RESUMO
Endemic transmission of measles has been reestablished in Venezuela, and outbreaks of diphtheria remain ongoing across Latin America (LA). Hence, a large cross-sectional population-based serosurveillance study was conducted on Bonaire, one of the Dutch Leeward Antilles, to assess specific age and population groups at risk. Participants (aged 0-90 years) donated a blood sample and completed a questionnaire (n = 1,129). Antibodies against measles and diphtheria were tested using bead-based multiplex immunoassays. Our data revealed that immunity against measles is suboptimal, especially for those aged less than 5 years from Suriname, Aruba, and former Dutch Antilles (SADA), and adolescents from LA; and against diphtheria for persons aged more than 30 years, particularly among females and residents from SADA and LA. As refugees arrive persistently, health authorities on the Dutch Leeward Antilles should be on alert to detect early cases and prevent subsequent transmission. Ultimately, there is an urgent need for serosurveillance studies in the Caribbean region.
Assuntos
Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Difteria/epidemiologia , Difteria/transmissão , Sarampo/epidemiologia , Sarampo/transmissão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Países Baixos Caribenhos/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Difteria/prevenção & controle , Toxoide Diftérico/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Sarampo/prevenção & controle , Vacina contra Sarampo/imunologia , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Inquéritos e Questionários , Adulto JovemRESUMO
Finlay Vaccine Institute is developing a new heptavalent conjugate vaccine against Streptococcus pneumoniae. As infants are the target population, PCV7-TT will be necessarily co-administered with other vaccines, and then, the interactions represent a concern. The aim of this work is to evaluate the possible immunological interferences in rabbits as animal experimental model. Rabbits were immunized with Heberpenta®-L, VA-MENGOC-BC®, and PCV7-TT. Blood samples were taken fourteen days after final immunization for obtaining sera. Antibody responses to all antigens were evaluated by indirect ELISA. Functional responses against diphtheria and tetanus toxoid were done by in vivo seroneutralization assay. No interference was observed by PCV7-TT over the humoral response against diphtheria toxoid and meningococcal antigens (p > 0.05). A nonstatistically significant reduction (p > 0.05) was observed in the case of the humoral response against Haemophilus influenzae type b oligosaccharide. Concomitant administration of Heberpenta®-L and PCV7-TT increased twice the antibody titers as well as the protective activity against tetanus toxoid, but no statistical differences were found. The co-administration did not induce a reduction in the percent of responders against pneumococcal polysaccharides contained in PCV7-TT vaccine. Concomitant administration of PCV7-TT did not induce interferences over the evaluated antigens of Heberpenta®-L and VA-MENGOC-BC®. Also, no interference was observed on the immune response elicited by PCV7-TT. These preclinical results suggest that PCV7-TT will not result in a serious problem over the immune response elicited by the licensed vaccines Heberpenta®-L and VA-MENGOC-BC®. However, the clinical interference could be strictly studied during clinical trials in infants.
Assuntos
Anticorpos Antibacterianos/sangue , Vacina Pneumocócica Conjugada Heptavalente/imunologia , Imunidade Heteróloga , Infecções Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Animais , Antígenos de Bactérias/imunologia , Toxoide Diftérico/imunologia , Feminino , Vacinas Anti-Haemophilus/imunologia , Humanos , Lactente , Vacinas Meningocócicas/imunologia , Polissacarídeos Bacterianos/imunologia , Coelhos , Vacinação , Vacinas Virais/imunologiaRESUMO
Serogroup B Neisseria meningitidis (MenB) is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis) after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT) was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization). Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC® vaccine), its use should be restricted to outbreaks of meningococcal disease.
Assuntos
Anticorpos Antibacterianos/imunologia , Toxoide Diftérico/imunologia , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Infecções Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Animais , Formação de Anticorpos , Antígenos de Bactérias/imunologia , Feminino , Memória Imunológica , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Camundongos , Fatores de TempoRESUMO
Serogroup B Neisseria meningitidis (MenB) is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis) after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT) was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization). Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC® vaccine), its use should be restricted to outbreaks of meningococcal disease.
Assuntos
Animais , Feminino , Camundongos , Anticorpos Antibacterianos/imunologia , Toxoide Diftérico/imunologia , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Infecções Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Formação de Anticorpos , Antígenos de Bactérias/imunologia , Memória Imunológica , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Fatores de TempoRESUMO
Infections caused by Corynebacterium diphtheriae frequently induce situations in which very small doses of antigens injected intradermally can cause strong inflammatory reactions. This bacterium secretes the diphtheria toxin (DT), a virulence factor that can be lethal to the human organism at doses below 0.1 µg/kg of body weight. The present work proposes alternative methods of DT purification using affinity chromatography and of DT detoxification through conjugating with the polymer methoxypolyethylene glycol activated (mPEG). Tests were performed to evaluate: the formation of edemas and the presence of dermonecrotic activity, in vitro cytotoxicity to Vero cells, the neutralizing activity of serum from guinea pigs immunized with the diphtheria toxoid inactivated with mPEG, and the immunogenic activity of the purified and modified toxin. The results indicated that purification with Blue Sepharose was an efficient method, yielding antigen purity equivalent to 2600 Lf/mg of protein nitrogen. The modification of the Purified Toxin with mPEG did not result in the formation of edema or necrosis although it was immunogenic and stimulated the formation of antibodies that could neutralize the Purified Toxin. The toxoid obtained from the purified toxin maintained its immunogenic characteristics, inducing antibodies with neutralizing activity; edema and necrosis were still observed, however.
Assuntos
Cromatografia de Afinidade/métodos , Citotoxinas/isolamento & purificação , Toxina Diftérica/isolamento & purificação , Desintoxicação por Sorção/métodos , Animais , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Citotoxinas/química , Difteria/tratamento farmacológico , Difteria/metabolismo , Difteria/patologia , Toxina Diftérica/química , Toxoide Diftérico/imunologia , Toxoide Diftérico/farmacologia , Relação Dose-Resposta a Droga , Cobaias , Humanos , Testes de Neutralização , Polietilenoglicóis/química , Sefarose/análogos & derivados , Sefarose/química , Fatores de Tempo , Células VeroRESUMO
Chitosan (α-(1-4)-amino-2-deoxy-ß-D-glucan) is a deacetylated form of chitin, a polysaccharide from crustacean shells. Its unique characteristics, such as positive charge, biodegradability, biocompatibility, nontoxicity, and rigid structure, make this macromolecule ideal for an oral vaccine delivery system. We prepared reverse-phase evaporation vesicles (REVs) sandwiched by chitosan (Chi) and polyvinylic alcohol (PVA). However, in this method, there are still some problems to be circumvented related to protein stabilization. During the inverted micelle phase of protein nanoencapsulation, hydrophobic interfaces are expanded, leading to interfacial adsorption, followed by protein unfolding and aggregation. Here, spectroscopic and immunological techniques were used to ascertain the effects of the Hoffmeister series ions on diphtheria toxoid (Dtxd) stability during the inverted micelle phase. A correlation was established between the salts used in aqueous solutions and the changes in Dtxd solubility and conformation. Dtxd α-helical content was quite stable, which led us to conclude that encapsulation occurred without protein aggregation or without exposition of hydrophobic residues. Dtxd aggregation was 98% avoided by the kosmotropic, PO(2-)(4). This ion was used to prepare a stable Dtxd and immunologically recognized REV-Chi-PVA formulation in the presence of 50 mM of PO(2-)(4). Under these conditions, the Dtxd retained its immunological identity. Therefore, we could obtain the maximum Dtxd solubility and stability after contact with CH(3)CO(2)C(2)H(5) to begin its nanoencapsulation within ideal conditions. This was a technological breakthrough, because a simple solution, such as salt, addition avoided heterologous protein use.
Assuntos
Quitosana/química , Toxoide Diftérico/química , Composição de Medicamentos/métodos , Lipossomos/química , Conformação Molecular , Acetatos/química , Administração Oral , Adsorção , Animais , Toxoide Diftérico/imunologia , Toxoide Diftérico/metabolismo , Ensaio de Imunoadsorção Enzimática , Cavalos , Íons , Lipossomos/imunologia , Lipossomos/metabolismo , Micelas , Tamanho da Partícula , Fosfatos/química , Álcool de Polivinil/química , Estabilidade Proteica , Desdobramento de Proteína , Sais , Vacinas/química , Vacinas/imunologiaRESUMO
Since genome sequence data became available there has been a marked increase in number of protein antigens that have been suggested as prospective vaccine components against Neisseria meningitidis B (MenB). Few studies have addressed the mechanisms by which meningococcal vaccines generate and sustain immunological memory. The goal of this study was to compare the B-cell response (antibody-secreting cells [ASC], memory B cell and IgG) evoked by a MenB vaccine (VA-MENGOC-BC(®)) with the B-cell response to diphtheria toxoid (DT) induced by a successful vaccine (Diphtheria-Tetanus-Pertussis [DTP]). The results showed different kinetics of specific ASC response after the primary and booster immunisations. Concerning the specific ASC kinetics, MenB vaccine induced a strong primary response, but the recall response showed a limited power over time. In contrast, DTP primary ASC response was weaker than the booster responses. We observed an increase in the relative percent of memory B cells after 1, 2 and 3 doses of MenB vaccine (mean of 0.8%, 1.3% and 1.6%, respectively) but without statistical significance. Similar frequencies were detected after boosting given at 4 months (mean of 1.3%) or 6 months (mean of 0.9%) following the third dose. DT specific memory B cell response showed a slight lower magnitude after the primary immunisation schedule (mean of 1.2% after the third dose) compared with the MenB response. However, a stronger memory B cell response was induced by booster doses of DTP vaccine at 4 months (mean of 1.9%) or 6 months (mean of 1.9%). The kinetics of specific IgG induced by both vaccines was similar, suggesting that memory B cells were responsible for the strong antibody response seen after the booster vaccination.
Assuntos
Toxoide Diftérico/imunologia , Imunidade Humoral , Memória Imunológica , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo B/imunologia , Animais , Anticorpos Antibacterianos/sangue , Linfócitos B/imunologia , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Feminino , Imunização Secundária , Imunoglobulina G/sangue , Infecções Meningocócicas/imunologia , Infecções Meningocócicas/prevenção & controle , CamundongosRESUMO
In Brazil, until 2004, the immunization policy against diphtheria involved childhood vaccination with no official routine booster dose administered after 15 years of age. This study assessed functional antibody levels against diphtheria among blood donors. A total of 140 blood samples were collected, and diphtheria antitoxin levels were evaluated by Vero cell neutralization test. The mean age of the population was 34 years old (range: 18-61 years); 37.8% females and 62.2% males. Overall, 30.7% (95%, CI: 23.4-38.7) individuals presented neutralizing antitoxin antibody titers < 0.01 IU/ml; 42.1% (95%, CI: 34.1-50.4) showed values between 0.01-0.09 IU/ml and, 27.1% (95%, CI: 20.2-34.9) had (3) 0.1 IU/ml. In the subgroup of individuals with history of diphtheria immunization during childhood (85%), a number of 28.5% showed unprotective levels of circulating neutralizing antibody (< 0.01 IU/ml). Despite the continuous progress of immunization programs directed to Brazilian population, currently healthy adults remain susceptible to diphtheria.
Assuntos
Anticorpos Antibacterianos/sangue , Corynebacterium diphtheriae/imunologia , Toxoide Diftérico/sangue , Difteria/imunologia , Adolescente , Adulto , Animais , Anticorpos Antibacterianos/imunologia , Doadores de Sangue , Brasil , Chlorocebus aethiops , Difteria/prevenção & controle , Toxoide Diftérico/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Estudos Soroepidemiológicos , Vacinação , Células VeroRESUMO
In Brazil, until 2004, the immunization policy against diphtheria involved childhood vaccination with no official routine booster dose administered after 15 years of age. This study assessed functional antibody levels against diphtheria among blood donors. A total of 140 blood samples were collected, and diphtheria antitoxin levels were evaluated by Vero cell neutralization test. The mean age of the population was 34 years old (range: 18-61 years); 37.8 percent females and 62.2 percent males. Overall, 30.7 percent (95 percent, CI: 23.4-38.7) individuals presented neutralizing antitoxin antibody titers < 0.01 IU/ml; 42.1 percent (95 percent, CI: 34.1-50.4) showed values between 0.01-0.09 IU/ml and, 27.1 percent (95 percent, CI: 20.2-34.9) had ³ 0.1 IU/ml. In the subgroup of individuals with history of diphtheria immunization during childhood (85 percent), a number of 28.5 percent showed unprotective levels of circulating neutralizing antibody (< 0.01 IU/ml). Despite the continuous progress of immunization programs directed to Brazilian population, currently healthy adults remain susceptible to diphtheria.
Assuntos
Adolescente , Adulto , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Antibacterianos/sangue , Corynebacterium diphtheriae/imunologia , Toxoide Diftérico/sangue , Difteria/imunologia , Anticorpos Antibacterianos/imunologia , Doadores de Sangue , Brasil , Chlorocebus aethiops , Toxoide Diftérico/imunologia , Difteria/prevenção & controle , Testes de Neutralização , Estudos Soroepidemiológicos , Vacinação , Células VeroRESUMO
Immune responses to meningococcal conjugate (Menactra; MCV-4) and plain polysaccharide (Menomune-A/C/Y/W-135; PSV-4) vaccines against serogroups A, C, Y, and W-135 were assessed in 220 of 1037 Chilean children aged 2 to 10 years participating in a comparative safety trial. Both vaccines were generally well tolerated. Geometric mean serum bactericidal antibody (SBA) titers 28 days postvaccination were comparable in both groups for all four serogroups. Seroconversion was evident in > 97% of MCV-4 and > 90% of PSV-4 vaccinees who tested seronegative at baseline. Menactra safely induced broad and robust immune responses against serogroups A, C, Y and W-135 in this population.