RESUMO
Four formulations of an investigational tetravalent dengue purified inactivated vaccine, administered as two doses one month (M) apart, were previously shown to be immunogenic and well-tolerated up to M13 of the phase I study NCT01702857. Here, we report results of the follow-up from M14 to year (Y) 3. One hundred healthy Puerto Rican adults, predominantly dengue virus (DENV)-primed, were randomized 1:1:1:1:1 to receive placebo or vaccine formulations: 1 µg/serotype/dose adjuvanted with aluminum, AS01E or AS03B, or aluminum-adjuvanted 4 µg/serotype/dose. No serious adverse events occurred. Two medically-attended potential immune-mediated disease cases, vaccination unrelated, were reported (groups 1 µg+Alum and 1 µg+AS03B). Of 14 instances of suspected dengue, none were laboratory confirmed. Geometric mean neutralizing antibody titers against DENV 1-4 waned from M14, but remained above pre-vaccination levels for DENV 1-3, with the highest values for group 1 µg+AS03B: 1220.1, 920.5, 819.4, and 940.5 (Y2), and 1329.3, 1169.2, 1219.8, and 718.9 (Y3). All formulations appeared to be safe and immunogenic during the 3-year follow-up.
Assuntos
Vacinas contra Dengue/uso terapêutico , Vírus da Dengue/imunologia , Dengue/prevenção & controle , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra Dengue/administração & dosagem , Vacinas contra Dengue/efeitos adversos , Vacinas contra Dengue/imunologia , Feminino , Seguimentos , Humanos , Masculino , Porto RicoRESUMO
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).