Marielena Vogel Saivish, The University of Texas Medical Branch
Dengue, a mosquito-borne disease, affects millions of people every year across Asia, Africa and Latin America. And it’s expanding geographically as warmer temperatures and urban growth allow mosquito populations to thrive in new regions.
At first glance, dengue seems like an obvious candidate for vaccination. It is caused by a virus. Infection triggers an immune response. Vaccines against similar viruses already exist.
But dengue is complicated. It is not caused by just one virus, but by four closely related ones known as serotypes. When someone is infected with one, the immune system usually protects them against that specific type – but not against the other three. In some cases, a previous infection can actually make a new infection happen more easily.
Little wonder that dengue is one of the most common mosquito-borne viral diseases in the world. Scientists estimate that around 390 million infections occur every year, and it’s an important public health concern in Africa.
Currently, one dengue vaccine is established in global clinical use. Dengvaxia is only for use if a person has been infected before. A newer vaccine – TAK-003 – has been recommended by the World Health Organization for use in children aged 6–16 years in settings with high dengue transmission, regardless of prior infection status. It is administered in two doses. Additionally, next-generation vaccines are being developed, including one in Brazil.
Our work as researchers studying viral immunology and mosquito-borne diseases focuses on understanding how immune responses shape protection against viruses such as dengue.
Our recent research reviewed decades of dengue vaccine studies, including clinical trials and immunological analyses. The evidence shows that dengue vaccines must generate a carefully balanced immune response against all four viral serotypes. If protection is incomplete or uneven, it may increase the risk of severe disease in some individuals.
Understanding these immune mechanisms is essential for designing safer and more effective vaccines.
Overall, vaccine performance still varies depending on factors such as prior infection, age and transmission intensity, meaning that vaccination strategies must be carefully tailored to each population.
Dengue outbreaks and evidence of transmission have been documented in Kenya, Tanzania, Sudan, Senegal and Côte d’Ivoire. It may be even more widespread on the continent than previously recognised, partly because testing and surveillance systems are still developing in many regions.
The disease spreads through the bite of infected Aedes mosquitoes, particularly Aedes aegypti. These mosquitoes breed in standing water, which is often near where people live. Dengue symptoms include high fever, headache, pain behind the eyes, muscle and joint pain, nausea and rash. Most people recover within about a week, but in some cases the infection can become severe and lead to bleeding, organ damage or shock. Transmission tends to increase during rainy seasons, when mosquito populations expand.
In recent decades, cases have risen sharply as urbanisation, travel and climate change have expanded mosquito habitats.
Infection with one dengue serotype usually provides long-term protection against that specific version. The problem arises when a person later becomes infected with a different serotype.
Instead of offering protection, antibodies from the first infection can sometimes help the second virus enter cells more easily.
This process, known as antibody-dependent enhancement, has been linked to more severe disease, including dengue hemorrhagic fever and shock. In simple terms: the immune system’s memory can sometimes backfire. That biological feature has made vaccine development uniquely difficult.
Our research revealed several important patterns.
First, vaccine performance depends heavily on whether someone has previously had dengue. In some large trials, vaccines provided good protection for people who had been infected before. But for individuals who had never encountered the virus, protection was weaker and in some cases, the risk of hospitalisation increased after later infection.
Second, the quality of antibodies matters as much as the quantity. It is not enough to produce high levels of antibodies. Those antibodies must be strongly neutralising, meaning they can fully block the virus. Weakly neutralising antibodies may fail to stop infection and could contribute to enhanced disease.
Third, age and transmission intensity influence outcomes. In areas where dengue circulates widely and many people are exposed early in life, vaccine performance patterns differ from regions where first exposure occurs later.
Countries that previously had limited dengue activity are now facing outbreaks. Vaccines remain one of the most powerful public health tools.
But incomplete understanding can erode public trust. Confusion around dengue vaccination in the past contributed to fear and misinformation in some communities.
For example, the introduction of the Dengvaxia vaccine generated controversy in the Philippines after follow-up studies showed that vaccine outcomes differed depending on whether people had previously been infected with dengue. Clear explanation of what happened and why is essential.
Evidence from multiple clinical trials, epidemiological studies and immunological research groups worldwide shows that dengue vaccines must be evaluated not only for overall effectiveness but also for how they perform in different populations. These include people with and without prior infection, different age groups, and regions with varying levels of transmission.
Our research also demonstrates that immune responses must be carefully measured. Protection is not simply about generating antibodies. It is about generating the right kind.
These insights are already shaping newer vaccine strategies. Some candidates focus on improving balanced immunity across all four serotypes. Others aim to refine how immune responses are stimulated to reduce the possibility of enhancement.
Several lessons emerge for countries preparing for dengue outbreaks.
First, vaccination strategies must be tailored to epidemiological context. In regions where most adolescents or adults have already been infected, certain vaccines may offer substantial benefit. In lower-transmission settings, pre-vaccination screening to determine prior exposure may be necessary.
Second, long-term safety monitoring is critical. Dengue vaccine effects may only become fully visible years after rollout, once vaccinated individuals experience natural infection. Surveillance systems must be strong enough to detect patterns early.
Third, communication must be transparent. Public confidence depends on clear explanations of both benefits and risks. Complex science does not need to be simplified into misleading certainty. It can be explained honestly and clearly.
Finally, research investment must continue. Dengue illustrates that not all viruses follow simple rules.
The broader lesson extends beyond dengue. As mosquito-borne diseases spread due to environmental change, other complex viruses may pose similar challenges. Learning how to design vaccines for biologically intricate pathogens is increasingly important.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
(The Conversation/HG)