Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC®
Autor(a) principal: | |
---|---|
Data de Publicação: | 2011 |
Outros Autores: | |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UERJ |
Texto Completo: | http://www.bdtd.uerj.br/handle/1/17476 |
Resumo: | Neisseria meningitidis is one of the leading causes of bacterial meningitis and septicemia worldwide, particularly in children less than four years old. Currently, there is no universal vaccine against serogroup B meningococcus (MenB). Protective immunity against meningococcus is characterized by the presence and persistence of bactericidal antibody, but little is known about the mechanisms of development of the serological memory. In this study, we evaluated in animal model and in humans the generation and maintenance of antibody secreting cells (ASC) and memory B cell after vaccination against MenB. We used the diphtheria vaccine (dT or DTP) as a reference for efficacy in humans. Five to six-week old female Swiss mice in groups of 6 to 8 were immunized with three intramuscular injections of VA-MENGOC-BC® or DTP vaccine 2 weeks apart. Approximately 2, 4 or 6 months after the last dose, mice received a booster injection of the vaccine. Vaccination against MenB induced a higher ASC primary response compared with the booster response. In contrast, ASC response to dT was higher after booster than after primary immunization. Memory B-cell to MenB remained at constant levels (mean of 1%) during the whole study, but the response to diphtheria toxoid (TD) was higher after boosting (mean of 1.9%) when compared with the primary response. IgG, bactericidal and opsonic antibody concentrations to MenB was dose-dependent and was reactivated after booster doses. These data suggest that spleen memory B-cells were responsible for the strong boosting antibody response to MenB. For TD, both ASC and memory B-cell were important for maintenance of the serological memory. For the human study, six volunteers were immunized with three intramuscular injections of VA-MENGOC-BC® 6 to 8 weeks apart. Six months after the last dose, subjects received a booster dose. Another group of volunteers (n = 5) were immunized with a booster dose of dT vaccine. Three doses of vaccine were necessary to induce a detectable memory B-cell response against MenB in all individuals. However, these cells became undetectable 6 months later and for most of the individuals there was no reactivation of memory B-cells after boosting. The dT vaccine also induced a heterogeneous memory B-cell response but it was five-times higher than the response induced by VA-MENGOC-BC®. Functional antibodies induced by the MenB vaccine were of short duration with a small recall response. For both vaccines, the frequencies of central memory T-cells (TCM) and effector memory-T cells (TEM) have different profiles after primary vaccination and after booster. The recall response was characterized by increase in TCM and decrease in TEM. TCM was markedly more activated (CD69+) than TEM, especially after MenB vaccination. In conclusion, the data indicates that three doses of VA-MENGOC-BC® vaccine was of short effectiveness in humans and suggests that the low efficacy of the vaccine when used in the 90's in São Paulo and Rio de Janeiro, may be related to the deficiency in the generation and maintenance of specific memory B-cells |
id |
UERJ_18aca35c01c65bdd83573441af7cea1f |
---|---|
oai_identifier_str |
oai:www.bdtd.uerj.br:1/17476 |
network_acronym_str |
UERJ |
network_name_str |
Biblioteca Digital de Teses e Dissertações da UERJ |
repository_id_str |
2903 |
spelling |
Milagres, Lucimar GonçalvesAndrade, Arnaldo Feitosa Braga deHirata Junior, RaphaelSilveira, Ivna Alana Freitas Brasileiro daHofer, Cristina BarrosoBento, Cleonice Alves de MeloCruz, Simone da Costacbabdtd@gmail.com2022-04-05T14:27:48Z2011-07-08CRUZ, Simone da Costa. Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC®. 2011. 88 f. Tese (Doutorado em Microbiologia) - Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2011.http://www.bdtd.uerj.br/handle/1/17476Neisseria meningitidis is one of the leading causes of bacterial meningitis and septicemia worldwide, particularly in children less than four years old. Currently, there is no universal vaccine against serogroup B meningococcus (MenB). Protective immunity against meningococcus is characterized by the presence and persistence of bactericidal antibody, but little is known about the mechanisms of development of the serological memory. In this study, we evaluated in animal model and in humans the generation and maintenance of antibody secreting cells (ASC) and memory B cell after vaccination against MenB. We used the diphtheria vaccine (dT or DTP) as a reference for efficacy in humans. Five to six-week old female Swiss mice in groups of 6 to 8 were immunized with three intramuscular injections of VA-MENGOC-BC® or DTP vaccine 2 weeks apart. Approximately 2, 4 or 6 months after the last dose, mice received a booster injection of the vaccine. Vaccination against MenB induced a higher ASC primary response compared with the booster response. In contrast, ASC response to dT was higher after booster than after primary immunization. Memory B-cell to MenB remained at constant levels (mean of 1%) during the whole study, but the response to diphtheria toxoid (TD) was higher after boosting (mean of 1.9%) when compared with the primary response. IgG, bactericidal and opsonic antibody concentrations to MenB was dose-dependent and was reactivated after booster doses. These data suggest that spleen memory B-cells were responsible for the strong boosting antibody response to MenB. For TD, both ASC and memory B-cell were important for maintenance of the serological memory. For the human study, six volunteers were immunized with three intramuscular injections of VA-MENGOC-BC® 6 to 8 weeks apart. Six months after the last dose, subjects received a booster dose. Another group of volunteers (n = 5) were immunized with a booster dose of dT vaccine. Three doses of vaccine were necessary to induce a detectable memory B-cell response against MenB in all individuals. However, these cells became undetectable 6 months later and for most of the individuals there was no reactivation of memory B-cells after boosting. The dT vaccine also induced a heterogeneous memory B-cell response but it was five-times higher than the response induced by VA-MENGOC-BC®. Functional antibodies induced by the MenB vaccine were of short duration with a small recall response. For both vaccines, the frequencies of central memory T-cells (TCM) and effector memory-T cells (TEM) have different profiles after primary vaccination and after booster. The recall response was characterized by increase in TCM and decrease in TEM. TCM was markedly more activated (CD69+) than TEM, especially after MenB vaccination. In conclusion, the data indicates that three doses of VA-MENGOC-BC® vaccine was of short effectiveness in humans and suggests that the low efficacy of the vaccine when used in the 90's in São Paulo and Rio de Janeiro, may be related to the deficiency in the generation and maintenance of specific memory B-cellsNeisseria meningitidis é uma das principais causas de meningite bacteriana e septicemia em todo o mundo, acometendo principalmente crianças menores de 4 anos. Atualmente, não existe uma vacina universal contra o meningococo B (MenB). A imunidade protetora contra o meningococo caracteriza-se pela presença e persistência de anticorpos bactericidas, porém pouco se sabe sobre os mecanismos de desenvolvimento desta memória sorológica. Avaliamos em modelo animal e em humanos, a geração e manutenção das células secretoras de anticorpos (ASC) e dos linfócitos B de memória (LBm) após vacinação contra MenB. Utilizamos como referência a vacina diftérica (dT ou DTP), considerada ter ótima eficácia em humanos. Para o estudo em modelo animal, grupos de 6 a 8 camundongos suíços, fêmeas, de 5 a 6 semanas, foram imunizados com 3 doses da vacina VA-MENGOC-BC® ou DTP, via intramuscular, com intervalo de 2 semanas entre as doses. Aproximadamente 2, 4 ou 6 meses após a última dose, os animais receberam a dose reforço. A vacina anti-MenB induziu uma resposta primária de ASC maior que a resposta à dose reforço. Ao contrário, a resposta de ASC à vacina dT foi maior após o booster. A resposta de LBm anti-MenB permaneceu constante (média de 1%) ao longo de todo o estudo, mas a resposta ao toxóide diftérico (TD) foi maior após o booster (média de 1,9%) que após a imunização primária. A concentração de IgG, anticorpos bactericidas e opsonizantes contra MenB foi dose-dependente e foi reativada após a administração das doses reforços. Esses resultados sugerem que os LBm presentes no baço foram responsáveis pela forte resposta de anticorpos observada após a dose reforço. Para o TD, ambos ASC e LBm foram importantes na manutenção da memória sorológica. Para o estudo em humanos, seis voluntários foram imunizados com 3 doses da vacina VA-MENGOC-BC®, via intramuscular, com intervalo de 6 a 7 semanas entre as doses. Seis meses após a imunização primária, os indivíduos receberam uma dose reforço. Outro grupo de voluntários (n = 5) foi imunizado com uma dose reforço da vacina dT. Somente após a terceira dose da vacina anti-MenB foi possível detectar a presença de LBm em todos os indivíduos. Seis meses após a imunização primária, a frequência de LBm voltou ao seu nível basal e não foi reativada após a dose booster. A vacina dT também induziu uma resposta de LBm heterogênea, mas esta foi 5 vezes maior que a induzida por VA-MENGOC-BC®. A resposta de anticorpos funcionais anti-MenB foi de curta duração com pequena reativação após a dose reforço. As duas vacinas induziram diferentes frequências de LT de memória central (TCM) e de memória efetora (TEM) após a vacinação primária e após o booster. A resposta à dose booster foi caracterizada pelo aumento da população de linfócitos TCM e diminuição de TEM. A população de linfócitos TCM apresentou maior ativação (CD69+) que os linfócitos TEM, especialmente após a vacinação contra MenB. Concluindo, os dados desta tese indicam que a administração de 3 doses da vacina VA-MENGOC-BC® teve uma eficiência limitada em humanos e sugerem que a baixa eficácia da vacina, quando utilizada na década de 90 em São Paulo e no Rio de Janeiro, pode estar relacionada à deficiência na geração e manutenção de LBm específicosSubmitted by Thais Vieira NPROTEC (thaisvieira.uerj@gmail.com) on 2022-04-05T14:27:48Z No. of bitstreams: 1 Tese - Simone da Costa Cruz - 2011 - Completa.pdf: 5124464 bytes, checksum: 0b15e8b0d80fde6f9a74248ea29f1ffd (MD5)Made available in DSpace on 2022-04-05T14:27:48Z (GMT). No. of bitstreams: 1 Tese - Simone da Costa Cruz - 2011 - Completa.pdf: 5124464 bytes, checksum: 0b15e8b0d80fde6f9a74248ea29f1ffd (MD5) Previous issue date: 2011-07-08Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPqCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro - FAPERJapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em MicrobiologiaUERJBrasilCentro Biomédico::Faculdade de Ciências MédicasNeisseria meningitidisMeningiteVacinas meningocócicasEspecificidade de anticorposMemória imunológicaNeisseria meningitidis BBactericidal antibodyOpsonic antibodyImmunological memoryVaccineCIENCIAS BIOLOGICAS::IMUNOLOGIACIENCIAS BIOLOGICAS::IMUNOLOGIA::IMUNOLOGIA APLICADADesenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC®Development and maintenance of immunological memory after immunization against Neisseria meningitidis B with the VA-MENGOC-BC® vaccineinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALTese - Simone da Costa Cruz - 2011 - Completa.pdfTese - Simone da Costa Cruz - 2011 - Completa.pdfapplication/pdf5124464http://www.bdtd.uerj.br/bitstream/1/17476/2/Tese+-+Simone+da+Costa+Cruz+-+2011+-+Completa.pdf0b15e8b0d80fde6f9a74248ea29f1ffdMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82123http://www.bdtd.uerj.br/bitstream/1/17476/1/license.txte5502652da718045d7fcd832b79fca29MD511/174762022-04-05 11:27:48.348oai:www.bdtd.uerj.br:1/17476Tk9UQTogTElDRU7Dh0EgUkVERSBTSVJJVVMKRXN0YSBsaWNlbsOnYSBkZSBleGVtcGxvIMOpIGZvcm5lY2lkYSBhcGVuYXMgcGFyYSBmaW5zIGluZm9ybWF0aXZvcy4KCkxJQ0VOw4dBIERFIERJU1RSSUJVScOHw4NPIE7Dg08tRVhDTFVTSVZBCgpDb20gYSBhcHJlc2VudGHDp8OjbyBkZXN0YSBsaWNlbsOnYSwgdm9jw6ogKG8gYXV0b3IgKGVzKSBvdSBvIHRpdHVsYXIgZG9zIGRpcmVpdG9zIGRlIGF1dG9yKSBjb25jZWRlIMOgIFVuaXZlcnNpZGFkZSAKZG8gRXN0YWRvIGRvIFJpbyBkZSBKYW5laXJvIChVRVJKKSBvIGRpcmVpdG8gbsOjby1leGNsdXNpdm8gZGUgcmVwcm9kdXppciwgIHRyYWR1emlyIChjb25mb3JtZSBkZWZpbmlkbyBhYmFpeG8pLCBlL291IApkaXN0cmlidWlyIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyAoaW5jbHVpbmRvIG8gcmVzdW1vKSBwb3IgdG9kbyBvIG11bmRvIG5vIGZvcm1hdG8gaW1wcmVzc28gZSBlbGV0csO0bmljbyBlIAplbSBxdWFscXVlciBtZWlvLCBpbmNsdWluZG8gb3MgZm9ybWF0b3Mgw6F1ZGlvIG91IHbDrWRlby4KClZvY8OqIGNvbmNvcmRhIHF1ZSBhIFVFUkogcG9kZSwgc2VtIGFsdGVyYXIgbyBjb250ZcO6ZG8sIHRyYW5zcG9yIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyAKcGFyYSBxdWFscXVlciBtZWlvIG91IGZvcm1hdG8gcGFyYSBmaW5zIGRlIHByZXNlcnZhw6fDo28uCgpWb2PDqiB0YW1iw6ltIGNvbmNvcmRhIHF1ZSBhIFVFUkogcG9kZSBtYW50ZXIgbWFpcyBkZSB1bWEgY8OzcGlhIGEgc3VhIHRlc2Ugb3UgCmRpc3NlcnRhw6fDo28gcGFyYSBmaW5zIGRlIHNlZ3VyYW7Dp2EsIGJhY2stdXAgZSBwcmVzZXJ2YcOnw6NvLgoKVm9jw6ogZGVjbGFyYSBxdWUgYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIMOpIG9yaWdpbmFsIGUgcXVlIHZvY8OqIHRlbSBvIHBvZGVyIGRlIGNvbmNlZGVyIG9zIGRpcmVpdG9zIGNvbnRpZG9zIApuZXN0YSBsaWNlbsOnYS4gVm9jw6ogdGFtYsOpbSBkZWNsYXJhIHF1ZSBvIGRlcMOzc2l0byBkYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIG7Do28sIHF1ZSBzZWphIGRlIHNldSAKY29uaGVjaW1lbnRvLCBpbmZyaW5nZSBkaXJlaXRvcyBhdXRvcmFpcyBkZSBuaW5ndcOpbS4KCkNhc28gYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIGNvbnRlbmhhIG1hdGVyaWFsIHF1ZSB2b2PDqiBuw6NvIHBvc3N1aSBhIHRpdHVsYXJpZGFkZSBkb3MgZGlyZWl0b3MgYXV0b3JhaXMsIHZvY8OqIApkZWNsYXJhIHF1ZSBvYnRldmUgYSBwZXJtaXNzw6NvIGlycmVzdHJpdGEgZG8gZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIHBhcmEgY29uY2VkZXIgw6AgVUVSSiBvcyBkaXJlaXRvcyBhcHJlc2VudGFkb3MgbmVzdGEgbGljZW7Dp2EsIGUgcXVlIGVzc2UgbWF0ZXJpYWwgZGUgcHJvcHJpZWRhZGUgZGUgdGVyY2Vpcm9zIGVzdMOhIGNsYXJhbWVudGUgCmlkZW50aWZpY2FkbyBlIHJlY29uaGVjaWRvIG5vIHRleHRvIG91IG5vIGNvbnRlw7pkbyBkYSB0ZXNlIG91IGRpc3NlcnRhw6fDo28gb3JhIGRlcG9zaXRhZGEuCgpDQVNPIEEgVEVTRSBPVSBESVNTRVJUQcOHw4NPIE9SQSBERVBPU0lUQURBIFRFTkhBIFNJRE8gUkVTVUxUQURPIERFIFVNIFBBVFJPQ8ONTklPIE9VIApBUE9JTyBERSBVTUEgQUfDik5DSUEgREUgRk9NRU5UTyBPVSBPVVRSTyBPUkdBTklTTU8gUVVFIE7Dg08gU0VKQSBFU1RBClVOSVZFUlNJREFERSwgVk9Dw4ogREVDTEFSQSBRVUUgUkVTUEVJVE9VIFRPRE9TIEUgUVVBSVNRVUVSIERJUkVJVE9TIERFIFJFVklTw4NPIENPTU8gClRBTULDiU0gQVMgREVNQUlTIE9CUklHQcOHw5VFUyBFWElHSURBUyBQT1IgQ09OVFJBVE8gT1UgQUNPUkRPLgoKQSBVbml2ZXJzaWRhZGUgZG8gRXN0YWRvIGRvIFJpbyBkZSBKYW5laXJvIChVRVJKKSBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lIChzKSBvdSBvKHMpIG5vbWUocykgZG8ocykgCmRldGVudG9yKGVzKSBkb3MgZGlyZWl0b3MgYXV0b3JhaXMgZGEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvLCBlIG7Do28gZmFyw6EgcXVhbHF1ZXIgYWx0ZXJhw6fDo28sIGFsw6ltIGRhcXVlbGFzIApjb25jZWRpZGFzIHBvciBlc3RhIGxpY2Vuw6dhLgo=Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032022-04-05T14:27:48Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false |
dc.title.por.fl_str_mv |
Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC® |
dc.title.alternative.eng.fl_str_mv |
Development and maintenance of immunological memory after immunization against Neisseria meningitidis B with the VA-MENGOC-BC® vaccine |
title |
Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC® |
spellingShingle |
Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC® Cruz, Simone da Costa Neisseria meningitidis Meningite Vacinas meningocócicas Especificidade de anticorpos Memória imunológica Neisseria meningitidis B Bactericidal antibody Opsonic antibody Immunological memory Vaccine CIENCIAS BIOLOGICAS::IMUNOLOGIA CIENCIAS BIOLOGICAS::IMUNOLOGIA::IMUNOLOGIA APLICADA |
title_short |
Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC® |
title_full |
Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC® |
title_fullStr |
Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC® |
title_full_unstemmed |
Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC® |
title_sort |
Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC® |
author |
Cruz, Simone da Costa |
author_facet |
Cruz, Simone da Costa cbabdtd@gmail.com |
author_role |
author |
author2 |
cbabdtd@gmail.com |
author2_role |
author |
dc.contributor.advisor1.fl_str_mv |
Milagres, Lucimar Gonçalves |
dc.contributor.referee1.fl_str_mv |
Andrade, Arnaldo Feitosa Braga de |
dc.contributor.referee2.fl_str_mv |
Hirata Junior, Raphael |
dc.contributor.referee3.fl_str_mv |
Silveira, Ivna Alana Freitas Brasileiro da |
dc.contributor.referee4.fl_str_mv |
Hofer, Cristina Barroso |
dc.contributor.referee5.fl_str_mv |
Bento, Cleonice Alves de Melo |
dc.contributor.author.fl_str_mv |
Cruz, Simone da Costa cbabdtd@gmail.com |
contributor_str_mv |
Milagres, Lucimar Gonçalves Andrade, Arnaldo Feitosa Braga de Hirata Junior, Raphael Silveira, Ivna Alana Freitas Brasileiro da Hofer, Cristina Barroso Bento, Cleonice Alves de Melo |
dc.subject.por.fl_str_mv |
Neisseria meningitidis Meningite Vacinas meningocócicas Especificidade de anticorpos Memória imunológica |
topic |
Neisseria meningitidis Meningite Vacinas meningocócicas Especificidade de anticorpos Memória imunológica Neisseria meningitidis B Bactericidal antibody Opsonic antibody Immunological memory Vaccine CIENCIAS BIOLOGICAS::IMUNOLOGIA CIENCIAS BIOLOGICAS::IMUNOLOGIA::IMUNOLOGIA APLICADA |
dc.subject.eng.fl_str_mv |
Neisseria meningitidis B Bactericidal antibody Opsonic antibody Immunological memory Vaccine |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::IMUNOLOGIA CIENCIAS BIOLOGICAS::IMUNOLOGIA::IMUNOLOGIA APLICADA |
description |
Neisseria meningitidis is one of the leading causes of bacterial meningitis and septicemia worldwide, particularly in children less than four years old. Currently, there is no universal vaccine against serogroup B meningococcus (MenB). Protective immunity against meningococcus is characterized by the presence and persistence of bactericidal antibody, but little is known about the mechanisms of development of the serological memory. In this study, we evaluated in animal model and in humans the generation and maintenance of antibody secreting cells (ASC) and memory B cell after vaccination against MenB. We used the diphtheria vaccine (dT or DTP) as a reference for efficacy in humans. Five to six-week old female Swiss mice in groups of 6 to 8 were immunized with three intramuscular injections of VA-MENGOC-BC® or DTP vaccine 2 weeks apart. Approximately 2, 4 or 6 months after the last dose, mice received a booster injection of the vaccine. Vaccination against MenB induced a higher ASC primary response compared with the booster response. In contrast, ASC response to dT was higher after booster than after primary immunization. Memory B-cell to MenB remained at constant levels (mean of 1%) during the whole study, but the response to diphtheria toxoid (TD) was higher after boosting (mean of 1.9%) when compared with the primary response. IgG, bactericidal and opsonic antibody concentrations to MenB was dose-dependent and was reactivated after booster doses. These data suggest that spleen memory B-cells were responsible for the strong boosting antibody response to MenB. For TD, both ASC and memory B-cell were important for maintenance of the serological memory. For the human study, six volunteers were immunized with three intramuscular injections of VA-MENGOC-BC® 6 to 8 weeks apart. Six months after the last dose, subjects received a booster dose. Another group of volunteers (n = 5) were immunized with a booster dose of dT vaccine. Three doses of vaccine were necessary to induce a detectable memory B-cell response against MenB in all individuals. However, these cells became undetectable 6 months later and for most of the individuals there was no reactivation of memory B-cells after boosting. The dT vaccine also induced a heterogeneous memory B-cell response but it was five-times higher than the response induced by VA-MENGOC-BC®. Functional antibodies induced by the MenB vaccine were of short duration with a small recall response. For both vaccines, the frequencies of central memory T-cells (TCM) and effector memory-T cells (TEM) have different profiles after primary vaccination and after booster. The recall response was characterized by increase in TCM and decrease in TEM. TCM was markedly more activated (CD69+) than TEM, especially after MenB vaccination. In conclusion, the data indicates that three doses of VA-MENGOC-BC® vaccine was of short effectiveness in humans and suggests that the low efficacy of the vaccine when used in the 90's in São Paulo and Rio de Janeiro, may be related to the deficiency in the generation and maintenance of specific memory B-cells |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-07-08 |
dc.date.accessioned.fl_str_mv |
2022-04-05T14:27:48Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
CRUZ, Simone da Costa. Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC®. 2011. 88 f. Tese (Doutorado em Microbiologia) - Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2011. |
dc.identifier.uri.fl_str_mv |
http://www.bdtd.uerj.br/handle/1/17476 |
identifier_str_mv |
CRUZ, Simone da Costa. Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC®. 2011. 88 f. Tese (Doutorado em Microbiologia) - Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2011. |
url |
http://www.bdtd.uerj.br/handle/1/17476 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Microbiologia |
dc.publisher.initials.fl_str_mv |
UERJ |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Centro Biomédico::Faculdade de Ciências Médicas |
publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UERJ instname:Universidade do Estado do Rio de Janeiro (UERJ) instacron:UERJ |
instname_str |
Universidade do Estado do Rio de Janeiro (UERJ) |
instacron_str |
UERJ |
institution |
UERJ |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UERJ |
collection |
Biblioteca Digital de Teses e Dissertações da UERJ |
bitstream.url.fl_str_mv |
http://www.bdtd.uerj.br/bitstream/1/17476/2/Tese+-+Simone+da+Costa+Cruz+-+2011+-+Completa.pdf http://www.bdtd.uerj.br/bitstream/1/17476/1/license.txt |
bitstream.checksum.fl_str_mv |
0b15e8b0d80fde6f9a74248ea29f1ffd e5502652da718045d7fcd832b79fca29 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ) |
repository.mail.fl_str_mv |
bdtd.suporte@uerj.br |
_version_ |
1811728707716382720 |