Wednesday, June 07, 2023
Emergex Vaccines Holding Limited, a clinical-stage biotechnology company, has reported positive outcomes from its initial clinical trial of DengueTcP, a candidate aimed at combatting the Dengue virus and Dengue Fever.
The primary goal of the trial, called naNO-DENGUE, was to evaluate the safety, tolerability, and reactogenicity of two different doses of DengueTcP administered via intradermal microneedle injection to healthy volunteers. Both dosage levels of DengueTcP were found to be safe and well tolerated, with no serious adverse events reported. Most adverse events were mild and temporary. In terms of safety, both doses were considered suitable for further trials.
The assessment of immunogenicity yielded the following results:
Following immunization, there were statistically significant increases in virus-specific effector CD8+ T cells and memory CD8+ T cells.
Notably, the elevated T cells included CXCR3+ central memory and differentiated effector memory cells. These T cell subsets are particularly important as they play a role in locating virus-infected cells in the skin and providing protective immunity against Dengue infection.
DengueTcP did not induce the production of anti-DENV antibodies, which is a favorable outcome as it reduces the risk of antibody-dependent enhancement (ADE) of the disease, as observed in trials of traditional vaccines.
In summary, the preliminary results indicate that treatment with DengueTcP stimulates the generation of memory T cells in the bloodstream that have the ability to target infected tissues. These clinical findings demonstrate the potential of Emergex's therapeutic platform to successfully induce virus-specific CD8+ T cell responses. The data from this trial support the further development of Emergex's platform, which has the potential to provide cross-reactive immunity against a range of existing or emerging viral and intracellular pathogens.
The naNO-DENGUE Trial, registered under ClinicalTrials.gov with the identifier NCT04935801, was a Phase I clinical study conducted on healthy adults to investigate the safety and efficacy of DengueTcP, a synthetic nanoparticle-based immune set-point, against the Dengue virus. The trial was carried out at the Centre for Primary Care and Public Health in Lausanne, Switzerland, and involved the enrollment of 26 individuals aged 18-45 years. It followed a randomized, double-blind, vehicle-controlled design, where participants were randomly assigned to receive either DengueTcP or a comparator (nanocluster without peptide antigens, vehicle-nanocluster). A six-month follow-up period was implemented to monitor the participants after the initial injection.
DengueTcP, developed by Emergex, is specifically designed to stimulate a targeted CD8+ T cell immune response against the Dengue virus while preserving the humoral response. It comprises synthetic peptide antigens from the four serotypes of the Dengue virus, which are presented on ultrasmall carbohydrate-passivated nanoclusters.
Immunotope Inc. employed an immunoproteomics approach to identify the peptide antigens presented by major histocompatibility complex Class I (MHC-I) molecules on the surface of Dengue-infected cells, as they represent the actual targets of the CD8+ T cell response during natural infection. Nine peptide antigens were selected from this expression library for inclusion in the DengueTcP product, based on their ability to induce a cross-reactive immune response against all four Dengue virus serotypes and other Flaviviruses.
To ensure the stability and targeted delivery of the peptide antigens, they are attached to the nanocluster core using specific carbohydrates. This self-assembling nanocluster-based delivery system offers protection against proteolytic degradation, facilitates the delivery to antigen presenting cells, and promotes the induction of the desired cellular immune response. The use of nanoclusters allows for effective immune response activation with low doses of peptide antigens. For administration, DengueTcP is delivered through intradermal injection using a microneedle, with the possibility of a dermal patch in the future, to ensure standardization and mimic the natural recruitment of immune cells during mosquito-borne infections.
Preclinical studies using human peripheral blood mononuclear cells and animal models have demonstrated the safety of DengueTcP and nanoclusters. The naNO-DENGUE Trial aimed to evaluate the safety of this T cell-priming immune set-point candidate, specifically designed to induce a CD8+ T cell immune response for the prevention of acute and severe manifestations of viral infections caused by Dengue and other Flaviviruses. Emergex is actively collaborating with governments worldwide to make DengueTcP accessible to high-risk populations, offering a promising option in the battle against Dengue.
