Vaccines (Aug 2024)

Preclinical Evaluation of Novel Sterically Optimized VLP-Based Vaccines against All Four DENV Serotypes

  • Dominik A. Rothen,
  • Sudip Kumar Dutta,
  • Pascal S. Krenger,
  • Anne-Cathrine S. Vogt,
  • Ilva Lieknina,
  • Jan M. Sobczak,
  • Albert D. M. E. Osterhaus,
  • Mona O. Mohsen,
  • Monique Vogel,
  • Byron Martina,
  • Kaspars Tars,
  • Martin F. Bachmann

DOI
https://doi.org/10.3390/vaccines12080874
Journal volume & issue
Vol. 12, no. 8
p. 874

Abstract

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Over the past few decades, dengue fever has emerged as a significant global health threat, affecting tropical and moderate climate regions. Current vaccines have practical limitations, there is a strong need for safer, more effective options. This study introduces novel vaccine candidates covering all four dengue virus (DENV) serotypes using virus-like particles (VLPs), a proven vaccine platform. The dengue virus envelope protein domain III (EDIII), the primary target of DENV-neutralizing antibodies, was either genetically fused or chemically coupled to bacteriophage-derived AP205-VLPs. To facilitate the incorporation of the large EDIII domain, AP205 monomers were dimerized, resulting in sterically optimized VLPs with 90 N- and C-termini. These vaccines induced high-affinity/avidity antibody titers in mice, and confirmed their protective potential by neutralizing different DENV serotypes in vitro. Administration of a tetravalent vaccine induced high neutralizing titers against all four serotypes without producing enhancing antibodies, at least not against DENV2. In conclusion, the vaccine candidates, especially when administered in a combined fashion, exhibit intriguing properties for potential use in the field, and exploring the possibility of conducting a preclinical challenge model to verify protection would be a logical next step.

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