Abstract
.The safety and immunogenicity of four adjuvanted formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV) were evaluated in a predominantly dengue-primed population in Puerto Rico. In this placebo-controlled, randomized, observer-blind, phase I trial, 100 healthy adults were randomized 1:1:1:1:1 to receive DPIV at Day (D)0 and D28 (1 μg per dengue virus [DENV] type 1–4 adjuvanted with either alum, AS01E or AS03B, or 4 μg per DENV type adjuvanted with alum) or saline placebo. Functional antibody responses were assessed using a microneutralization assay at D56, Month (M)7, and M13. All DPIV formulations were well tolerated and no safety signals were identified through M13. The M13 according-to-protocol (ATP) immunogenicity cohort included 83 participants. The ATP analysis of immunogenicity was performed only on the 78 subjects seropositive for ≥ 1 DENV type at baseline: 69 tetravalent, three trivalent, two bivalent, and four monovalent. In all DPIV groups, geometric mean antibody titers (GMTs) increased from D0 to D56 and waned modestly through M13, while remaining well above prevaccination levels. The 4 μg + alum and the AS01E- and AS03B-adjuvanted formulations were highly immunogenic, with M13-neutralizing antibody GMTs against all four DENV types above 1,000. M13/D0 GMT ratios were highest in the 1 μg + AS03B group (ranging 3.2–3.7 depending on the DENV type). These results encourage continued clinical development of DPIV (ClinicalTrials.gov: NCT01702857).
Highlights
Dengue is a mosquito-borne viral disease found in tropical and subtropical climates worldwide
The safety and immunogenicity of four adjuvanted formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV) were evaluated in a predominantly dengue-primed population in Puerto Rico. In this placebo-controlled, randomized, observer-blind, phase I trial, 100 healthy adults were randomized 1:1:1:1:1 to receive DPIV at Day (D)[0] and D28 (1 μg per dengue virus [DENV] type 1–4 adjuvanted with either alum, AS01E or AS03B, or 4 μg per DENV type adjuvanted with alum) or saline placebo
M13/D0 geometric mean antibody titers (GMTs) ratios were highest in the 1 μg + AS03B group
Summary
Dengue is a mosquito-borne viral disease found in tropical and subtropical climates worldwide. Global dengue incidence has increased 30-fold in the last 50 years,[1] with 390 million dengue infections estimated to occur every year, of which 96 million are clinically apparent.[2] Dengue fever is endemic in Puerto Rico and transmission intensity varies geographically and by season.[3,4] A recent vaccine study in Puerto Rico found that the vast majority of young adults were seropositive for dengue and 89% of 21–50-year-olds were tetravalent seropositive.[5] In 2010, Puerto Rico experienced the largest dengue outbreak in its history, with more than 26,000 suspected cases reported.[3] endemic dengue cases are seen every year, cycles of epidemic outbreaks have been reported with increasing intensity during the last decades
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