展示犬瘟热病毒糖蛋白的灭活重组狂犬病病毒可诱导针对两种病原体的保护性免疫。
Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens.
作者信息
da Fontoura Budaszewski Renata, Hudacek Andrew, Sawatsky Bevan, Krämer Beate, Yin Xiangping, Schnell Matthias J, von Messling Veronika
机构信息
Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Veterinary Medicine Division, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany.
出版信息
J Virol. 2017 Mar 29;91(8). doi: 10.1128/JVI.02077-16. Print 2017 Apr 15.
The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains. Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received recombinant rabies viruses carrying only the CDV attachment protein according to the same immunization scheme died. Irrespective of the CDV antigens used, all animals developed protective titers against rabies virus, illustrating that a bivalent rabies virus-based vaccine against CDV induces protective immune responses against both pathogens.
多价疫苗的研发是一种颇具吸引力的方法,可用于同时预防弱势群体中的多种传染病。犬瘟热病毒(CDV)和狂犬病病毒(RABV)都会在野生和家养食肉动物中引发致命疾病。虽然狂犬病疫苗是灭活疫苗,但减毒活犬瘟热疫苗对高度易感的野生动物仍保留残余毒力。在本研究中,我们基于重组疫苗株狂犬病病毒颗粒开发了重组二价候选疫苗,这些颗粒同时展示保护性犬瘟热病毒和狂犬病病毒糖蛋白抗原。重组病毒复制至接近野生型滴度,异源糖蛋白有效表达并整合到病毒颗粒中。用β-丙内酯灭活的重组病毒颗粒免疫雪貂可引发保护性狂犬病病毒抗体滴度,用表达犬瘟热病毒附着蛋白和融合蛋白的重组病毒组合免疫的动物可免受致命犬瘟热病毒攻击。然而,仅用表达犬瘟热病毒疫苗株 Onderstepoort 附着蛋白的狂犬病病毒免疫的动物死于较新的野生型毒株感染,这表明对更保守的融合蛋白的免疫反应有助于抵抗异源犬瘟热病毒株。狂犬病病毒和犬瘟热病毒(CDV)在许多食肉动物中导致高死亡率和死亡。虽然狂犬病疫苗是灭活的,因此具有出色的安全性和高稳定性,但减毒活犬瘟热疫苗在高度易感物种中可保留残余毒力。在此我们生成了表面携带一种犬瘟热病毒糖蛋白的重组灭活狂犬病病毒。用携带犬瘟热病毒融合和附着糖蛋白的重组狂犬病病毒混合物对雪貂进行两次免疫可使其免受致命犬瘟热病毒攻击,而按照相同免疫方案仅接受携带犬瘟热病毒附着蛋白的重组狂犬病病毒的所有动物均死亡。无论使用何种犬瘟热病毒抗原,所有动物均产生了针对狂犬病病毒的保护性滴度,这说明基于狂犬病病毒的二价疫苗可诱导针对两种病原体的保护性免疫反应。
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