DENV-3 precursor membrane (prM) glycoprotein enhances E protein immunogenicity and confers protection against DENV-2 infections in a murine model

• Published in: Human vaccines & immunotherapeutics Vol. 17; no. 5; pp. 1271 - 1277
• Main Authors: Dias, Roberto S., Teixeira, Michelle D., Xisto, Mariana F., Prates, John W. O., Silva, Jessica D. Da, Mello, Iago O., Silva, Cynthia C. Da, De Paula, Sérgio O.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 04.05.2021; Taylor & Francis Group
• Subjects: Dengue; DNA vaccines; e protein; prM protein; Research Paper; e protein; DNA vaccines; prM protein; Dengue
• ISSN: 2164-5515; 2164-554X
• DOI: 10.1080/21645515.2020.1826798

To improve a DNA vaccine containing the truncated dengue virus serotype 2 (DENV-2) envelope (E) protein and evaluate the influence of precursor membrane (prM) glycoprotein polymorphism on E protein immunogenicity, two vaccine candidates have been constructed by upstream insertion of the DENV-2 and DENV-3 prM genes into the DENV-2 E gene, named pCID2EtD2prM and pCID2EtD3prM, respectively. Both constructs were able to induce antibody production, which were neutralizing against DENV-2 in a murine model. Splenocytes of immunized groups, when challenged with virus, demonstrated Th1 cytokine pattern and proliferation, in addition to the increase of specific T cells. Vaccine candidates pCID2EtD2prM and pCID2EtD3prM confer 70% and 90% protection against DENV-2, respectively. The pCID2EtD3prM plasmid conferred only 40% protection in the lethal challenge with DENV-2. The results demonstrate that DENV-3 prM has a greater influence on the immunogenicity of the E protein and, probably due to its role as a chaperone, these results may be related to the correct folding and, consequently, an increase in the presentation efficiency of produced transcripts.