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1.
J Control Release ; 368: 184-198, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38395155

RESUMO

Streptococcus pneumoniae is an important human pathogen. Currently used conjugate vaccines are effective against invasive disease, but protection is restricted to serotypes included in the formulation, leading to serotype replacement. Furthermore, protection against non-invasive disease is reported to be considerably lower. The development of a serotype-independent vaccine is thus important and Pneumococcal surface protein A (PspA) is a promising vaccine candidate. PspA shows some diversity and can be classified in 6 clades and 3 families, with families 1 and 2 being the most frequent in clinical isolates. The ideal vaccine should thus induce protection against the two most common families of PspA. The aim of this work was to develop a liposome-based vaccine containing PspAs from family 1 and 2 and to characterize its immune response. Liposomes (LP) composed of dipalmitoylphosphatidylcholine (DPPC) and 3ß-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol) with or without α-galactosylceramide (α-GalCer) were produced by microfluidics, encapsulating PspA from clade 1 (PspA1, family 1) and/or clade 4 (PspA4Pro, family 2) followed by spray-drying with trehalose to form nanocomposite microparticles carriers (NCMP). LP/NCMPs showed good stability and preservation of protein activity. LP/NCMPs containing PspA1 and/or PspA4Pro were used for immunization of mice targeting the lungs. High serum IgG antibody titers against both PspA1 and PspA4Pro were detected in animals immunized with LP/NCMPs containing α-GalCer, with a balance of IgG1 and IgG2a titers. IgG in sera from immunized mice bound to pneumococcal strains from different serotypes and expressing different PspA clades, indicating broad recognition. Mucosal IgG and IgA were also detected. Importantly, immunization with LP/NCMPs induced full protection against strains expressing PspAs from family 1 and 2. Furthermore, CD4+ resident memory T cells were detected in the lungs of the immunized animals that survived the challenge.


Assuntos
Galactosilceramidas , Infecções Pneumocócicas , Streptococcus pneumoniae , Humanos , Animais , Camundongos , Lipossomos , Pós , Infecções Pneumocócicas/prevenção & controle , Proteínas de Bactérias , Imunização , Vacinas Pneumocócicas , Imunoglobulina G , Pulmão , Anticorpos Antibacterianos , Camundongos Endogâmicos BALB C
2.
J Control Release, v. 368, p. 184-198, abr. 2024
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5271

RESUMO

Streptococcus pneumoniae is an important human pathogen. Currently used conjugate vaccines are effective against invasive disease, but protection is restricted to serotypes included in the formulation, leading to serotype replacement. Furthermore, protection against non-invasive disease is reported to be considerably lower. The development of a serotype-independent vaccine is thus important and Pneumococcal surface protein A (PspA) is a promising vaccine candidate. PspA shows some diversity and can be classified in 6 clades and 3 families, with families 1 and 2 being the most frequent in clinical isolates. The ideal vaccine should thus induce protection against the two most common families of PspA. The aim of this work was to develop a liposome-based vaccine containing PspAs from family 1 and 2 and to characterize its immune response. Liposomes (LP) composed of dipalmitoylphosphatidylcholine (DPPC) and 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol) with or without α-galactosylceramide (α-GalCer) were produced by microfluidics, encapsulating PspA from clade 1 (PspA1, family 1) and/or clade 4 (PspA4Pro, family 2) followed by spray-drying with trehalose to form nanocomposite microparticles carriers (NCMP). LP/NCMPs showed good stability and preservation of protein activity. LP/NCMPs containing PspA1 and/or PspA4Pro were used for immunization of mice targeting the lungs. High serum IgG antibody titers against both PspA1 and PspA4Pro were detected in animals immunized with LP/NCMPs containing α-GalCer, with a balance of IgG1 and IgG2a titers. IgG in sera from immunized mice bound to pneumococcal strains from different serotypes and expressing different PspA clades, indicating broad recognition. Mucosal IgG and IgA were also detected. Importantly, immunization with LP/NCMPs induced full protection against strains expressing PspAs from family 1 and 2. Furthermore, CD4+ resident memory T cells were detected in the lungs of the immunized animals that survived the challenge.

3.
Rev Saude Publica ; 34(5): 499-505, 2000 Oct.
Artigo em Português | MEDLINE | ID: mdl-11105114

RESUMO

OBJECTIVE: To describe the lipid profile and the prevalence of hypercholesterolemia among schoolchildren aged 7 to 14 years in Campinas, São Paulo State, Brazil. METHODS: Plasma cholesterol levels, fractions, ratios and triglycerides were determined according to age and gender in a total of 1,600 schoolchildren. Hypercholesterolemia was considered borderline for 170 mg/dl/=200 mg/dl. RESULTS: Schoolchildren presented a cholesterol mean of 160 mg/dl, HDL-cholesterol mean of 49 mg/dl, LDL-cholesterol mean of 96 mg/dl, VLDL-cholesterol mean of 16 mg/dl, triglycerides mean of 79 mg/dl, cholesterol/HDL-cholesterol mean of 3.5 and LDL-cholesterol/HDL-cholesterol mean of 2.1. In general, females had higher cholesterol and triglycerides values than males. The prevalence of hypercholesterolemia was 35.0%: 15.6% was borderline high, 9.8% moderate and 9.5% severe. Females presented higher prevalence of hypercholesterolemia than males. CONCLUSIONS: The results pointed to the emergence of hypercholesterolemia as a public health problem in Brazil.


Assuntos
Hipercolesterolemia/epidemiologia , Lipídeos/sangue , Adolescente , Distribuição por Idade , Brasil/epidemiologia , Criança , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Hipercolesterolemia/etiologia , Masculino , Prevalência , Valores de Referência , Distribuição por Sexo , Triglicerídeos/sangue
4.
Cad Saude Publica ; 15(4): 871-81, 1999.
Artigo em Português | MEDLINE | ID: mdl-10633209

RESUMO

A quasi-experimental epidemiological study was performed to evaluate the effect of a nutritional supplement made from bovine blood on human blood parameters. Healthy women who were neither pregnant nor breast-feeding were allocated to two groups: study (n=32) and control (n=17). Women in the study group received 0.5 mg of iron per day, while controls received placebo. Food intake frequency and side effects related to ferrous sulfate were recorded. A 24-hour dietary recall was performed every two weeks, and blood samples were collected to determine biochemical parameters. Compared to controls, the study group showed higher serum iron and iron retention capacity, lower calorie, protein, and vitamin C intake, and lower consumption of dairy products and fruit. Adjusted mean blood parameters were calculated using ANOVA. The output showed increased serum iron (p=0.009) and decreased iron retention capacity (p=0.031) at the end of the study. The results favor use of the product to treat iron deficiency anemia.


Assuntos
Suplementos Nutricionais , Compostos Ferrosos/administração & dosagem , Hematínicos/administração & dosagem , Ferro/sangue , Adolescente , Adulto , Análise de Variância , Animais , Bovinos , Avaliação de Medicamentos , Índices de Eritrócitos , Comportamento Alimentar , Feminino , Ferritinas/sangue , Compostos Ferrosos/sangue , Hematínicos/sangue , Hematócrito , Hemoglobinometria , Humanos , Análise por Pareamento , Inquéritos Nutricionais , Método Simples-Cego
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