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

Background/Objectives: The dengue virus remains endemic in over 100 countries, transmitted by mosquito bites. Current management relies on supportive care, as no highly effective vaccine or approved antiviral exists. The CYD-TDV (Dengvaxia^®) vaccine, licensed since 2015 with around 60% efficacy, raises the risk of severe dengue in seronegative children. The newer "Qdenga" vaccine offers up to 80% efficacy after a year but provides suboptimal protection against DENV-3 in seronegative individuals. Over the past two decades, virus-like particles (VLPs) have gained attention as safe, replication-incompetent vaccine platforms. This study evaluates the toxicity profile of dengue VLP-based antigens in BALB/c mice. Methods: A total of 80 BALB/C mice were randomly divided into two experimental groups: acute and chronic. Each group consisted of a treatment subgroup (10 males and 10 females) and a control subgroup (10 males and 10 females). In the acute group, the VLP was administered intramuscularly on day 1, while in the chronic group, a second VLP dose was given on day 14. The study was conducted over a 28-day period. Throughout the experiment, body temperature, body weight, mortality, and clinical signs were monitored regularly to assess the functional condition of various organs. Results: The results showed no notable alterations in mortality rates, body temperature, body weight, clinical signs, or histopathological observations of the examined organs across all groups, including in the hematological and blood biochemical parameters. Conclusions: The administration of tetravalent dengue VLP vaccine in BALB/c mice did not result in adverse effects in acute or chronic toxicity evaluations. Therefore, the VLP supports progression toward clinical evaluation, with dendritic cell activation providing additional rationale.