Cytokine Profile of Children Hospitalized with Virologically-Confirmed Dengue during Two Phase III Vaccine Efficacy...

Area of Science:

• * Virology
• * Immunology
• * Vaccinology

Background:

• * Two large-scale efficacy studies of the recombinant yellow fever-17D-dengue virus, live-attenuated, tetravalent dengue vaccine (CYD-TDV) were conducted in Asia and Latin America.
• * The studies demonstrated significant protection against dengue disease during the initial two-year active surveillance phase.
• * Long-term follow-up for breakthrough dengue leading to hospitalization is ongoing.

Purpose of the Study:

• * To assess the cytokine profiles in acute sera of participants hospitalized with dengue.
• * To compare the cytokine profiles between CYD-TDV recipients and placebo recipients.
• * To investigate potential age-related differences in cytokine profiles for breakthrough dengue.

Main Methods:

• * Serum concentrations of 38 cytokines were measured using the Milliplex Human Cytokine MAGNETIC BEAD Premixed 38 Plex kit.
• * Partial least squares discriminant analysis was employed to compare cytokine profiles.
• * Participants hospitalized for breakthrough dengue were analyzed, including stratification by age (<9 years vs. ≥9 years).

Main Results:

• * No significant differences were found in the overall cytokine profiles between CYD-TDV and placebo recipients hospitalized for breakthrough dengue.
• * Stratification by age did not reveal any differences in cytokine profiles for breakthrough dengue.
• * The cytokine analysis did not identify any specific immune signature associated with CYD-TDV vaccination in hospitalized dengue cases.

Conclusions:

• * The recombinant dengue vaccine (CYD-TDV) does not appear to induce a distinct cytokine profile compared to placebo.
• * These findings corroborate the observed clinical safety profile of the CYD-TDV vaccine.
• * The study provides exploratory insights into the immunological response to CYD-TDV in the context of breakthrough dengue infections.