination adjuvant in inducing cross-protective immunity in pigs.
猪流感病毒（SwIAV）构成了经济和大流行威胁，因此开发新型有效的疫苗至关重要。我们评估了具有植物衍生纳米颗粒佐剂的分离猪流感 A 病毒（SwIAV）H1N2 抗原（Nano-11）[Nano11-SwIAV]或与合成干扰素基因刺激物（STING）激动剂 ADU-S100（NanoS100-SwIAV）联合使用的性能。无特定病原体（SPF）猪通过肌内（IM）或皮内（ID）途径两次接种疫苗，并使用具有高毒力的异源 SwIAV H1N1-OH7 病毒进行攻毒。
在攻毒后第 6 天（DPC6），通过 IM 或 ID 接种 NanoS100-SwIAV 的动物的血清、鼻分泌物和支气管肺泡灌洗液中的交叉反应性 IgG 和 IgA 滴度显著增加。此外，与 IM 接种的对照相比，即使 Nanos100-SwIAV ID 接种的疫苗剂量减半，其气管支气管淋巴结（TBLN）中的 CXCL10 髓样细胞以及血液中的 IFNγ效应记忆 T-辅助/记忆细胞、IL-17A 总 T-辅助/记忆细胞、中央和效应记忆 T-辅助/记忆细胞、IL-17A 总细胞毒性 T 淋巴细胞（CTL）和早期效应 CTL 的频率也显著增加，表明存在潜在的剂量节省效应，并在外周诱导强烈的 IL-17A T 辅助/记忆（Th17）反应。然而，在 Nanos100-SwIAV IM 接种的猪中，血液中 IFNγ晚期效应 CTL 和效应记忆 T-辅助/记忆细胞、IL-17A 总 CTL、晚期效应 CTL 和 CXCL10 髓样细胞以及肺部 CXCL10 浆细胞样树突状细胞的频率增加。在挑战后，Nano-11 基于 IM 接种的 TBLN 中观察到 IL-4 和 IL-6 mRNA 的表达增加。此外，NanoS100-SwIAV IM 接种的猪在 DPC6 时肺部和鼻腔中的攻毒病毒载量不可检测，同时肺部宏观病变减少，DPC6 时肺部的病毒中和滴度显著升高。然而，NanoS100-SwIAV ID 接种的猪在鼻腔中的攻毒病毒滴度显著降低，肺部中的攻毒病毒显著减少。
尽管 H1N2 和 H1N1 SwIAV 之间存在巨大的遗传差异（HA 基因同一性为 77%），但 NanoS100 佐剂疫苗诱导了交叉保护的细胞免疫反应，这表明该联合佐剂在诱导猪的交叉保护免疫方面具有潜在作用。
