Comparison of Neutralizing Dengue Virus B Cell Epitopes and Protective T Cell Epitopes With Those in Three Main Dengue Virus Vaccines

Abstract

The four serotypes of Dengue virus (DENV1-4) are arboviruses (arthropod-borne viruses) that belong to the Flavivirus genus, Flaviviridae family. They are the causative agents of an infectious disease called dengue, an important global public health problem with significant social-economic impact. Thus, the development of safe and effective dengue vaccines is a priority according to the World Health Organization. Only one anti-dengue vaccine has already been licensed in endemic countries and two formulations are under phase III clinical trials. In this study, we aimed to compare the main anti-dengue virus vaccines, DENGVAXIA®, LAV-TDV, and TAK-003, regarding their antigens and potential to protect. We studied the conservation of both, B and T cell epitopes involved in immunological control of DENV infection along with vaccine viruses and viral isolates. In addition, we assessed the population coverage of epitope sets contained in each vaccine formulation with regard to different human populations. As main results, we found that all three vaccines contain the main B cell epitopes involved in viral neutralization. Similarly, LAV-TDV and TAK-003 contain most of T cell epitopes involved in immunological protection, a finding not observed in DENGVAXIA®, which explains main limitations of the only licensed dengue vaccine. In summary, the levels of presence and absence of epitopes that are target for protective immune response in the three main anti-dengue virus vaccines are shown in this study. Our results suggest that investing in vaccines that contain the majority of epitopes involved in protective immunity (cellular and humoral arms) is an important issue to be considered.

A Novel Orf Virus D1701-VrV-Based Dengue Virus (DENV) Vaccine Candidate Expressing HLA-Specific T Cell Epitopes: A Proof-of-Concept Study

“…Thus, despite the recent development of several promising candidates, there remains a need for additional vaccines and strategies, most notably those that feature new concepts and that have the potential to elicit both humoral and cellular immune responses [ 28 , 29 , 30 ]. The increased risk for severe outcomes in DENV-naïve individuals who received the CYD-TDV vaccine demonstrated that the specific immune mechanisms involved in vaccine-associated disease enhancement are not yet well-understood [ 29 , 31 , 32 , 33 ]. Several studies have suggested that specific T cell responses may provide control of DENV infections and thus may be essential components of an efficient immune response [ 30 , 34 , 35 , 36 ].…”

Neutralizing antibody response after immunization with a COVID‐19 bivalent vaccine: Insights to the future

“…As previously described, 16,17 the IEDB conservation analysis tool (http://tools.iedb.org/conservancy) was used to determine epitope conservation among the SARS-CoV-2 S protein sequences contained in our data sets. In the present study, only fully conserved B cell epitopes which are target for NAbs were considered (100% conserved in the S protein amino acid sequences of the datasets used).…”

“…13 Additionally, we conducted immunoinformatic analysis to highlight unique and shared conserved NAb epitopes between SARS-CoV-2 variants (WT, BA.1, BA.4, BA.5, and BQ.1.1), as previously described. 16,17 All the research complied with all relevant ethical and biosafety guidelines. Ethical approval was obtained from the Institutional Ethics Committee of the Federal University of Western Bahia (CAAE 40779420.6.0000.8060).…”

Is new dengue vaccine efficacy data a relief or cause for concern?

“…Most humoral immunity epitopes are located within the domains of the DENV envelop (E) protein while cellular immunity epitopes are located on the non-structural (NS) proteins 27 , 70 . As noted in Fig.…”