A tetravalent dengue virus-like particle vaccine induces high levels of neutralizing antibodies and reduces dengue replication in non-human primates.

Dengue virus (DENV) represents a significant global health burden, with 50% of the world's population at risk of infection, and there is an urgent need for next-generation vaccines. Virus-like particle (VLP)-based vaccines, which mimic the antigenic structure of the virus but lack the viral genome, are an attractive approach. Here, we describe a dengue VLP (DENVLP) vaccine which generates a neutralizing antibody response against all four DENV serotypes in 100% of immunized non-human primates for up to 1 year. Additionally, DENVLP vaccination produced no ADE response against any of four DENV serotypes in vitro. DENVLP vaccination reduces viral replication in a non-human primate challenge model. We also show that transfer of purified IgG from immunized monkeys into immunodeficient mice protects against subsequent lethal DENV challenge, indicating a humoral mechanism of protection. These results indicate that this DENVLP vaccine is immunogenic and can be considered for clinical evaluation. Immunization of non-human primates with a tetravalent DENVLP vaccine induces high levels of neutralizing antibodies and reduces the severity of infection for all four dengue serotypes.IMPORTANCEDengue is a viral disease that infects nearly 400 million people worldwide and causes dengue hemorrhagic fever, which is responsible for 10,000 deaths each year. Currently, there is no therapeutic drug licensed to treat dengue infection, which makes the development of an effective vaccine essential. Virus-like particles (VLPs) are a safe and highly immunogenic platform that can be used in young children, immunocompromised individuals, as well as healthy adults. In this study, we describe the development of a dengue VLP vaccine and demonstrate that it induces a robust immune response against the dengue virus for over 1 year in monkeys. The immunity induced by this vaccine reduced live dengue infection in both murine and non-human primate models. These results indicate that our dengue VLP vaccine is a promising vaccine candidate.

Relationship Between Submental Superficial Layer Hardness and Tongue Pressure Determined Using a Tissue Durometer.

Aging affects the tongue and suprahyoid muscles, causing dysphagia and undernutrition. We hypothesized that tongue function would affect submental superficial layer hardness. Tongue movements during water retention between the tongue and palate are the same as those required during bolus formation, involving internal and external tongue muscle movement. In 28 healthy adults (14 males, 14 females, average age 28.7 ± 2.9 years), we measured the submental superficial layer characteristics (frequency [tension], stiffness, decrement [inverse of resilience], relaxation, and creep [deformation over time]) using a simple tissue durometer (MyotonPRO®), and examined their relationship with maximum voluntary tongue pressure. The tissue durometer sensor was placed in the submental region, where there is no intervening bone. Measurements were performed at rest and while retaining 5 mL water. Tongue pressure was measured using a tongue pressure-measuring device. The submental superficial layer hardness differed significantly between rest and during water retention. During water retention, frequency and stiffness were high, while decrement, relaxation, and creep were low. When pressure is applied to the palate, such as during water retention the inner tongue muscle, which changes the tongue's shape, and the outer tongue muscle, which moves the tongue laterally, are active. However, the change in the hardness of the submental superficial layer during water retention may be related to the suprahyoid muscles that are present in this layer. The results of this study suggested that the hardness of the submental superficial layer changed during water retention, and that tongue movement could be measured from outside the mouth.