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Biodistribution and immunity of adenovirus 5/35 and modified vaccinia Ankara vector vaccines against human immunodeficiency virus 1 clade C

Gene Therapy volume 29, pages 636–642 (2022)Cite this article

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Abstract

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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Fig. 1: Detection of Ad5/35-Cgag biodistribution using real-time PCR.
Fig. 2: Detection of MVA-Cgag biodistribution using real-time PCR.
Fig. 3: Bioluminescence in vivo imaging of Ad5/35-Luc in mice.
Fig. 4: Biochemical examination in virus-administered mice.
Fig. 5: HIV-specific immune responses in monkey.

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Acknowledgements

We thank Xian-Xing Xu and Yuan-Guo Cheng for their experimental assistance and Ms. Yuka Takeuchi for her secretary assistance. This work was partially supported by a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 20K09603). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.

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Author notes

  1. Kenji Okuda

    Present address: Okuda Vaccine Research Institute, Yokohama, 2350045, Japan

  2. Kenji Okuda

    Present address: Yokohama City University, Yokohama, 2360004, Japan

Authors and Affiliations

  1. Department of Molecular Biodefense Research, Yokohama City University, Yokohama, 2360004, Japan

    Masaru Shimada & Kenji Okuda

  2. BioRay Pharmaceutical Co., Ltd., Taizhou, Zhejiang, 318000, China

    Haibin Wang

  3. Department of Immunology, Yokohama City University, Yokohama, 2360004, Japan

    Motohide Ichino

  4. Department of Ophthalmology and Visual Science, Yokohama City University, Yokohama, 2360004, Japan

    Takehiro Ura & Nobuhisa Mizuki

Authors
  1. Masaru Shimada
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  3. Motohide Ichino
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Contributions

MS, HW, and TU contributed to perform experiments; MS and MI contributed to write the manuscript; MS, NM, and KO contributed to design experiments and discuss the manuscript.

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Correspondence to Masaru Shimada.

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Shimada, M., Wang, H., Ichino, M. et al. Biodistribution and immunity of adenovirus 5/35 and modified vaccinia Ankara vector vaccines against human immunodeficiency virus 1 clade C. Gene Ther 29, 636–642 (2022). https://doi.org/10.1038/s41434-021-00308-z

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