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Development of a new hydrogen peroxide–based vaccine platform

Abstract

Safe and effective vaccines are crucial for maintaining public health and reducing the global burden of infectious disease. Here we introduce a new vaccine platform that uses hydrogen peroxide (H2O2) to inactivate viruses for vaccine production. H2O2 rapidly inactivates both RNA and DNA viruses with minimal damage to antigenic structure or immunogenicity and is a highly effective method when compared with conventional vaccine inactivation approaches such as formaldehyde or β-propiolactone. Mice immunized with H2O2-inactivated lymphocytic choriomeningitis virus (LCMV) generated cytolytic, multifunctional virus-specific CD8+ T cells that conferred protection against chronic LCMV infection. Likewise, mice vaccinated with H2O2-inactivated vaccinia virus or H2O2-inactivated West Nile virus showed high virus-specific neutralizing antibody titers and were fully protected against lethal challenge. Together, these studies demonstrate that H2O2-based vaccines are highly immunogenic, provide protection against a range of viral pathogens in mice and represent a promising new approach to future vaccine development.

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Figure 1: H2O2 inactivates viruses without substantial damage to antigenic epitopes.
Figure 2: Vaccination with H2O2-LCMV induces multifunctional, cytolytic CD8+ T cells that protect against chronic virus infection.
Figure 3: Induction of protective orthopoxvirus-specific neutralizing antibody responses following H2O2-VV immunization.
Figure 4: Vaccination with H2O2-WNV induces strong neutralizing antibody responses and protects against lethal WNV infection.

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Acknowledgements

We thank E. Poore and M. Dubois for the growth of YFV and E. Hammarlund for the growth of monkeypox virus. This work was supported by US National Institutes of Health grants R56 AI076506 (to M.K.S.), UO1 AI082196 (to M.K.S.) and R43 AI079898 (to I.J.A. and M.K.S.) and Oregon National Primate Research Center grant 8P51 OD011092-53 (to M.K.S.).

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Authors and Affiliations

Authors

Contributions

M.K.S. conceived of the project. H.-P.R. performed the in vivo experiments, data analysis and figure preparation for the LCMV studies. I.J.A. performed the experiments, data analysis and figure preparation for the VV, YFV and WNV studies. I.J.A., H.-P.R. and M.K.S. wrote the manuscript, discussed the results and reviewed the manuscript before submission.

Corresponding author

Correspondence to Mark K Slifka.

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Competing interests

Oregon Health & Science University, M.K.S. and I.J.A. have a financial interest in Najít Technologies, a company that may have a commercial interest in the results of this research and technology. This potential individual and institutional conflict of interest has been reviewed and managed by Oregon Health & Science University and the Integrity Program Oversight Council.

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Amanna, I., Raué, HP. & Slifka, M. Development of a new hydrogen peroxide–based vaccine platform. Nat Med 18, 974–979 (2012). https://doi.org/10.1038/nm.2763

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