当涉及到预防与新城疫病毒(NDV)感染相关的临床症状和死亡率时,疫苗接种非常有效。然而,最近的证据证明,正在出现更多的高毒力菌株,它们绕过现有的免疫保护,对全球家禽业构成严重威胁。这里,一种新型的获救腺病毒5共表达的鸡粒细胞单核细胞集落刺激因子(ChGM-CSF)生物佐剂和C22-血凝素-神经氨酸酶(HN)增强了鸡的免疫遗传抗性,从而提高了关键的新一代疫苗在体外和体内的免疫效力.因此,重组腺病毒(rAdv)-ChGM-CSF-HN免疫鸡的血凝抑制(HI)滴度(log2)更大,更持久,和比LaSota和rAdv-HN接种的鸟类更持久的NDV特异性抗体。此外,在rAdv-ChGM-CSF-HN接种后,体液和适应性免疫条件被证明是和谐的,并且均匀地增强了α干扰素(IFN-α)的表达,IFN-β,IFN-γ,白细胞介素-1β(IL-1β),IL-2、IL-16、IL-18和IL-22。挑战后,控制挑战(CC),野生型腺病毒(WTAdv),rAdv-ChGM-CSF组出现了独特的NDV临床表现,显著的病毒脱落,高组织病毒载量,总体和微观病变,7天内死亡率为100%。LaSota,rAdv-HN,rAdv-ChGM-CSF-HN组均健康,生存率为100%。rAdv-ChGM-CSF-HN组在攻击后5天(dpc)迅速调节并停止病毒脱落,并且组织病毒载量低于所有组。因此,ChGM-CSF的抗病毒活性在面临挑战时提供了强大的免疫保护,并令人信服地减少了病毒复制.我们先进的创新理念,将ChGM-CSF与田间循环菌株表位相结合,可能会导致保险箱的发展,基因型匹配,可以在全球根除这种疾病的通用转基因疫苗,减少贫困和粮食不安全。重要性我们研究了开发的功能性合成重组腺病毒的生物学特性,显示出高度的安全性,热稳定性,和遗传稳定性达20代。通过体外和体内测试证明,拟议疫苗的免疫原性,它使用由甘氨酸和丝氨酸支持的ThoseaAsigna病毒衣壳蛋白的T2A肽,有助于高效地生成多顺反子矢量,能够在rAdv-ChGM-CSF-HN中表达两种功能蛋白,优于同类疫苗。此外,腺病毒可用于生产与毒力场循环菌株表位相匹配的疫苗。因为在动物中没有检测到预先存在的人类腺病毒免疫,腺病毒疫苗的效力看起来很有希望。此外,它确保活载体不携带编码卡那霉素抗生素的抗性基因。因此,经过生物学改进的人重组腺病毒疫苗是有益且重要的。
When it comes to the prevention of clinical signs and mortality associated with infection of the Newcastle disease virus (NDV), vaccination has been very effective. However, recent evidence has proven that more highly virulent strains are emerging that bypass existing immune protection and pose a serious threat to the global poultry industry. Here, a novel rescued adenovirus 5-coexpressed chicken granulocyte monocyte colony-stimulating factor (ChGM-CSF) bio-adjuvant and C22-hemagglutinin-neuraminidase (HN) boosted chickens\' immunological genetic resistance and thus improved the immunological effectiveness of the critical new-generation vaccine in vitro and in vivo. Accordingly, the hemagglutination inhibition (HI) titers (log2) of the recombinant adenovirus (rAdv)-ChGM-CSF-HN-immunized chickens had greater, more persistent, and longer-lasting NDV-specific antibodies than the La Sota and rAdv-HN-inoculated birds. Moreover, humoral and adaptive immunological conditions were shown to be in harmony after rAdv-ChGM-CSF-HN inoculation and uniformly enhanced the expression of alpha interferon (IFN-α), IFN-β, IFN-γ, interleukin-1β (IL-1β), IL-2, IL-16, IL-18, and IL-22. Postchallenge, the control challenge (CC), wild-type adenovirus (wtAdv), and rAdv-ChGM-CSF groups developed unique NDV clinical manifestations, significant viral shedding, high tissue viral loads, gross and microscopic lesions, and 100% mortality within 7 days. The La Sota, rAdv-HN, and rAdv-ChGM-CSF-HN groups were healthy and had 100% survival rates. The rAdv-ChGM-CSF-HN group swiftly regulated and stopped viral shedding and had lower tissue viral loads than all groups at 5 days postchallenge (dpc). Thus, the antiviral activity of ChGM-CSF offered robust immune protection in the face of challenge and reduced viral replication convincingly. Our advance innovation concepts, combining ChGM-CSF with a field-circulating strain epitope, could lead to the development of a safe, genotype-matched, universal transgenic vaccine that could eradicate the disease globally, reducing poverty and food insecurity. IMPORTANCE We studied the biological characterization of the developed functional synthetic recombinant adenoviruses, which showed a high degree of safety, thermostability, and genetic stability for up to 20 passages. It was demonstrated through both in vitro and in vivo testing that the immunogenicity of the proposed vaccine, which uses the T2A peptide from the Thosea asigna virus capsid protein supported by glycine and serine, helps with efficiency to generate a multicistronic vector, enables expression of two functional proteins in rAdv-ChGM-CSF-HN, and is superior to that of comparable vaccines. Additionally, adenovirus can be used to produce vaccines matching the virulent field-circulating strain epitope. Because there is no preexisting human adenoviral immunity detected in animals, the potency of adenoviral vaccines looks promising. Also, it ensures that the living vector does not carry the resistance gene that codes for the kanamycin antibiotic. Accordingly, a human recombinant adenoviral vaccine that has undergone biological improvements is beneficial and important.