Identification of multifunctional T-cell peptide epitopes for the development of DNA vaccines against dengue virus

Dengue virus (DENV) is an important arthropod-borne virus that poses a global health threat, with half of the world’s population at risk of infection. Currently, there is a lack of safe and effective vaccines for its prevention. Antibody-dependent enhancement (ADE) occurs when cross-reactive antibodies fail to neutralize heterologous DENV serotypes effectively, facilitating viral entry into Fc receptor-bearing cells and leading to more severe disease. It is reported that multifunctional T cells are closely related to the protective effects of the vaccine. We selected 25 peptide candidates based on predictions from the IEDB database and relevant literature. These peptides were validated to stimulate the production of multifunctional T cells. The DNA sequences of the corresponding peptides were cloned into the pVAX1 vector, and monovalent DNA vaccines for DENV 1–4 were constructed. <i>We analyzed cellular immunity, symptom scores, body weight changes, and survival rates after DENV challenge with the identical immunizing strain</i>.Our studies confirmed that DNA vaccines can protect mice against DENV challenge. Compared with control groups, mice immunized with our DNA vaccines demonstrated better immune protection after being challenged with the corresponding strain of DENV. Our studies provide a basis for the development of new DENV tetravalent vaccines. In this study, we developed novel DNA vaccines targeting dengue fever, a disease caused by four distinct serotypes of the dengue virus (DENV1–4). Our vaccines are designed to include key T-cell epitopes from each serotype, enhancing the immune system’s ability to recognize and respond effectively. The results from our experiments showed that our vaccines induce strong multifunctional T-cell responses in test animals, providing robust immunity against all four serotypes. Furthermore, the vaccines demonstrated safety and efficacy in animal trials, paving the way for future human trials. This innovative approach promises comprehensive and lasting immunity against dengue, addressing the limitations of current vaccines and significantly impacting global health efforts. Our work underscores the importance of developing broad-spectrum vaccines to tackle diseases with multiple serotypes, making it relevant for both scientists and non-scientists alike.