Dengue, caused by infection with one of the four serotypes that compose the dengue virus, is a mosquito-borne disease
from the genus Aedes and continues to be among the most widespread pressing global health issues throughout the
tropical and subtropical regions of the world. Furthermore, each of the four virus serotypes, DENV-1 through DENV-4,
causes millions of infections annually, complicating efforts toward an effective vaccine due to partial immunity, which
increases the risk of severe disease through antibody-dependent enhancement. Vaccination solves the problem in the
most promising long-term-implication methods of reducing transmission rates and disease severity, but many challenges
inevitably await. This review examines advanced approaches and strategies in dengue vaccination with a focus on
overcoming key barriers, including ADEs, serotype diversity, and population considerations. Current vaccines, such as
Dengvaxia, have demonstrated efficacy but are limited by safety concerns, particularly in seronegative individuals. The
need for next-generation vaccines that provide broad, safe, and durable protection against all four serotypes is paramount.
Promising candidates include live attenuated vaccines such as TAK-003 and TV003/TV005, subunit vaccines targeting
specific viral proteins, and innovative platforms such as DNA and mRNA vaccines that offer rapid production and flexibility.
Advances in vaccine delivery, including nanoparticle-based systems and adjuvants, are improving immune responses and
stability, allowing vaccines to reach a wider population, especially in resource-limited areas. Effective immunization
strategies require the integration of dengue vaccines into global health programs, particularly in endemic areas such as
Latin America and Southeast Asia. Public-private partnerships and international cooperation will play a key role in scaling
up production, ensuring equal access and addressing logistical issues such as cold chain requirements. The future of
dengue vaccination depends on continued innovation in vaccine development, delivery and distribution. By overcoming
these challenges, it will be possible to significantly reduce the global burden of dengue and protect vulnerable populations
from this increasingly ubiquitous disease.

Keywords: Dengue fever; Vaccination; Antibody-dependent enhancement; Serotype diversity; Live-attenuated vaccines;
mRNA vaccines; Global immunization programs