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Biodistribution and immunity of adenovirus 5/35 and modified vaccinia Ankara vector vaccines against human immunodeficiency virus 1 clade C.
Shimada, Masaru; Wang, Haibin; Ichino, Motohide; Ura, Takehiro; Mizuki, Nobuhisa; Okuda, Kenji.
Afiliación
  • Shimada M; Department of Molecular Biodefense Research, Yokohama City University, Yokohama, 2360004, Japan. mshimada@yokohama-cu.ac.jp.
  • Wang H; BioRay Pharmaceutical Co., Ltd., Taizhou, Zhejiang, 318000, China.
  • Ichino M; Department of Immunology, Yokohama City University, Yokohama, 2360004, Japan.
  • Ura T; Department of Ophthalmology and Visual Science, Yokohama City University, Yokohama, 2360004, Japan.
  • Mizuki N; Department of Ophthalmology and Visual Science, Yokohama City University, Yokohama, 2360004, Japan.
  • Okuda K; Department of Molecular Biodefense Research, Yokohama City University, Yokohama, 2360004, Japan.
Gene Ther ; 29(10-11): 636-642, 2022 11.
Article en En | MEDLINE | ID: mdl-34987192
Previously, we developed a chimeric adenovirus type 5 with type 35 fiber (Ad5/35), which has high tropism to dendritic cells and low hepatoxicity. For further clinical use, we constructed two recombinant vectors expressing human immunodeficiency virus 1 (HIV-1) clade C gag (Ad5/35-Cgag and MVA-Cgag). The biodistribution of the two viral vectors in a mouse model and immunity in monkeys were assessed. The mice received a single intramuscular injection with the vectors alone. The gag gene in the tissues were periodically detected using a real-time quantitative polymerase chain reaction. The distribution of Ad5/35 was also detected using an in vivo imaging system, followed by luciferase-expressing Ad5/35 administration. We found that Ad5/35-Cgag DNA and luciferase activity were detectable until 8 weeks post-administration, whereas MVA-Cgag was undetectable 72 h post-administration. Furthermore, viral administration did not increase serum aspartate aminotransferase and alanine aminotransferase levels in either mouse or monkey models. Moreover, intramuscular administration of Ad5/35-Cgag induced the gag-specific antibody level and IFNγ-secreting PBMCs, the boost with MVA-Cgag further increased the responses and lasted more than 20 weeks from the initial administration. These data demonstrate that Ad5/35 and MVA vectors are safe for in vivo use, and prime-boost with Ad5/35-MVA vaccines is suitable for clinical use against HIV-1 clade C.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vaccinia / VIH-1 / Vacunas contra el SIDA / Infecciones por Adenoviridae / Vacunas de ADN Límite: Animals / Humans Idioma: En Revista: Gene Ther Asunto de la revista: GENETICA MEDICA / TERAPEUTICA Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vaccinia / VIH-1 / Vacunas contra el SIDA / Infecciones por Adenoviridae / Vacunas de ADN Límite: Animals / Humans Idioma: En Revista: Gene Ther Asunto de la revista: GENETICA MEDICA / TERAPEUTICA Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido