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

Day-Yu Chao, Wen-Fan Shen, Jedhan Ucat Galula, Jiun-Hung Liu, Mei-Ying Liao, Chang-Hao Huang, Yu-Chun Wang, Han-Chung Wu, Jian-Jong Liang, Yi-Ling Lin, Matthew T. Whitney, Gwong-Jen J. Chang, Sheng-Ren Chen , Shang-Rung Wu

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Received: 25th February 18

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.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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