Targeting Dendritic Cells with Virus-like Particles: Toward Safer and More Immunogenic Vaccines

Area of Science:

• Virology
• Immunology
• Toxicology

Background:

• Dengue virus is a major global health threat, endemic in over 100 countries, with current management limited to supportive care.
• Existing dengue vaccines like CYD-TDV and Qdenga have limitations, including safety concerns in seronegative individuals and variable efficacy.
• Virus-like particles (VLPs) are emerging as safe, replication-incompetent platforms for vaccine development.

Purpose of the Study:

• To evaluate the toxicity profile of dengue VLP-based antigens in a preclinical mouse model.
• To assess the safety of a tetravalent dengue VLP vaccine in both acute and chronic exposure scenarios.

Main Methods:

• Eighty BALB/c mice were divided into acute and chronic groups, each with treatment and control subgroups.
• Mice received intramuscular VLP administration on day 1 (acute) or days 1 and 14 (chronic) over a 28-day period.
• Monitoring included body temperature, weight, mortality, clinical signs, and histopathological examination of organs, alongside hematological and biochemical analyses.

Main Results:

• No significant differences were observed in mortality rates, body temperature, or body weight between VLP-treated and control groups.
• No adverse clinical signs or pathological changes were noted in the histopathological examination of organs.
• Hematological and blood biochemical parameters remained within normal ranges, indicating no toxicity.

Conclusions:

• The tetravalent dengue VLP vaccine demonstrated a favorable safety profile in BALB/c mice during acute and chronic toxicity assessments.
• The VLP vaccine did not induce adverse effects, supporting its progression toward human clinical trials.
• Dendritic cell activation by the VLP platform provides an additional rationale for its further development as a dengue vaccine.