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Nanoparticle-detained toxins for safe and effective vaccination

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Abstract

Toxoid vaccines—vaccines based on inactivated bacterial toxins—are routinely used to promote antitoxin immunity for the treatment and prevention of bacterial infections1,2,3,4. Following chemical or heat denaturation, inactivated toxins can be administered to mount toxin-specific immune responses. However, retaining faithful antigenic presentation while removing toxin virulence remains a major challenge and presents a trade-off between efficacy and safety in toxoid development. Here, we show a nanoparticle-based toxin-detainment strategy that safely delivers non-disrupted pore-forming toxins for immune processing. Using erythrocyte membrane-coated nanoparticles and staphylococcal α-haemolysin, we demonstrate effective virulence neutralization via spontaneous particle entrapment. Compared with vaccination with heat-denatured toxin, mice vaccinated with the nanoparticle-detained toxin showed superior protective immunity against toxin-mediated adverse effects. We find that the non-disruptive detoxification approach benefited the immunogenicity and efficacy of toxoid vaccines. We anticipate that this study will open new possibilities in the preparation of antitoxin vaccines against the many virulence factors that threaten public health.

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Figure 1: Schematic and in vitro characterizations.
Figure 2: Nanotoxoid(Hla) neutralizes Hla virulence.
Figure 3: Nanotoxoid(Hla) vaccinations elicit strong Hla-specific antibody responses.
Figure 4: Nanotoxoid(Hla) vaccinations bestow strong protective immunity.

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Acknowledgements

This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (award no. R01DK095168) and by the National Science Foundation (grant DMR-1216461). B.L. is supported by a National Institutes of Health training grant (R25CA153915) from the National Cancer Institute.

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Contributions

L.Z. conceived and designed the experiments with C-M.H., R.F. and B.L. Experiments were performed by C-M.H., R.F. and B.L. All authors analysed and discussed the data and wrote the manuscript.

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Correspondence to Liangfang Zhang.

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The authors declare no competing financial interests.

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Hu, CM., Fang, R., Luk, B. et al. Nanoparticle-detained toxins for safe and effective vaccination. Nature Nanotech 8, 933–938 (2013). https://doi.org/10.1038/nnano.2013.254

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