Dengue virus infection reprograms baseline innate immune gene expression

Area of Science:

• Immunology
• Vaccinology
• Genomics

Background:

• Dengue vaccines show varied efficacy based on prior dengue virus (DENV) exposure.
• The tetravalent dengue vaccine TAK-003 demonstrates lower immunogenicity in seronegative individuals compared to seropositive individuals.
• Understanding baseline immune differences is crucial for optimizing dengue vaccination strategies.

Purpose of the Study:

• To investigate the host response to the TAK-003 dengue vaccine.
• To identify differences in gene expression between dengue-seropositive and dengue-seronegative individuals.
• To explore the impact of prior DENV infection on immune responses to vaccination.

Main Methods:

• Whole-genome microarray analysis of host response to TAK-003.
• Bulk whole-blood RNA sequencing to assess baseline gene expression.
• Comparison of gene expression profiles in three independent cohorts.

Main Results:

• Host response to TAK-003 in seropositive individuals is partly driven by innate immune reprogramming from prior DENV infection.
• Significant differential immune gene expression exists between seropositive and seronegative individuals at baseline.
• Prior DENV infection reprogrammed innate immune markers, affecting cell cycle and innate immunity gene modules, but vaccination did not induce similar reprogramming.

Conclusions:

• Dengue virus infection leaves a lasting imprint on the innate immune system.
• This immune system alteration may influence dengue vaccine outcomes.
• Findings suggest a potential link between prior DENV infection, innate immunity, and secondary dengue pathogenesis.