RESUMO
El dengue es una enfermedad viral transmitida por la picadura del mosquito Aedes aegypti. El comportamiento del dengue en Argentina es epidémico; la mayoría de los casos se observan en los meses de mayor temperatura. Hasta la semana epidemiológica (SE) 20/2023, se registraron en Argentina 106 672 casos; se vieron afectadas 18 de las 24 provincias que conforman el país. Dentro de los principales grupos de riesgo, se incluyen los menores de 2 años. Reconocer los signos, síntomas e identificar los factores de riesgo es fundamental para el manejo de casos con mayor riesgo de gravedad. Presentamos el caso de una paciente de 32 días de vida que se internó por síndrome febril sin foco, con diagnósticos diferenciales de meningitis viral y sepsis, evolucionó con leucocitosis, plaquetopenia, hipoalbuminemia, asociado a exantema y edemas. Se llegó al diagnóstico de dengue por la clínica, epidemiologia e IgM positiva.
Dengue fever is a viral disease transmitted by the Aedes aegypti mosquitoes. In Argentina, dengue fever is an epidemic disease; most cases are reported during the hot months.Until epidemiological week (EW) 20/2023, 106 672 cases were reported across 18 of the 24 provinces of Argentina. Children younger than 2 years are among the main groups at risk. Recognizing signs and symptoms and identifying risk factors is fundamental for the management of cases at a higher risk of severity. Here we describe the case of a 32-day-old female patient who was hospitalized due to febrile syndrome without a source, who had a differential diagnosis of viral meningitis and sepsis and progressed to leukocytosis, thrombocytopenia, hypoalbuminemia in association with rash and edema. The diagnosis of dengue fever was established based on clinical, epidemiological, and positive IgM data.
Assuntos
Humanos , Animais , Feminino , Lactente , Aedes , Dengue/complicações , Dengue/diagnóstico , Dengue/epidemiologia , Argentina , Fatores de Risco , Diagnóstico DiferencialRESUMO
Dengvaxia is the first dengue vaccine recommended in the United States (U.S.). It is recommended for children aged 9-16 y with laboratory-confirmed previous dengue infection and living in areas where dengue is endemic. We conducted focus groups with parents and in-depth interviews with key informants (i.e. practicing pediatricians, physicians from immunization clinics, university researchers, and school officials) in Puerto Rico (P.R.) to examine acceptability, barriers, and motivators to vaccinate with Dengvaxia. We also carried out informal meetings and semi-structured interviews to evaluate key messages and educational materials with pediatricians and parents. Barriers to vaccination included lack of information, distrust toward new vaccines, vaccine side effects and risks, and high cost of/lack of insurance coverage for laboratory tests and vaccines. Motivators included clear information about the vaccine, a desire to prevent future dengue infections, the experience of a previous dengue infection or awareness of dengue fatality, vaccine and laboratory tests covered by health insurance, availability of rapid test results and vaccine appointments. School officials and parents agreed parents would pay a deductible of $5-20 for Dengvaxia. For vaccine information dissemination, parents preferred an educational campaign through traditional media and social media, and one-on-one counseling of parents by healthcare providers. Education about this vaccine to healthcare providers will help them answer parents' questions. Dengvaxia acceptability in P.R. will increase by addressing motivators and barriers to vaccination and by disseminating vaccine information in plain language through spokespersons from health institutions in P.R.
Assuntos
Vacinas contra Dengue , Dengue , Vacinas , Criança , Humanos , Dengue/prevenção & controle , Vacinas contra Dengue/efeitos adversos , Pais , Porto Rico/epidemiologia , Estados Unidos , Vacinação/métodos , AdolescenteRESUMO
Dengue fever is a viral disease transmitted by the Aedes aegypti mosquitoes. In Argentina, dengue fever is an epidemic disease; most cases are reported during the hot months. Until epidemiological week (EW) 20/2023, 106 672 cases were reported across 18 of the 24 provinces of Argentina. Children younger than 2 years are among the main groups at risk. Recognizing signs and symptoms and identifying risk factors is fundamental for the management of cases at a higher risk of severity. Here we describe the case of a 32-day-old female patient who was hospitalized due to febrile syndrome without a source, who had a differential diagnosis of viral meningitis and sepsis and progressed to leukocytosis, thrombocytopenia, hypoalbuminemia in association with rash and edema. The diagnosis of dengue fever was established based on clinical, epidemiological, and positive IgM data.
El dengue es una enfermedad viral transmitida por la picadura del mosquito Aedes aegypti. El comportamiento del dengue en Argentina es epidémico; la mayoría de los casos se observan en los meses de mayor temperatura. Hasta la semana epidemiológica (SE) 20/2023, se registraron en Argentina 106 672 casos; se vieron afectadas 18 de las 24 provincias que conforman el país. Dentro de los principales grupos de riesgo, se incluyen los menores de 2 años. Reconocer los signos, síntomas e identificar los factores de riesgo es fundamental para el manejo de casos con mayor riesgo de gravedad. Presentamos el caso de una paciente de 32 días de vida que se internó por síndrome febril sin foco, con diagnósticos diferenciales de meningitis viral y sepsis, evolucionó con leucocitosis, plaquetopenia, hipoalbuminemia, asociado a exantema y edemas. Se llegó al diagnóstico de dengue por la clínica, epidemiologia e IgM positiva.
Assuntos
Aedes , Dengue , Criança , Animais , Humanos , Feminino , Dengue/complicações , Dengue/diagnóstico , Dengue/epidemiologia , Fatores de Risco , Diagnóstico Diferencial , ArgentinaRESUMO
The occurrence of dengue disease has increased radically in recent decades. Previously, we constructed the pE1D2 and pcTPANS1 DNA vaccines encoding the DENV2 envelope (E) and non-structural 1 (NS1) proteins, respectively. To decrease the number of plasmids in a tetravalent candidate vaccine, we constructed a bicistronic plasmid, pNS1/E/D2, encoding these two proteins simultaneously. We evaluated the protective immunity induced in mice vaccinated with the pNS1/E/D2 candidate and compared to the responses elicited by immunization with the former vaccines isolated or in combination. We transfected BHK-21 cells with the different plasmids and detected recombinant proteins by immunofluorescence and mass spectrometry assays to confirm antigen expression. BALB/c mice were inoculated with the DNA vaccines followed by a lethal DENV2 challenge. ELISA, PRNT50, and IFN-gamma ELISPOT assays were performed for the investigation of the humoral and cellular responses. We observed the concomitant expression of NS1 and E proteins in pNS1/E/D2-transfected cells. All E-based vaccines induced anti-E and neutralizing antibodies. However, anti-NS1 antibodies were only observed after immunization with the pcTPANS1 administered alone or combined with pE1D2. In contrast, splenocytes from pNS1/E/D2- or pcTPANS1 + pE1D2-vaccinated animals responded to NS1- and E-derived synthetic peptides. All the DNA vaccines conferred protection against DENV2.
Assuntos
Vacinas contra Dengue , Vírus da Dengue , Dengue , Vacinas de DNA , Animais , Anticorpos Antivirais , Dengue/prevenção & controle , Vacinas contra Dengue/genética , Vírus da Dengue/genética , Imunidade , Camundongos , Camundongos Endogâmicos BALB C , Vacinas de DNA/genética , Proteínas não Estruturais Virais/genéticaRESUMO
An effective vaccine against the dengue virus (DENV) should induce a balanced, long-lasting antibody (Ab) response against all four viral serotypes. The burst of plasmablasts in the peripheral blood after vaccination may reflect enriched vaccine-specific Ab secreting cells. Here we characterize the acute plasmablast responses from naïve and DENV-exposed individuals following immunization with the live attenuated tetravalent (LAT) Butantan DENV vaccine (Butantan-DV). The frequency of circulating plasmablasts was determined by flow cytometric analysis of fresh whole blood specimens collected from 40 participants enrolled in the Phase II Butantan-DV clinical trial (NCT01696422) before and after (days 6, 12, 15 and 22) vaccination. We observed a peak in the number of circulating plasmablast at day 15 after vaccination in both the DENV naïve and the DENV-exposed vaccinees. DENV-exposed vaccinees experienced a significantly higher plasmablast expansion. In the DENV-naïve vaccinees, plasmablasts persisted for approximately three weeks longer than among DENV-exposed volunteers. Our findings indicate that the Butantan-DV can induce plasmablast responses in both DENV-naïve and DENV-exposed individuals and demonstrate the influence of pre-existing DENV immunity on Butantan DV-induced B-cell responses.
Assuntos
Vacinas contra Dengue , Vírus da Dengue , Anticorpos Antivirais , Brasil , Humanos , Vacinas AtenuadasRESUMO
An effective vaccine against the dengue virus (DENV) should induce a balanced, long-lasting antibody (Ab) response against all four viral serotypes. The burst of plasmablasts in the peripheral blood after vaccination may reflect enriched vaccine-specific Ab secreting cells. Here we characterize the acute plasmablast responses from naïve and DENV-exposed individuals following immunization with the live attenuated tetravalent (LAT) Butantan DENV vaccine (Butantan-DV). The frequency of circulating plasmablasts was determined by flow cytometric analysis of fresh whole blood specimens collected from 40 participants enrolled in the Phase II Butantan-DV clinical trial (NCT01696422) before and after (days 6, 12, 15 and 22) vaccination. We observed a peak in the number of circulating plasmablast at day 15 after vaccination in both the DENV naïve and the DENV-exposed vaccinees. DENV-exposed vaccinees experienced a significantly higher plasmablast expansion. In the DENV-naïve vaccinees, plasmablasts persisted for approximately three weeks longer than among DENV-exposed volunteers. Our findings indicate that the Butantan-DV can induce plasmablast responses in both DENV-naïve and DENV-exposed individuals and demonstrate the influence of pre-existing DENV immunity on Butantan DV-induced B-cell responses.
RESUMO
Dengue is endemic in several regions, and the global incidence is increasing. The recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) is recommended for dengue seropositive individuals ≥ 9 years. Human papillomavirus (HPV) vaccination is recommended for girls aged 9-14 years to prevent HPV infection-related cancers. This study assessed the immunogenicity and safety of a bivalent HPV (types 16 and 18) vaccine and CYD-TDV when co-administered concomitantly or sequentially. This was a Phase IIIb, randomized, open-label, multicenter study in girls aged 9-14 years in Mexico (NCT02979535). Participants were randomized 1:1 to receive three doses of CYD-TDV 6 months apart and two doses of bivalent HPV vaccine either concomitantly with, or 1 month before (sequentially), the first 2 CYD-TDV doses. Antibody levels were measured at baseline and 28-days after each vaccine dose for all participants, using an enzyme-linked immunosorbent assay for HPV-16 and HPV-18 antibodies, and a plaque reduction neutralization test for the four dengue serotypes; results are reported only for participants who were seropositive at baseline. Safety was assessed for all randomized participants throughout the study. Of the randomized participants, 305/478 (63.8%) were seropositive for dengue at baseline: 154 in the concomitant group and 151 in the sequential group. After the last HPV vaccine dose, the antibody titers for HPV were comparable in seropositive participants between treatment groups, with between group titer ratios of 0.966 for HPV-16 and 0.999 for HPV-18. After dose 3 of CYD-TDV, antibody titers were comparable for the concomitant and sequential groups across all serotypes, with between-group ratios close to 1 (serotype 1: 0.977; serotype 2: 0.911; serotype 3: 0.921; serotype 4: 0.931). CYD-TDV and a bivalent HPV vaccine administered concomitantly or sequentially in dengue seropositive girls aged 9-14 years elicited comparable immune responses with similar safety profiles.
Assuntos
Vacinas contra Dengue , Dengue , Vacinas contra Papillomavirus , Anticorpos Antivirais , Dengue/prevenção & controle , Vacinas contra Dengue/efeitos adversos , Feminino , Humanos , Imunogenicidade da Vacina , México , Vacinas contra Papillomavirus/efeitos adversos , Vacinas CombinadasRESUMO
Dengue disease represents a large and growing global threat to public health, causing a significant burden to health systems of endemic countries. For countries considering vaccination as part of their Integrated Management Strategy for Prevention and Control of Dengue, the World Health Organization currently recommends the first licensed dengue vaccine, CYD-TDV for: individuals aged 9â¯years or above from populations with high transmission rates, based on either seroprevalence criteria or pre-vaccination screening strategies, and for persons with confirmed prior exposure to infection in moderate to lower transmission settings. This paper describes the main conclusions of the Sixth Meeting of the International Dengue Initiative (IDI) held in June 2018, following release of a new product label by the manufacturer, updated WHO-SAGE recommendations, additional scientific evidence on vaccine performance, and reports of experiences by implementing countries. Considerations were made regarding the need for improving the quality of epidemiological and surveillance data in the region to help define the convenience of either of the two vaccination strategies recommended by WHO-SAGE. Extensive discussion was dedicated to the pros and cons of implementing either of such strategies in Latin America. Although, in general, a seroprevalence-based approach was preferred in high transmission settings, when cost-effectivity is favorable pre-vaccination screening is a convenient alternative. Cost-effectiveness evaluations can assist with the decisions by public health authorities of whether to introduce a vaccine. Where implemented, vaccine introduction should be part of a public health strategy that includes the participation of multiple sectors of society, incorporating input from scientific societies, ministries of heath, and civil society, while ensuring a robust communication program.
Assuntos
Vacinas contra Dengue/administração & dosagem , Dengue/prevenção & controle , Implementação de Plano de Saúde/organização & administração , Saúde Pública , Congressos como Assunto , Análise Custo-Benefício , Dengue/epidemiologia , Implementação de Plano de Saúde/estatística & dados numéricos , Humanos , Internacionalidade , América Latina/epidemiologia , Peru , Estudos Soroepidemiológicos , Organização Mundial da SaúdeRESUMO
BACKGROUND: The background incidence of viscerotropic- (VLD) and neurotropic-like disease (NLD) unrelated to immunization in dengue-endemic countries is currently unknown. METHODS: This retrospective population-based analysis estimated crude and standardized incidences of VLD and NLD in twelve hospitals in Brazil (nâ¯=â¯3), Mexico (nâ¯=â¯3), and Malaysia (nâ¯=â¯6) over a 1-year period before the introduction of the tetravalent dengue vaccine. Catchment areas were estimated using publicly available population census information and administrative data. The denominator population for incidence rates was calculated, and sensitivity analyses assessed the impact of important assumptions. RESULTS: Total cases adjudicated as definite VLD were 5, 57, and 56 in Brazil, Mexico, and Malaysia, respectively. Total cases adjudicated as definite NLD were 103, 29, and 26 in Brazil, Mexico, and Malaysia, respectively. Crude incidence rates of cases adjudicated as definite VLD in Brazil, Mexico, and Malaysia were 1.17, 2.60, and 1.48 per 100,000 person-years, respectively. Crude incidence rates of cases adjudicated as definite NLD in Brazil, Mexico, and Malaysia were 4.45, 1.32, and 0.69 per 100,000 person-years, respectively. CONCLUSIONS: Background incidence estimates of VLD and NLD obtained in Mexico, Brazil, and Malaysia could provide context for cases occurring after the introduction of the tetravalent dengue vaccine.
Assuntos
Vacinas contra Dengue/efeitos adversos , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Criança , Pré-Escolar , Vacinas contra Dengue/administração & dosagem , Vacinas contra Dengue/imunologia , Feminino , Humanos , Incidência , Lactente , Malásia/epidemiologia , Masculino , Programas de Rastreamento , México/epidemiologia , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Vigilância da População , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The dengue vaccination era began when Dengvaxia (CYD-TDV) became available in 2016. In addition, several second-generation vaccine candidates are currently in phase 3 trials, suggesting that a broader availability of dengue vaccines may be possible in the near future. Advancing on the recent WHO-SAGE recommendations for the safe and effective use of CYD-TDV at the regional level on average, this study investigates the vaccination impacts and cost-effectiveness of CYD-TDV and of a hypothetical new vaccine candidate (NVC) in a country-specific manner for three endemic countries: Vietnam, Thailand, and Colombia. METHODS: The vaccination impacts of CYD-TDV and NVC were derived by fitting the empirical seroprevalence rates of 9â¯year olds into an individual-based meta-population transmission model, previously used for the WHO-SAGE working group. The disability-adjusted life years were estimated by applying country-specific parametric values. The cost-effectiveness analyses of four intervention strategies in combination with routine and catch-up campaigns were compared for both vaccines to inform decision makers regarding the most suitable immunization program in each of the three countries. RESULTS AND CONCLUSION: Both CYD-TDV and NVC could be cost-effective at the DALY threshold cost of $2000 depending upon vaccination costs. With CYD-TDV, targeting 9â¯year olds in routine vaccination programs and 10-29â¯year olds as a one-off catch-up campaign was the most cost-effective strategy in all three countries. With NVC, while the most cost-effective strategy was to vaccinate 9-29 and 9-18â¯year olds in Vietnam and Thailand respectively, vaccinating younger age cohorts between 1 and 5â¯years old in Colombia was more cost-effective than other strategies. Given that three countries will soon face decisions regarding whether and how to incorporate CYD-TDV or future dengue vaccines into their budget-constrained national immunization programs, the current study outcomes can be used to help decision makers understand the expected impacts and cost-effectiveness of such vaccines.
Assuntos
Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Vacinas Atenuadas/imunologia , Colômbia , Análise Custo-Benefício/métodos , Humanos , Programas de Imunização/métodos , Estudos Soroepidemiológicos , Tailândia , Vacinação/métodos , VietnãRESUMO
OBJECTIVE: Our objective was to describe the risk of hospital admission for virologically confirmed dengue (VCD) and the risk of clinically severe hospitalized VCD occurring up to 4 years after the first dose (years 1 to 4) in three randomized clinical trials comparing tetravalent dengue vaccine with placebo. METHODS: The relative risks (RR) for hospitalized VCD from first dose to year 4 were estimated by year and age-group in individual and combined studies. RESULTS: Overall, from Year 1 to Year 4, 233 and 228 participants had at least one episode of hospitalized VCD in the vaccinated (n = 22 603) and placebo (n = 11 301) groups, respectively (RR = 0.511, 95% CI 0.42-0.62). Among these, 48 and 47 cases, respectively, were classified as clinically severe. In children aged ≥9 years, 88 and 136 participants had at least one episode of hospitalized VCD in the vaccinated (n = 17 629) and placebo (n = 8821) groups, respectively (RR = 0.324; 95% CI 0.24-0.43). In vaccinated participants aged <9 years, particularly in those aged 2-5 years, there were more hospitalized VCD cases compared with the control participants in Year 3 but not in Year 4. The overall RR in those aged <9 years for Year 1 to Year 4 was 0.786 (95% CI 0.60-1.03), with a higher protective effect in the 6-8 year olds than in the 2-5 year olds. CONCLUSIONS: The overall benefit-risk remained positive in those aged ≥9 years up to year 4, although the protective effect was lower in years 3 and 4 than in years 1 and 2.
Assuntos
Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Dengue/prevenção & controle , Vacinas Atenuadas/imunologia , Adolescente , Anticorpos Antivirais/sangue , Ásia/epidemiologia , Criança , Pré-Escolar , Dengue/epidemiologia , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , América Latina/epidemiologia , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Sorogrupo , ViremiaRESUMO
BACKGROUND: Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. METHODS: The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. RESULTS: Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. CONCLUSIONS: Despite the recent licensure of the CYD-TDV dengue vaccine in some countries, results from the vaccine's phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.
Assuntos
Formação de Anticorpos , Vacinas contra Dengue/imunologia , Dengue/prevenção & controle , Nanotubos de Carbono/química , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Proliferação de Células , Citocinas/imunologia , Dengue/imunologia , Vacinas contra Dengue/uso terapêutico , Vírus da Dengue/imunologia , Feminino , Imunidade Celular , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Nanoconjugados/química , Nanomedicina , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Análise Espectral Raman , Baço/citologia , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/uso terapêuticoRESUMO
Dengue is no longer restricted to tropical developing countries, but is now a major global public health problem. Despite the recent license approval of the CYD-TDV vaccine in some countries, efforts to develop a more efficient vaccine against Dengue virus (DENV) continue. Herein, we evaluate the immunogenicity and level of protection of two potential vaccines against DENV based on recombinant modified vaccinia virus Ankara (rMVA). The vaccine addressing the Envelope protein from DENV serotype 3 to the endoplasmic reticulum elicited neutralizing antibodies titers which correlate with protection, and also confers protection upon challenge in a mouse model. Our results support the development of a tetravalent dengue vaccine with the further construction of rMVAs expressing proteins from the other DENV serotypes.
Assuntos
Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Dengue/prevenção & controle , Portadores de Fármacos , Encefalite Viral/prevenção & controle , Vaccinia virus/genética , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vacinas contra Dengue/administração & dosagem , Vacinas contra Dengue/genética , Vírus da Dengue/genética , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Envelope Viral/genéticaRESUMO
Dengue is the most important arbovirus disease throughout the world and it is responsible for more than 500,000 dengue hemorrhagic cases and 22,000 deaths every year. One vaccine was recently licensed for human use in Brazil, Mexico and Philippines and although at least seven candidates have been in clinical trials the results of the most developed CYD vaccine have demonstrated immunization problems, such as uneven protection and interference between serotypes. We constructed a vaccine candidate based on vesicular stomatitis virus (VSV) expression of pre-membrane (prM) and envelope (E) proteins of dengue-2 virus (DENV-2) and tested it in mice to evaluate immunogenicity and protection against DENV-2 infection. VSV has been successfully used as vaccine vectors for several viruses to induce strong humoral and cellular immune responses. The VSV-DENV-2 recombinant was constructed by inserting the DENV-2 structural proteins into a VSV plasmid DNA for recombinant VSV-DENV-2 recovery. Infectious recombinant VSV viruses were plaque purified and prM and E expression were confirmed by immunofluorescence and radiolabeling of proteins of infected cells. Forty Balb/C mice were inoculated through subcutaneous (s.c.) route with VSV-DENV-2 vaccine in a two doses schedule 15 d apart and 29 d after first inoculation, sera were collected and the mice were challenged with 50 lethal doses (LD50) of a neurovirulent DENV-2. The VSV-DENV-2 induced anti-DENV-2 antibodies and protected animals in the challenge experiment comparable to DENV-2 immunization control group. We conclude that VSV is a promising platform to test as a DENV vaccine and perhaps against others Flaviviridae.
Assuntos
Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Dengue/prevenção & controle , Portadores de Fármacos , Vetores Genéticos , Vesiculovirus/genética , Animais , Anticorpos Antivirais/sangue , Vacinas contra Dengue/administração & dosagem , Vacinas contra Dengue/genética , Vírus da Dengue/genética , Modelos Animais de Doenças , Leucócitos Mononucleares/imunologia , Camundongos Endogâmicos BALB C , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Proteínas Estruturais Virais/genética , Proteínas Estruturais Virais/imunologiaRESUMO
BACKGROUND: A safe, effective tetravalent dengue vaccine is a global health priority. The safety and immunogenicity of a live attenuated, recombinant tetravalent dengue vaccine candidate (TDV) were evaluated in healthy volunteers from dengue-endemic countries. METHODS: This multicenter, double-blind, phase 2 study was conducted in Puerto Rico, Colombia, Singapore, and Thailand. During stage I, 148 volunteers aged 1.5-45 years were sequentially enrolled into 4 age-descending groups and randomized at a ratio of 2:1 to receive TDV or placebo. In stage II (group 5), 212 children aged 1.5-11 years were randomized at a ratio of 3:1 to receive TDV or placebo. Participants received a subcutaneous injection of TDV or placebo on days 0 and 90 and were followed for analysis of safety, seropositivity, and neutralizing antibodies to DENV-1-4. RESULTS: Injection site pain, itching, and erythema (mostly mild) were the only solicited adverse events more frequently reported with TDV than with placebo in all age groups. After 2 TDV doses, seropositivity was >95% in all 5 groups for DENV-1-3 and 72.7%-100% for DENV-4; geometric mean titers ranged from 582 to 1187 for DENV-1, from 582 to 1187 for DENV-2, from 196 to 630 for DENV-3, and from 41 to 210 for DENV-4 among the 5 groups. CONCLUSIONS: TDV was well tolerated and immunogenic in volunteers aged 1.5-45 years, irrespective of prevaccination dengue exposure.
Assuntos
Anticorpos Antivirais/imunologia , Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Dengue/prevenção & controle , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Criança , Pré-Escolar , Colômbia , Dengue/imunologia , Vacinas contra Dengue/administração & dosagem , Vacinas contra Dengue/normas , Método Duplo-Cego , Feminino , Humanos , Lactente , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Porto Rico , Segurança , Singapura , Tailândia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/normas , Adulto JovemRESUMO
Butantan Institute is a public Brazilian biomedical research-manufacturer center affiliated to the São Paulo State Secretary of Health. Currently, Butantan is one of the main public producers of vaccines, antivenoms, and antitoxins in Latin America. The partnership between Butantan and the National Institutes of Health (NIH) of the United Sates has been one of the longest and most successful partnerships in the development and manufacturing of new vaccines. Recently, Butantan Institute has developed and manufactured a lyophilized tetravalent live attenuated dengue vaccine with the four dengue viruses attenuated and licensed from the Laboratory of Infectious Diseases at The National Institutes of Allergy and Infectious Diseases (LID/NIAID/NIH). The objective of this paper is to describe the clinical evaluation strategies of a live attenuated tetravalent dengue vaccine (Butantan-DV) developed and manufactured by Butantan Institute. These clinical strategies will be used to evaluate the Butantan-DV Phase III trial to support the Butantan-DV licensure for protection against any symptomatic dengue caused by any serotype in people aged 2 to 59 years.
Assuntos
Ensaios Clínicos como Assunto , Vacinas contra Dengue/imunologia , Vacinas contra Dengue/isolamento & purificação , Dengue/prevenção & controle , Brasil , Dengue/epidemiologia , Vacinas contra Dengue/efeitos adversos , Vacinas contra Dengue/genética , Humanos , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/isolamento & purificaçãoRESUMO
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.