ABSTRACT
BACKGROUND: Dengue human infection models (DHIM) have been used as a safe means to test the viability of prophylaxis and therapeutics. METHODS: A phase 1 study of 12 healthy adult volunteers using a challenge virus, DENV-1-LVHC strain 45AZ5, was performed. A dose escalating design was used to determine the safety and performance profile of the challenge virus. Subjects were evaluated extensively until 28 days and then out to 6 months. RESULTS: Twelve subjects received the challenge virus: 6 with 0.5 mL of 6.5 × 103 plaque-forming units (PFU)/mL (low-dose group) and 6 with 0.5 mL of 6.5 × 104 PFU/mL (mid-dose group). All except 1 in the low-dose group developed detectable viremia. For all subjects the mean incubation period was 5.9 days (range 5-9 days) and mean time of viremia was 6.8 days (range 3-9 days). Mean peak for all subjects was 1.6 × 107 genome equivalents (GE)/mL (range 4.6 × 103 to 5 × 107 GE/mL). There were no serious adverse events or long-term safety signals noted. CONCLUSIONS: We conclude that DENV-1-LVHC was well-tolerated, resulted in an uncomplicated dengue illness, and may be a suitable DHIM for therapeutic and prophylactic product testing. CLINICAL TRIALS REGISTRATION: NCT02372175.
Subject(s)
Dengue Vaccines/immunology , Dengue Virus/immunology , Dengue/prevention & control , Vaccines, Virus-Like Particle/immunology , Dengue/immunology , Dengue/virology , Dengue Vaccines/administration & dosage , Dengue Vaccines/adverse effects , Healthy Volunteers , Humans , Outcome Assessment, Health Care , Vaccination , Vaccines, Virus-Like Particle/administration & dosage , Vaccines, Virus-Like Particle/adverse effects , Viremia/immunology , Viremia/prevention & control , Viremia/virologyABSTRACT
BACKGROUND: Dengue is a global health problem requiring an effective, safe dengue vaccine. METHODS: We report the results of a phase II, randomized, open-label, single-center trial in adults aged 18 to 45 years in the United States designed to explore the effects of the Chimeric Yellow Fever Derived Tetravalent Dengue Vaccine (CYD-TDV, Dengvaxia) when administered on its designated schedule (months 0, 6, and 12) or on an accelerated dosing schedule (months 0, 2, and 6) and/or given before, or concomitantly with, a vaccine against Japanese encephalitis (JE). RESULTS: Based on dengue virus serotype-specific neutralizing antibody (NAb), the accelerated dosing schedule was comparable to the 0, 6, and 12-month schedule. Giving JE vaccine concurrently with CYD-TDV did not result in an increase in overall NAb titers. Immunophenotyping of peripheral blood mononuclear cells revealed an increase in activated CD8+ T cells after CYD-TDV vaccination, a phenomenon that was greatest for the JE vaccine primed. CONCLUSIONS: We conclude that an accelerated dosing schedule of CYD-TDV results in essentially equivalent dengue serotype-specific NAb titers as the currently used schedule, and there may be an early benefit in antibody titers and activated CD8+ T cells by the administration of the JE vaccine before CYD-TDV vaccination.
Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Dengue Vaccines/administration & dosage , Japanese Encephalitis Vaccines/administration & dosage , Adolescent , Adult , Dengue Vaccines/adverse effects , Dengue Vaccines/immunology , Female , Humans , Immunization Schedule , Immunophenotyping , Japanese Encephalitis Vaccines/adverse effects , Japanese Encephalitis Vaccines/immunology , Male , Middle Aged , Young AdultABSTRACT
Los objetivos de este informe son: garantizar las condiciones adecuadas de salud, higiene seguridad en el ambiente laboral. Lograr un ambiente de trabajo desprovisto de riesgos para la salud psicofísica de los trabajadores. Proteger a las personas y al medio ambiente en general contra los riesgos que directamente afectan a la salud, la seguridad y el equilibrio ecológico
