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Immunization against Zika by entrapping live virus in a subcutaneous self-adjuvanting hydrogel

Nature Biomedical Engineering volume 7, pages 928–942 (2023)Cite this article

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Abstract

The threat of new viral outbreaks has heightened the need for ready-to-use vaccines that are safe and effective. Here we show that a subcutaneous vaccine consisting of live Zika virus electrostatically entrapped in a self-adjuvanting hydrogel recruited immune cells at the injection site and provided mice with effective protection against a lethal viral challenge. The hydrogel prevented the escape of the viral particles and upregulated pattern recognition receptors that activated innate antiviral immunity. The local inflammatory niche facilitated the engulfment of the virus by immune cells infiltrating the hydrogel, the processing and cross-presentation of antigens and the expansion of germinal centre B cells and induced robust antigen-specific adaptive responses and immune memory. Inflammatory immune niches entrapping live viruses may facilitate the rapid development of safe and efficacious vaccines.

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Fig. 1: Schematic of the virus-entrapping hydrogel (Vax).
Fig. 2: Characterization of Vax.
Fig. 3: Vax stimulates local innate immune responses.
Fig. 4: Cell recruitment.
Fig. 5: Local activation and antigen presentation.
Fig. 6: Systemic immune responses after vaccination with Ad5-prM-E-loaded Vax.
Fig. 7: Lymph node immune activation.
Fig. 8: ZIKV-loaded Vax ensured a protective immune response against ZIKV infection.

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Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. All data generated in this study, including source data for the figures, are available from figshare with the identifier https://doi.org/10.6084/m9.figshare.22126691.

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Acknowledgements

We thank J. Xuan for the assistance with CLSM data analysis, and Q. Huang and J. Chen for their help with histological analysis. This work was supported by The National Natural Science Foundation of China (22037005 and 21625105) and National Science & Technology Major Project (2016ZX10004001).

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Author notes

  1. These authors contributed equally: Haibin Hao, Shipo Wu.

Authors and Affiliations

  1. Department of Chemistry, Zhejiang University, Hangzhou, China

    Haibin Hao, Jiake Lin, Zitong Zheng, Yuemin Zhou, Ying Zhang, Fengchao Tian & Ruikang Tang

  2. Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou, China

    Haibin Hao, Jiake Lin, Zitong Zheng, Yuemin Zhou, Xurong Xu & Xiaoyu Wang

  3. Beijing Institute of Biotechnology, Beijing, China

    Shipo Wu, Qiang Guo, Mengsu Zhao, Yi Chen & Lihua Hou

  4. Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Xiaoyu Wang & Ruikang Tang

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Contributions

R.T. and X.W. initiated this study. X.W., R.T. and L.H. supervised and supported the research. H.H. performed most experiments including physicochemical characterization, cell experiments and animal experiments. Y.Z., F.T., X.W. and X.X. participated in performing the physicochemical characterization. J.L., Z.T., Y.M.Z., F.T., M.Z. and Y.C. participated in performing the animal experiments. H.H., X.W., Q.G. and S.W. analysed the data. The manuscript was written by H.H., X.W. and R.T. All authors provided critical feedback and helped shape the manuscript.

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Correspondence to Lihua Hou, Xiaoyu Wang or Ruikang Tang.

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Nature Biomedical Engineering thanks Michael Mitchell and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.

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Extended data

Extended Data Fig. 1 Vax hydrogel restricted systemic infection in vivo.

IFNAR1−/− mice were injected with PBS, ZIKV, and Vax; n = 5 for each group at days 5–28, and n = 3 for each group at day 52. a, Viral RNA in the spleens, kidneys, liver, hearts, brains and testes of PBS-injected mice was determined by real-time quantitative RT-PCR. L.O.D., limit of detection. b, The weight of testes from IFNAR1−/− mice after injected with PBS, ZIKV, or Vax. c, Representative H&E staining of the testes from IFNAR1−/− mice after injected with PBS, ZIKV, and Vax. d, Survival curves of IFNAR1−/− mice after injection with PBS, ZIKV or ZIKV loaded Vax; n = 6 for each group. All the mice in the Vax injected group survived compared with the 50% survival rate of the WT ZIKV group. Statistical analyses were performed by using log-rank test.

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Hao, H., Wu, S., Lin, J. et al. Immunization against Zika by entrapping live virus in a subcutaneous self-adjuvanting hydrogel. Nat. Biomed. Eng 7, 928–942 (2023). https://doi.org/10.1038/s41551-023-01014-4

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