Cristina Possas ^1* Ernesto T. Marques ^2,3* Alessandra Oliveira ⁴ Suzanne Schumacher ⁴ Adelaide Antunes ^4,5 Akira Homma ⁶

• ¹ Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
• ² Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Pernambuco, Brazil
• ³ Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
• ⁴ School of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Paraná, Brazil
• ⁵ National Institute of Industrial Property, Rio de Janeiro, Brazil
• ⁶ Bio-Manguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, Paraná, Brazil

Introduction: There has been a dramatic global surge in Dengue Fever (DF) in recent years, with projected 100-400 million cases annually and large outbreaks expected every 3-4 years. This concerning scenario is in sharp contrast to the very low availability of Dengue vaccines to meet this spiraling demand, affecting particularly developing countries in Latin American and Africa. In our study we aim to identify current vaccine development constraints, from a technological perspective, based on clinical trials and patent landscape data. Methods: This study was conducted in a two-step methodology: first, candidates and launched products and methods used in development or as part of Dengue Fever (DF) vaccines have been identified from the Cortellis Drug Discovery Intelligence (CDDI) platform. Second, the Derwent Innovation database was used to retrieve patent documents related to Dengue vaccines. Data collected in the period 2014-2024 (to identify the candidate and or launched vaccines) and 2018-2022 (to identify patent documents) with claims involving applications to Dengue vaccine development. We presented these descriptive data in the following format: quantitative and qualitative assessment describing the vaccine development scenario and the claimed vaccine technologies. Results: Our study indicated that 65% of Dengue vaccines are still in Phase 1 of development. The few current dengue vaccines that have reached phase 3 (1) and launched (2) have shown limited levels of individual protection for one or more dengue serotypes and an anemic pipeline of the next generation of more effective tetravalent dengue vaccines. Although the intelligent use of multiple dengue vaccine formulations in immunizations campaigns can result in an effective protection against all serotypes at population level, its implementation is complex and challenging. The results of our study evidence thus a worrisome global situation regarding the development of new Dengue vaccine candidates. Conclusion: To reverse this scenario, there is an urgent need of to implement new knowledge governance approaches and business models to stimulate an exponential increase in global vaccine development funding for dengue and several other vaccines.