Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH, United States.
Department of Veterinary Preventive Medicine, Wooster, OH, United States.
Front Immunol. 2021 Mar 4;12:584299. doi: 10.3389/fimmu.2021.584299. eCollection 2021.
Parenteral administration of killed/inactivated swine influenza A virus (SwIAV) vaccine in weaned piglets provides variable levels of immunity due to the presence of preexisting virus specific maternal derived antibodies (MDA). To overcome the effect of MDA on SwIAV vaccine in piglets, we developed an intranasal deliverable killed SwIAV antigen (KAg) encapsulated chitosan nanoparticles called chitosan-based NPs encapsulating KAg (CS NPs-KAg) vaccine. Further, to target the candidate vaccine to dendritic cells and macrophages which express mannose receptor, we conjugated mannose to chitosan (mCS) and formulated KAg encapsulated mCS nanoparticles called mannosylated chitosan-based NPs encapsulating KAg (mCS NPs-KAg) vaccine. In MDA-positive piglets, prime-boost intranasal inoculation of mCS NPs-KAg vaccine elicited enhanced homologous (H1N2-OH10), heterologous (H1N1-OH7), and heterosubtypic (H3N2-OH4) influenza virus-specific secretory IgA (sIgA) antibody response in nasal passage compared to CS NPs-KAg vaccinates. In vaccinated upon challenged with a heterologous SwIAV H1N1, both mCS NPs-KAg and CS NPs-KAg vaccinates augmented H1N2-OH10, H1N1-OH7, and H3N2-OH4 virus-specific sIgA antibody responses in nasal swab, lung lysate, and bronchoalveolar lavage (BAL) fluid; and IgG antibody levels in lung lysate and BAL fluid samples. Whereas, the multivalent commercial inactivated SwIAV vaccine delivered intramuscularly increased serum IgG antibody response. In mCS NPs-KAg and CS NPs-KAg vaccinates increased H1N2-OH10 but not H1N1-OH7 and H3N2-OH4-specific serum hemagglutination inhibition titers were observed. Additionally, mCS NPs-KAg vaccine increased specific recall lymphocyte proliferation and cytokines IL-4, IL-10, and IFNγ gene expression compared to CS NPs-KAg and commercial SwIAV vaccinates in tracheobronchial lymph nodes. Consistent with the immune response both mCS NPs-KAg and CS NPs-KAg vaccinates cleared the challenge H1N1-OH7 virus load in upper and lower respiratory tract more efficiently when compared to commercial vaccine. The virus clearance was associated with reduced gross lung lesions. Overall, mCS NP-KAg vaccine intranasal immunization in MDA-positive pigs induced a robust cross-reactive immunity and offered protection against influenza virus.
经口给予已杀死/灭活的猪流感 A 病毒(SwIAV)疫苗会在断奶仔猪中产生可变水平的免疫,这是由于存在预先存在的病毒特异性母体衍生抗体(MDA)。为了克服 MDA 对仔猪中 SwIAV 疫苗的影响,我们开发了一种可经鼻给予的壳聚糖纳米颗粒包裹的已杀死 SwIAV 抗原(KAg),称为壳聚糖基纳米颗粒包裹 KAg(CS NPs-KAg)疫苗。此外,为了将候选疫苗靶向表达甘露糖受体的树突状细胞和巨噬细胞,我们将甘露糖与壳聚糖(mCS)缀合,并制定了壳聚糖基纳米颗粒包裹 KAg(mCS NPs-KAg)疫苗。在 MDA 阳性的仔猪中,经鼻接种 mCS NPs-KAg 疫苗进行初免-加强免疫,可引起鼻道中增强的同源(H1N2-OH10)、异源(H1N1-OH7)和异亚种(H3N2-OH4)流感病毒特异性分泌型 IgA(sIgA)抗体反应,而 CS NPs-KAg 疫苗则不能。在接种疫苗后用异源 SwIAV H1N1 进行攻毒,mCS NPs-KAg 和 CS NPs-KAg 疫苗均增强了 H1N2-OH10、H1N1-OH7 和 H3N2-OH4 病毒特异性 sIgA 抗体反应,在鼻拭子、肺裂解物和支气管肺泡灌洗液(BAL)中;并且在肺裂解物和 BAL 样本中增加了 IgG 抗体水平。而肌肉内接种多价市售 SwIAV 灭活疫苗可增加血清 IgG 抗体反应。在 mCS NPs-KAg 和 CS NPs-KAg 疫苗接种中,观察到增强的 H1N2-OH10 但没有 H1N1-OH7 和 H3N2-OH4 特异性血清血凝抑制滴度。此外,与 CS NPs-KAg 和市售 SwIAV 疫苗相比,mCS NPs-KAg 疫苗增加了气管支气管淋巴结中特定的回忆性淋巴细胞增殖和细胞因子 IL-4、IL-10 和 IFNγ 基因表达。与免疫反应一致,与市售疫苗相比,mCS NPs-KAg 和 CS NPs-KAg 疫苗接种更有效地清除了上呼吸道和下呼吸道中的挑战 H1N1-OH7 病毒载量。病毒清除与肺部大体病变减少有关。总的来说,mCS NP-KAg 疫苗经鼻免疫接种 MDA 阳性猪可诱导出强大的交叉反应性免疫,并提供对流感病毒的保护。
Vaccine. 2017-2-22
Vet Microbiol. 2019-8-28
Front Cell Infect Microbiol. 2024
Immunooncol Technol. 2023-6-28
Int J Nanomedicine. 2020-2-3
Immunol Lett. 2019-10-25
Iran J Basic Med Sci. 2019-4