A dengue monovalent vaccine with novel structure provides cross-protection against four serotypes of dengue virus

Chao, D.-Y.; Shen, W.-F.; Galula, J. U.; Liu, J.-H.; Liao, M.- Y.; Huang, C.-H.; Wang, Y.-C.; Wu, H.-C.; Liang, J.-J.; Lin, Y.- L.; Whitney, M. T.; Chang, G.-J. J.; Chen, S.-R.; Wu, S.-R.

doi:10.1101/275685

bioRxiv · 10.1101/275685

A dengue monovalent vaccine with novel structure provides cross-protection against four serotypes of dengue virus

Chao, D.-Y.·Shen, W.-F.·Galula, J. U.·Liu, J.-H.·Liao, M.- Y.·Huang, C.-H.·Wang, Y.-C.·Wu, H.-C.·Liang, J.-J.·Lin, Y.- L.·Whitney, M. T.·Chang, G.-J. J.·Chen, S.-R.·Wu, S.-R.

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Abstract

Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. The vaccine candidates under development require a tetravalent immunogen to induce a balanced immunity against all four serotypes of dengue virus. Herein we show that mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher and broader neutralization antibodies (NtAbs) against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. The cryo-electron microscopy reconstruction showed that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes. Most importantly, maternally transferred antibodies derived from mD2VLP-vaccinated female mice protected suckling mice from lethal challenge by all four serotypes of DENV. Our results support the fact that a universal dengue vaccine that protects against all four serotypes of dengue viruses can be achieved by using an immunogen such as mD2VLP.

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Chao, D.-Y., Shen, W.-F., Galula, J. U., Liu, J.-H., Liao, M.- Y., Huang, C.-H., Wang, Y.-C., Wu, H.-C., Liang, J.-J., Lin, Y.- L., Whitney, M. T., Chang, G.-J. J., Chen, S.-R., Wu, S.-R.. 2018-03-05. A dengue monovalent vaccine with novel structure provides cross-protection against four serotypes of dengue virus. https://doi.org/10.1101/275685

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