RESUMEN
UNLABELLED: Several ChimeriVax-Dengue (CYD)-based vaccination strategies were investigated as potential alternatives to vaccination with tetravalent CYD vaccine (CYD-TDV) in this phase IIa trial conducted in 2008-9 in 150 healthy adults. Participants were randomized and vaccinated on D0 and D105 (± 15 days). One group received bivalent CYD vaccine against serotypes 1 and 3 (CYD-1;3) on day 0 and CYD-2;4 on day 105 (± 15 days). Two groups received an injection at each timepoint of a tetravalent blend of CYD-1;3;4 and a VERO cell derived, live attenuated vaccine against serotype 2 (VDV-2), or the reference CYD-TDV. A fourth group received Japanese encephalitis (JE) vaccine on days -14, -7 and 0, followed by CYD-TDV on day 105. Viraemia was infrequent in all groups. CYD-4 viraemia was most frequent after tetravalent vaccination, while CYD-3 viraemia was most frequent after the first bivalent vaccination. Immunogenicity as assessed by 50% plaque reduction neutralisation test on D28 was comparable after the first injection of either tetravalent vaccine, and increased after the second injection, particularly with the blended CYD-1;3;4/ VDV-2 vaccine. In the bivalent vaccine group, immune response against serotype 3 was highest and the second injection elicited a low immune response against CYD 2 and 4. Immune responses after the first injection of CYD-TDV in the JE-primed group were in general higher than after the first injection in the other groups. All tested regimens were well tolerated without marked differences between groups. Bivalent vaccination showed no advantage in terms of immunogenicity. CLINICAL TRIAL REGISTRATION NUMBER: NCT00740155.
Asunto(s)
Anticuerpos Antivirales/sangre , Vacunas contra el Dengue/inmunología , Virus del Dengue/inmunología , Dengue/inmunología , Viremia/sangre , Adolescente , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Dengue/prevención & control , Vacunas contra el Dengue/efectos adversos , Vacunas contra el Dengue/uso terapéutico , Femenino , Humanos , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Vacunas contra la Encefalitis Japonesa/efectos adversos , Vacunas contra la Encefalitis Japonesa/inmunología , Vacunas contra la Encefalitis Japonesa/uso terapéutico , Masculino , México , Pruebas de Neutralización , Vacunación , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/uso terapéutico , Viremia/inmunología , Vacunas contra el Virus del Nilo Occidental/efectos adversos , Vacunas contra el Virus del Nilo Occidental/inmunología , Vacunas contra el Virus del Nilo Occidental/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Preliminary results in healthy, young US adults showed that a tetravalent, live-attenuated dengue vaccine (TDV) was safe and immunogenic, but no data are available in children. METHODS: In a multicenter, randomized, controlled, observer-blinded study in the city of Mexico, children aged 2 to 5, 6 to 11, and 12 to 17 years (36 children per age group), and adults (n = 18) aged <45 years received the following: 3 injections of TDV at months 0, 3.5, and 12 (TDV-TDV-TDV), or 1 injection of yellow fever vaccine (YF) at month 0, and 2 injections of TDV at months 3.5 and 12 (YF-TDV-TDV). Adverse events and biologic safety (biochemistry and hematology) were documented. Plaque reduction neutralization test (PRNT50) antibody titers against the TDV parental viruses were measured 28 days after vaccination. Seropositivity was defined as antibody titers ≥10 1/dil. RESULTS: No vaccine-related serious adverse events, other significant clinical adverse events, or clinically significant trends in biologic safety were observed. Reactogenicity did not increase with successive TDV injections, and mild-to-moderate injection site pain, headache, myalgia, and malaise were most commonly reported (14%-40% after each vaccination). After 3 TDV vaccinations, the seropositivity rate against each dengue serotype was in the range 77% to 92%, compared with 85% to 94% after completion of the YF-TDV-TDV regimen. Of the 2- to 11-year-old participants, 95% were seropositive against ≥3 serotypes after 3 vaccinations. CONCLUSIONS: A 3-dose TDV regimen had a favorable safety profile in children and adults and elicited neutralizing antibody responses against all 4 serotypes. These findings support the continued development of this vaccine.
Asunto(s)
Vacunas contra el Dengue/efectos adversos , Vacunas contra el Dengue/inmunología , Dengue/prevención & control , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Adolescente , Adulto , Niño , Preescolar , Dengue/inmunología , Vacunas contra el Dengue/administración & dosificación , Femenino , Humanos , Masculino , México , Vacunas Atenuadas/administración & dosificación , Viremia , Vacuna contra la Fiebre Amarilla/administración & dosificación , Adulto JovenRESUMEN
Este artigo é uma revisão sobre o desenvolvimento de uma vacina candidata tetravalente contra a dengue (VTD) composta por 4 cepas recombinantes vivas atenuadas de vírus da dengue. Cada cepa expressa os genes da pré-membrana (prM) e do envelope de um dos quatro sorotipos do vírus da dengue e tem como base a cepa da vacina febre amarela 17D (YF17D). Os estudos pré-clínicos demonstraram que as cepas da VTD são estáveis genética e fenotipicamente, não hepatotrópicas, menos neurovirulentas do que a cepa YF 17D e não infectam mosquitos pela via oral. A VTD induz estimulação controlada das células dendríticas humanas e respostas imunes significantes...
The Sanofi Pasteur tetravalent dengue vaccine candidate is composed of 4 recombinant live attenuated vaccines based on a yellow fever vaccine 17D (YFV 17D) backbone, each expressing the prM and envelope genes of one of the four dengue virus serotypes. Pre-clinical studies have demonstrated that the TV dengue vaccine is genetically and phenotypically stable, non-hepatotropic, less neurovirulent than YFV 17D and does not infect mosquitoes by the oral route. In vitro and in vivo preclinical studies also showed that the TV dengue vaccine induced controlled stimulation in human dendritic cells, and significant immune responses in monkeys. TV dengue vaccine reactogenicity, viraemia induction and antibody responses were investigated in three Phase I trials in the USA, the Philippines and Mexico, in a two or three-dose regimen over a 12 month period...
Asunto(s)
Masculino , Femenino , Humanos , Preescolar , Niño , Adulto Joven , Adulto , Vacunas contra el Dengue/inmunología , Virus del Dengue , Flavivirus/inmunología , Inmunización , VacunasRESUMEN
Early diagnosis of dengue is challenging because the initial symptoms are often non-specific, viraemia may be below detectable levels and serological tests confirm dengue late in the course of illness. Identifying dengue early in the clinical course could be useful in reducing dengue virus transmission in a community. This study analyzed data from 145 laboratory-positive and 293 laboratory-negative dengue cases in Puerto Rico to define the early clinical features of dengue infection in children and adults and to identify the clinical features that predict a laboratory-positive dengue infection. Among children, rash and age were independently associated with laboratory-positive dengue infection. Rash in the absence of cough had a positive predictive value of 100% and a negative predictive value of 82.4% as a paediatric dengue screen. Among adults, eye pain, diarrhoea and absence of upper respiratory symptoms were independently associated with laboratory-positive dengue infection. No useful early predictors of dengue infection among adults were found. Using clinical features may promote earlier identification of a subset of paediatric dengue patients in Puerto Rico. Laboratory confirmation is still necessary for the accurate diagnosis of dengue infection.
Asunto(s)
Dengue/diagnóstico , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Dengue/epidemiología , Dengue/prevención & control , Diagnóstico Precoz , Humanos , Puerto Rico/epidemiologíaRESUMEN
From June 2005 to May 2006, a clinic-based enhanced surveillance system for dengue was implemented in a Puerto Rican municipality to provide a population-based measure of disease incidence and clinical outcomes. We obtained demographic and clinical information from suspected cases and performed serologic and virologic testing. We used World Health Organization (WHO) criteria to classify cases and applied a simplified case definition for severe dengue illness. There were 7.7 laboratory-positive cases of dengue per 1,000 population. The highest incidence, 13.4 per 1,000, was among 10 to 19 year olds. Of the 156 laboratory-positive cases, three patients (1.9%) met WHO criteria for dengue hemorrhagic fever, and 30 patients (19.2%) had at least one severe clinical manifestation of dengue infection. Our data suggest that in a community with endemic dengue, enhanced surveillance is useful for detecting symptomatic infections. Furthermore, the simplified case definition for severe dengue may be useful in clinic-based surveillance.