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首页> 外文期刊>The American Journal of Tropical Medicine and Hygiene >Plant-Produced Subunit Vaccine Candidates against Yellow Fever Induce Virus Neutralizing Antibodies and Confer Protection against Viral Challenge in Animal Models
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Plant-Produced Subunit Vaccine Candidates against Yellow Fever Induce Virus Neutralizing Antibodies and Confer Protection against Viral Challenge in Animal Models

机译：植物产生的亚单位疫苗候选患者对黄热病诱导病毒中和抗体并赋予动物模型中病毒攻击的保护

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Yellow fever (YF) is a viral disease transmitted by mosquitoes and endemic mostly in South America and Africa with 20-50% fatality. All current licensed YF vaccines, including YF-Vax (R) (Sanofi-Pasteur, Lyon, France) and 17DD-YFV (Bio-Manguinhos, Rio de Janeiro, Brazil), are based on live attenuated virus produced in hens' eggs and have been widely used. The YF vaccines are considered safe and highly effective. However, a recent increase in demand for YF vaccines and reports of rare cases of YF vaccine-associated fatal adverse events have provoked interest in developing a safer YF vaccine that can be easily scaled up to meet this increased global demand. To this point, we have engineered the YF virus envelope protein (YFE) and transiently expressed it in Nicotiana benthamiana as a stand-alone protein (YFE) or as fusion to the bacterial enzyme lichenase (YFE-LicKM). Immunogenicity and challenge studies in mice demonstrated that both YFE and YFE-LicKM elicited virus neutralizing (VN) antibodies and protected over 70% of mice from lethal challenge infection. Furthermore, these two YFE-based vaccine candidates induced VN antibody responses with high serum avidity in nonhuman primates and these VN antibody responses were further enhanced after challenge infection with the 17DD strain of YF virus. These results demonstrate partial protective efficacy in mice of YFE-based subunit vaccines expressed in N. benthamiana. However, their efficacy is inferior to that of the live attenuated 17DD vaccine, indicating that formulation development, such as incorporating a more suitable adjuvant, may be required for product development.
机译：黄热病（yf）是蚊子和流行的病毒疾病，主要是南美洲和非洲的死亡率为20-50％。所有当前许可的YF疫苗，包括YF-VAX（R）（Sanofi-Pasteur，Lyon，France）和17dd-YFV（Bio-Manguinhos，Rio de Janeiro，Brazil）均基于母鸡和鸡蛋生产的活病毒已被广泛使用。 YF疫苗被认为是安全且非常有效的。然而，最近对YF疫苗的需求增加和罕见的YF疫苗相关致命不良事件的报告引起了开发更安全的YF疫苗的兴趣，这可以很容易地扩大，以满足全球需求的增加。为此，我们已经设计了Yf病毒包膜蛋白（YFE），并且在尼古利氏植物果仁南裔人作为单独的蛋白质（YFE）或作为细菌酶Lichenase（YFE-Lickm）的融合，瞬时表达它。小鼠的免疫原性和攻击性研究表明，YFE和YFE-Lickm引发了病毒中和（VN）抗体，并保护了来自致死攻击感染的70％的小鼠。此外，这两种基于YFE的疫苗候选诱导了在非人制灵线中具有高血清亲合力的VN抗体应答，并且在用17dd的Yf病毒进行攻击感染后进一步提高了这些VN抗体应答。这些结果表明了在N型果实疫苗的基于YFE的亚基疫苗小鼠中的部分保护效果。然而，它们的功效不如现场减毒的17dd疫苗的功效，表明制剂发育，例如掺入更合适的佐剂，可以进行产品开发。

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    Tottey Stephen; Shoji Yoko; Jones R. Mark; Chichester Jessica A.; Green Brian J.; Musiychuk Konstantin; Si Huaxin; Manceva Slobodanka D.; Rhee Amy; Shamloul Moneim; Norikane Joey; Guimaraes Rosane C.; Caride Elena; Silva Andrea N. M. R.; Simoes Marisol; Neves Patricia C. C.; Marchevsky Renato; Freire Marcos S.; Streatfield Stephen J.; Yusibov Vidadi;

  • 作者单位

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

    Fiocruz MS Inst Tecnol Imunobiol Biomanguinhos Rio De Janeiro Brazil;

    Fiocruz MS Inst Tecnol Imunobiol Biomanguinhos Rio De Janeiro Brazil;

    Fiocruz MS Inst Tecnol Imunobiol Biomanguinhos Rio De Janeiro Brazil;

    Fiocruz MS Inst Tecnol Imunobiol Biomanguinhos Rio De Janeiro Brazil;

    Fiocruz MS Inst Tecnol Imunobiol Biomanguinhos Rio De Janeiro Brazil;

    Fiocruz MS Inst Tecnol Imunobiol Biomanguinhos Rio De Janeiro Brazil;

    Fiocruz MS Inst Tecnol Imunobiol Biomanguinhos Rio De Janeiro Brazil;

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

    Fraunhofer USA Ctr Mol Biotechnol 9 Innovat Way Suite 200 Newark DE 19711 USA;

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  • 中图分类 地方病学;
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