Keywords

Dengue Virus; Inactivated Dengue Vaccines; Inactivated Vaccine; Antibody-dependent Enhancement Safety; Immunocompromised; Tetravalent Dengue Purified Inactivated Vaccine; Vaccine Safety

Abstract

Dengue virus is a mosquito-borne flavivirus responsible for over 390 million annual cases worldwide. While there are live-attenuated vaccines available to prevent dengue, none are currently approved for use in the United States, and existing platforms pose significant risks of viral reactivation and antibody-dependent enhancement in vulnerable populations, such as pregnant women, children under the age of nine, and the immunocompromised. This widespread exclusion of vulnerable populations exposes a significant vaccine equity gap in dengue prevention, as the populations most at risk for severe dengue are the same ones who are currently excluded from vaccination. In this study, I conducted the first quantitative meta-analysis to evaluate the safety and efficacy of inactivated dengue vaccines. I systematically extracted data from clinical trials, including serious adverse events, adverse events, and nucleic acid test (NAT)- ­­­­­confirmed symptomatic dengue cases. Statistical analyses were performed using Review Manager software to calculate pooled risk ratios (RR) and corresponding confidence intervals.

This meta-analysis indicated a superior safety profile for the inactivated dengue vaccine platform, with a statistically significant reduction in adverse events compared to placebo (risk ratio [RR]= 0.72, P = 0.04) and zero reported cases in antibody-dependent enhancement or viral reactivation. Regarding efficacy, the analysis utilized n events and N populations to contrast the vaccine platforms. Inactivated vaccine clinical trials reported zero symptomatic infections (n=0) across a combined population of approximately 240 participants. This is primarily due to the study being conducted in non-endemic regions. This was compared to live-attenuated clinical trials, which provided a larger-scale population with over 23,000 participants. The limited studies of inactivated dengue vaccine trials restrict the statistical power to calculate a pooled infection risk ratio, however qualitative findings display inactivated platforms induce a higher CD4+ T cell response compared to a CD8+ T cell response. This qualitative finding suggests that while inactivated vaccines are a safer alternative for vulnerable groups, further phase 3 trials in endemic regions are required to establish their long-term efficacy.

Thesis Completion Year

2026

Thesis Completion Semester

Spring

Thesis Chair

Earnest, James

Department

Biomedical Sciences

Thesis Discipline

Biomedical Sciences

Language

English

Access Status

Open Access

Length of Campus Access

5 years

Campus Location

Orlando (Main) Campus

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