RESUMO
We previously tested in monkeys the P64k-DomIII fusion protein of DEN-2 (PD5), combined with the serogroup A capsular polysaccharide (CPS-A) from N. meningitidis as an immunopotentiator. The results revealed the induction of neutralizing antibodies and partial protection after DEN-2 challenge. Since one formulation of the CPS-A was only evaluated in monkeys, in the present study, we evaluated two CPS-A-based formulations in mice. Animals immunized with PD5 in alum with the highest dose of CPS-A produced the highest levels of INF-γ secretion upon viral stimulation, and accordingly, 100% protection. This is the first report that describes the dose effect of CPS-A and its capacity to potentiate the cell-mediated immunity induced by a heterologous antigen in mice.
Assuntos
Cápsulas Bacterianas/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Dengue/prevenção & controle , Imunidade Celular , Neisseria meningitidis/imunologia , Regulação para Cima , Proteínas Virais de Fusão/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Cápsulas Bacterianas/administração & dosagem , Dengue/virologia , Vírus da Dengue/genética , Feminino , Humanos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Neisseria meningitidis/classificação , Neisseria meningitidis/genética , Proteínas Virais de Fusão/administração & dosagem , Proteínas Virais de Fusão/genéticaRESUMO
Haemophilus influenzae type b vaccine was introduced into the Immunization Program of Brazil in 1999 and no study has evaluated the impact of Hib vaccination in H. influenzae carriage so far. In June 2010, Brazil introduced the 10-valent pneumococcal nontypeable H. influenzae (NTHi) conjugate vaccine (PHiD-CV). We investigated the prevalence of encapsulated H. influenzae and NTHi isolates in nasopharyngeal samples of 1192 children attending day-care centers in Goiânia, central Brazil. H. influenzae carriage rate was 32.1% and 38.4% of them carried ß-lactamase TEM-1 gene. Serotype f (4.6%) was the most frequent encapsulated isolate, type b was recovered in only 0.7% and carriage rate of NTHi was 23.3%. Recurrent acute otitis media and NTHi were independently associated with colonization by ß-lactamase producing H. influenzae. Changes in frequency of H. influenzae carriage isolates should be carefully monitored to assess the impact of the PHiD-CV on NTHi carriage in young children.
Assuntos
Cápsulas Bacterianas/administração & dosagem , Portador Sadio/epidemiologia , Infecções por Haemophilus/epidemiologia , Vacinas Anti-Haemophilus/administração & dosagem , Haemophilus influenzae/isolamento & purificação , Brasil/epidemiologia , Creches , Pré-Escolar , Feminino , Haemophilus influenzae/genética , Humanos , Lactente , Masculino , Nasofaringe/microbiologia , Otite Média/epidemiologia , Otite Média/microbiologia , Prevalência , beta-Lactamases/genéticaRESUMO
The introduction of type b Haemophilus influenzae (Hi b) conjugate vaccines for children as part of immunization schedules has led to a sharp drop in the incidence of Hi b disease. In 1999, the Haemophilus influenzae b DTwP-HB/Hi b vaccine was introduced into the primary immunization program in Mexico. There have been no studies evaluating the vaccine after the widespread immunization in our country. The immune response to Hi b vaccines in different countries varies both quantitatively and qualitatively. Replacement of Hi b strains is expected between pre- and post-vaccination eras. Documentation on these three aspects will be useful for decisions regarding the use of the vaccine. In this review, we show and discuss the potential benefits of vaccination with DTwP-HB/Hi b in Mexico in terms of our collected data obtained during the last 8 years on population genotype variations and on concentration and avidity of IgG antibodies. As the epidemiological follow-up data are missing, the evaluation of the results of these three types of studies, as a whole, allows clarification of the scenario of the protection after vaccination in Mexico, in absence of the drop in cases reports. These results reinforce the findings of postvaccination studies done elsewhere.
Assuntos
Cápsulas Bacterianas/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacinas Anti-Haemophilus/administração & dosagem , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/prevenção & controle , Humanos , México/epidemiologiaRESUMO
The development of new immune potentiators for human vaccines is an important and expanding field of research. In the present study, the ability of the capsular polysaccharide from Neisseria meningitidis serogroup A (CPS-A), a mannose-containing carbohydrate, to enhance the antibody production against a co-administered model vaccine antigen, is examined. A protein-meningococcal serogroup C capsular polysaccharide (CPS-C) conjugate was selected as the model antigen for this study. After subcutaneous immunization of Balb/C mice, the conjugate mixed with CPS-A induced higher anti-CPS-C IgG and IgG(2a) antibody levels and higher anti-meningococcal serogroup C bactericidal titers than the conjugate alone or mixed with CPS-C. The immuno-stimulatory properties exhibited by CPS-A and the fact that vaccines based on purified CPS-A has been safely used during decades to fight the serogroup A meningococcal disease, support the proposal to use CPS-A as immune potentiator for human vaccination studies.
Assuntos
Adjuvantes Imunológicos/isolamento & purificação , Anticorpos Antibacterianos/imunologia , Cápsulas Bacterianas/imunologia , Cápsulas Bacterianas/isolamento & purificação , Neisseria meningitidis Sorogrupo A/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antibacterianos/sangue , Cápsulas Bacterianas/administração & dosagem , Atividade Bactericida do Sangue , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Meningite Meningocócica/imunologia , Meningite Meningocócica/microbiologia , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Neisseria meningitidis Sorogrupo A/química , Polissacarídeos Bacterianos/administração & dosagem , Polissacarídeos Bacterianos/imunologia , Distribuição AleatóriaRESUMO
BACKGROUND: Haemophilus influenzae type b (Hib) conjugate vaccine reduces the risk of pneumonia in infants. OBJECTIVE: To determine the effect of Hib conjugate vaccine (HibCV) on the prevention of pneumonia as a complication among infants hospitalized for bronchiolitis. METHODS: This record-based case-control study was conducted at The Children's Hospital "Dr. Ovidio Aliaga U" in La Paz, Bolivia during 2003 and 2004. Cases were infants hospitalized for bronchiolitis under 1 year of age who developed radiological pneumonia during hospitalization. Controls were patients who had good clinical progress without the use of antibiotics. Pneumonia was defined by alveolar consolidation on chest X-ray that justified the use of antibiotics. RESULTS: Eighty patients were studied (16 cases and 64 controls). Their median age was 4.5 months. Demographic and clinical features were similar in both groups, except for a higher proportion of vomiting (56.3% vs. 28.1%; p<0.05) in the case group. The percentage of unvaccinated infants was significantly higher in cases (68.8% vs. 26.6%; p<0.05) and the length of hospital stay longer (8.5+/-5.4 vs. 3.1+/-2.2 days; p<0.05). There was a strong association between unvaccinated infants and the occurrence of pneumonia as a complication (odds ratio 6.1, 95% confidence interval 1.8-20.1; p<0.01). CONCLUSIONS: Unvaccinated infants admitted for bronchiolitis have a higher risk of radiologically confirmed pneumonia. Larger studies are needed to validate these results and reconsider the burden of Hib infection among infants in less developed countries.
Assuntos
Cápsulas Bacterianas/administração & dosagem , Bronquiolite/complicações , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/administração & dosagem , Pneumonia Bacteriana/prevenção & controle , Vacinação , Bolívia/epidemiologia , Estudos de Casos e Controles , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Feminino , Infecções por Haemophilus/complicações , Infecções por Haemophilus/epidemiologia , Vacinas contra Hepatite B/administração & dosagem , Hospitalização , Humanos , Lactente , Masculino , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/epidemiologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Estudos Retrospectivos , Vacinas Combinadas/administração & dosagem , Vacinas Conjugadas/administração & dosagemRESUMO
We evaluated the immunogenicity and safety of an investigational combination of 9-valent pneumococcal conjugate vaccine (PCV9) and meningococcal group C conjugate (MnCC) vaccine (PCV9-MnCC) administered concomitantly with Haemophilus influenzae type b (Hib) conjugate vaccine, and of a combination of the three vaccines mixed together as a single injection (Hib-PCV9-MnCC), and compared them to separately administered PCV9 and MnCC dispensed to Chilean infants at 2, 4, and 6 months of age. The frequency of adverse events was similar among groups. Recipients of PCV9 alone or in combination with the other vaccines mounted significant antibody responses to the nine pneumococcal serotypes in PCV9, with >88% achieving protective levels of > or =0.35microg/mL. For serotypes 6B, 9V, and 5, recipients of PCV9 alone had significantly higher geometric mean concentrations (GMCs) than those of the other vaccine groups. Similarly, the GMC of anti-PRP antibodies was significantly lower among recipients of Hib-PCV9-MnCC than among those who received Hib vaccine separately from PCV9 or MnCC. In Chilean infants, PCV9, PCV9-MnCC, and Hib-PCV9-MnCC were highly immunogenic and safe. Overall, interactions of PCV9, MnCC and Hib affected the magnitude (GMC) of the primary antibody responses to some of the antigens, but not the percentage of subjects who achieved protective antibody thresholds.
Assuntos
Cápsulas Bacterianas/administração & dosagem , Proteínas de Bactérias/imunologia , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Meningocócicas/administração & dosagem , Vacinas Pneumocócicas/administração & dosagem , Vacinas Combinadas , Anticorpos Antibacterianos/sangue , Cápsulas Bacterianas/efeitos adversos , Cápsulas Bacterianas/imunologia , Chile , Vacinas Anti-Haemophilus/efeitos adversos , Vacinas Anti-Haemophilus/imunologia , Haemophilus influenzae/imunologia , Humanos , Lactente , Vacinas Meningocócicas/efeitos adversos , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Vacinas Pneumocócicas/efeitos adversos , Vacinas Pneumocócicas/imunologia , Método Simples-Cego , Streptococcus pneumoniae/imunologia , Vacinação , Vacinas ConjugadasRESUMO
OBJECTIVES: Widespread use of Haemophilus influenzae type b (Hib) vaccines has dramatically reduced the burden of Hib disease throughout the Americas. Few studies have evaluated the impact of Hib vaccination on non-culture-confirmed disease. This study analyzed trends in probable bacterial meningitis before and after the introduction of Hib vaccine in the Dominican Republic and estimated vaccine effectiveness against Hib meningitis. METHODS: Meningitis cases among children < 5 years of age were identified from admission records of the main pediatric hospital in Santo Domingo during 1998-2004. Laboratory criteria were used to classify meningitis cases with probable bacterial etiology; confirmed cases had positive bacterial culture or antigen detection in cerebrospinal fluid. Cumulative incidence rates of confirmed and probable bacterial meningitis were calculated for children living in the National District. Confirmed cases of Hib meningitis were enrolled in a case-control study with age- and neighborhood-matched control children to calculate vaccine effectiveness. RESULTS: Before vaccine introduction, annual rates of meningitis with probable bacterial etiology were 49 cases per 100 000 children < 5 years old; Hib accounted for 60 percent of confirmed bacterial cases. During 2002-2004, after vaccine introduction, annual rates of probable bacterial meningitis were 65 percent lower at 16 cases per 100 000, and Hib accounted for 26 percent of confirmed cases. Rates of Hib meningitis and probable bacterial meningitis with no determined etiology declined by 13 and 17 cases per 100 000, respectively. CONCLUSIONS: Introduction of Hib vaccine substantially reduced the incidence of confirmed and probable bacterial meningitis in the Dominican Republic. The estimated impact of Hib vaccination was twice as great when non-culture-confirmed disease was included.
OBJETIVOS: El uso generalizado de la vacuna contra Haemophilus influenzae tipo b (Hib) ha permitido reducir radicalmente la carga de enfermedad por Hib en las Américas. Pocos estudios han evaluado el impacto de la vacunación contra Hib sobre los casos no confirmados mediante cultivo. En este estudio se analizaron las tendencias en el número de casos probables de meningitis bacteriana antes y después de la introducción de la vacuna contra Hib en la República Dominicana y se estimó la eficacia de la vacuna contra la meningitis. MÉTODOS: Se identificaron los casos de meningitis en niños menores de 5 años a partir de los registros de ingreso del principal hospital pediátrico de Santo Domingo entre 1998 y 2004. Los casos de meningitis con probable etiología bacteriana se clasificaron según criterios de laboratorio; los casos confirmados contaban con cultivo bacteriano positivo o detección de antígenos específicos en el líquido cefalorraquídeo. Se calcularon las tasas de incidencia acumulada de casos confirmados y probables de meningitis en los niños que vivían en el Distrito Nacional. Los casos confirmados de meningitis por Hib se incorporaron a un estudio de casos y controles -pareados según la edad y el barrio de residencia- para calcular la eficacia de la vacuna. RESULTADOS: Antes de la introducción de la vacuna, la tasa anual de meningitis de posible etiología bacteriana era de 49 casos por 100 000 niños menores de 5 años; de los casos confirmados de origen bacteriano, 60 por ciento fue por Hib. En el período 2002-2004, después de la introducción de la vacuna, la tasa anual de meningitis de posible etiología bacteriana fue de 16 casos por 100 000, es decir 65 por ciento más baja, y 26 por ciento de los casos confirmados correspondieron a Hib. Las tasas de meningitis por Hib y de posible origen bacteriano de etiología desconocida se redujeron en 13 y 17 casos por 100 000, respectivamente. CONCLUSIONES: La introducción de la vacuna contra Hib redujo sustancialmente la incidencia de casos de meningitis confirmados y probables en la República Dominicana. El impacto estimado de la vacunación contra Hib fue dos veces mayor cuando se consideraron los casos no confirmados mediante cultivo.
Assuntos
Humanos , Pré-Escolar , Criança , Cápsulas Bacterianas/administração & dosagem , Vacinas Anti-Haemophilus/administração & dosagem , Haemophilus influenzae tipo b/isolamento & purificação , Meningite por Haemophilus/epidemiologia , Meningite por Haemophilus/microbiologia , República Dominicana/epidemiologiaRESUMO
This study evaluated the vaccination response to Haemophilus influenzae type b (Hib) in malnourished pregnant women (MN), cord blood (CB) and in infants at two and six months of age for comparison with a control group (C). Twenty-eight malnourished pregnant women and 29 pregnant controls were immunized with conjugated Act-HIB(R) in the third trimester of pregnancy. Blood samples were collected from all before the immunization, during labor (post immunization), and from CB. All infants were immunized with Hib vaccine according to normal vaccine schedule and sera were collected at two and six months of age. Antibody levels to polyribosylribitol phosphate (PRP) were similar for both groups. Preimmunization: MN 1.94 microg/mL, C 1.68 microg/mL; post-vaccination: MN 18.53 microg/mL and C 17.55 microg/mL; in CB from MN 14.46 microg/mL and from C 17.04 microg/mL. Infants from MN and C mothers presented respectively at two months: 5.18 microg/mL and 8.60 microg/mL and at six months: MN 3.42 microg/mL and C 2.18 microg/mL. Antibody levels were similar in both groups studied (p = 0.485), however the vertical transmission rate was 14% lower in the MN pregnant group. Levels of antibodies > 0.15 microg/mL were found in all newborns from the MN pregnant group. Pregnant MN presented an immunological response to Hib vaccine similar to group C, however, vertical transmission rate of antibodies to PRP in the MN pregnant group was 14% lower than that in C, suggesting a less efficient passage of antibodies within this group.
Assuntos
Anticorpos Antibacterianos/sangue , Infecções por Haemophilus/prevenção & controle , Haemophilus influenzae tipo b/imunologia , Desnutrição/imunologia , Troca Materno-Fetal/imunologia , Complicações na Gravidez/imunologia , Cápsulas Bacterianas/administração & dosagem , Cápsulas Bacterianas/imunologia , Estudos de Casos e Controles , Feminino , Sangue Fetal , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Recém-Nascido , Polissacarídeos/imunologia , Gravidez , Resultado da Gravidez , Terceiro Trimestre da Gravidez , Fatores de TempoRESUMO
This study evaluated the vaccination response to Haemophilus influenzae type b (Hib) in malnourished pregnant women (MN), cord blood (CB) and in infants at two and six months of age for comparison with a control group (C). Twenty-eight malnourished pregnant women and 29 pregnant controls were immunized with conjugated Act-HIB® in the third trimester of pregnancy. Blood samples were collected from all before the immunization, during labor (post immunization), and from CB. All infants were immunized with Hib vaccine according to normal vaccine schedule and sera were collected at two and six months of age. Antibody levels to polyribosylribitol phosphate (PRP) were similar for both groups. Preimmunization: MN 1.94 µg/mL, C 1.68 µg/mL; post-vaccination: MN 18.53 µg/mL and C 17.55 µg/mL; in CB from MN 14.46 µg/mL and from C 17.04 µg/mL. Infants from MN and C mothers presented respectively at two months: 5.18 µg/mL and 8.60 µg/mL and at six months: MN 3.42 µg/mL and C 2.18 µg/mL. Antibody levels were similar in both groups studied (p = 0.485), however the vertical transmission rate was 14 percent lower in the MN pregnant group. Levels of antibodies > 0.15 µg/mL were found in all newborns from the MN pregnant group. Pregnant MN presented an immunological response to Hib vaccine similar to group C, however, vertical transmission rate of antibodies to PRP in the MN pregnant group was 14 percent lower than that in C, suggesting a less efficient passage of antibodies within this group.
Assuntos
Feminino , Humanos , Recém-Nascido , Gravidez , Anticorpos Antibacterianos/sangue , Infecções por Haemophilus/prevenção & controle , Haemophilus influenzae tipo b/imunologia , Desnutrição/imunologia , Troca Materno-Fetal/imunologia , Complicações na Gravidez/imunologia , Cápsulas Bacterianas/administração & dosagem , Cápsulas Bacterianas/imunologia , Estudos de Casos e Controles , Sangue Fetal , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Resultado da Gravidez , Terceiro Trimestre da Gravidez , Polissacarídeos/imunologia , Fatores de TempoRESUMO
OBJECTIVES: Widespread use of Haemophilus influenzae type b (Hib) vaccines has dramatically reduced the burden of Hib disease throughout the Americas. Few studies have evaluated the impact of Hib vaccination on non-culture-confirmed disease. This study analyzed trends in probable bacterial meningitis before and after the introduction of Hib vaccine in the Dominican Republic and estimated vaccine effectiveness against Hib meningitis. METHODS: Meningitis cases among children < 5 years of age were identified from admission records of the main pediatric hospital in Santo Domingo during 1998-2004. Laboratory criteria were used to classify meningitis cases with probable bacterial etiology; confirmed cases had positive bacterial culture or antigen detection in cerebrospinal fluid. Cumulative incidence rates of confirmed and probable bacterial meningitis were calculated for children living in the National District. Confirmed cases of Hib meningitis were enrolled in a case-control study with age- and neighborhood-matched control children to calculate vaccine effectiveness. RESULTS: Before vaccine introduction, annual rates of meningitis with probable bacterial etiology were 49 cases per 100 000 children < 5 years old; Hib accounted for 60% of confirmed bacterial cases. During 2002-2004, after vaccine introduction, annual rates of probable bacterial meningitis were 65% lower at 16 cases per 100 000, and Hib accounted for 26% of confirmed cases. Rates of Hib meningitis and probable bacterial meningitis with no determined etiology declined by 13 and 17 cases per 100 000, respectively. CONCLUSIONS: Introduction of Hib vaccine substantially reduced the incidence of confirmed and probable bacterial meningitis in the Dominican Republic. The estimated impact of Hib vaccination was twice as great when non-culture-confirmed disease was included.