Dengue Infection Alters Immune System and Influences Vaccine Effectiveness

Recent research highlights how dengue virus infections can cause long-lasting changes in the immune system, affecting how individuals respond to subsequent vaccines and infections. Similar to a computer operating system update, dengue infection can reprogram immune cells, leaving a genetic imprint that persists over time and influences immune responses.

A study published in the journal Med by scientists from Duke-NUS Medical School, in collaboration with international researchers, examined these immune alterations through clinical trials involving volunteers from the US and Singapore. Participants with prior dengue infection exhibited distinct gene activity patterns in their immune cells even before vaccination, indicating that natural infection leaves a lasting genetic marker—something not observed in vaccinated individuals without previous infection.

Dr. Eugenia Ong explained that natural dengue infection induces a reset in the immune system, creating a new baseline that might explain the increased severity of secondary infections. The first dose of dengue vaccine in previously infected individuals was found to provoke a stronger immune response compared to those without prior exposure, who generally exhibit weaker responses even after two doses.

This phenomenon, termed trained immunity, has also been observed in other diseases like malaria and aftermath of certain vaccines like BCG. Professors from Duke-NUS emphasized that effective immune training requires a substantial activation—akin to a full game—rather than a light warm-up from vaccination alone. Key genes involved in initial antiviral responses were less active in previously infected individuals, potentially explaining why secondary infections can sometimes be more severe.

Understanding these immune reprogramming mechanisms provides crucial insights into improving dengue vaccines and shaping health policies. While developing a perfect dengue vaccine may remain elusive in the next decade, current vaccines—despite their imperfections—are vital in reducing the global burden of over 100 million cases annually.

This research opens new avenues for exploring how long-term immune alterations affect responses to other infections and vaccines, ultimately guiding future vaccine development and public health strategies.