RESUMO
Vaccination against disease aims at the induction of long-lasting cellular and humoral immune responses. Few studies have addressed the mechanisms by which meningococcal vaccines generate and sustain immunological memory. The goal of this study was to investigate the development of long-term humoral and cellular memory to Neisseria meningitidis serogroup B (MenB) in health subjects after immunisation with the Cuban outer membrane protein (OMP) vaccine (VA-MENGOC-BC). The results showed that three doses of vaccine were necessary to induce a detectable memory B-cell response (mean of 0.46%) which became undetectable 6 months later. After boosting, only 2 of 5 individuals responded with an increase in memory B-cell frequencies (values of 0.15% and 0.34%). Bactericidal and opsonic antibody levels were higher after primary immunisation (log(2) mean and median of 4.7 and 1212, respectively) when compared with post-booster response (log(2) mean of 2.6 and median of 285, respectively). Together, these data suggest a failure of vaccine to induce long-term memory B-cell and serological memory in adults. However, we observed a significant and functional memory T-cell response specially after boosting, with a predominance of activated (CD69(+)) central memory T-cell (CD4(+)CD45(-)CCR7(+)) response. Therefore, this study suggests that vaccination with the MenB vaccine induced the generation and activation of memory T-cells but failed to maintain the memory B-cell population at a stable size and/or function.
Assuntos
Anticorpos Antibacterianos/biossíntese , Linfócitos B/imunologia , Imunização Secundária , Memória Imunológica , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo B/imunologia , Linfócitos T/imunologia , Adulto , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos T/análise , Proteínas da Membrana Bacteriana Externa/imunologia , Antígenos CD4/análise , Feminino , Humanos , Lectinas Tipo C/análise , Antígenos Comuns de Leucócito/análise , Masculino , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Pessoa de Meia-Idade , Receptores CCR7/análise , VacinaçãoRESUMO
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
There is no universal vaccine against serogroup B meningococcus (Men B). We investigated the development of spleen and bone marrow-specific IgG-secreting plasma cells (ASC) in mice immunised with the Cuban outer membrane protein (OMP) vaccine (VA-MENGOC-BC). Bone marrow was the predominant anatomical site of specific ASC and showed constant ASC levels (approximately 4%) at each time point analysed, indicating the production of long-lived ASC. A mean of 2.36 and 0.35% of Men B ASC was detected in spleen after the third dose and 2 months later, respectively, indicating a short-lived population. The data suggest that a short-lived ASC population in spleen was responsible for serum IgG anti-OMP while ASC from bone marrow produced persistent bactericidal antibodies against the vaccine strain. The response to the booster dose was consistent with development of memory B cells by primary vaccination.
Assuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Plasmócitos/imunologia , Animais , Formação de Anticorpos/imunologia , Atividade Bactericida do Sangue , Células da Medula Óssea/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Imunização , Imunização Secundária , Imunoglobulina G/biossíntese , Imunoglobulina G/imunologia , Camundongos , Baço/citologia , Baço/imunologiaRESUMO
The Paramirim aulacogen, hosted in the northern part of the São Francisco craton, corresponds to two superimposed and partially inverted rifts of Paleo and Neoproterozoic ages. The Rio Pardo salient of the Araçuaí belt defines the local limit of the craton and interferes with the aulacogen structures. In order to understand the mechanism and timing of the tectonic interaction between these tectonic features during the inversion processes, a structural analysis was undertaken in the southern Paramirim aulacogen and along the Rio Pardo salient. The results obtained indicate that the Rio Pardo salient formed during an early stage of closure of the Neoproterozoic Macaúbas rift system and consequent initiation of the Araçuaí orogen. The orogenic front propagated further northwards into the craton, causing a first stage of inversion in the southern terminus of the aulacogen trough. Subsequently, the Paramirim aulacogen experienced the main stage of inversion, which led to the development of a NNW-oriented basement involved fold-thrust system. These fabric elements overprint the Rio Pardo salient, and the structures of both the first and second stages of inversion affect the Salitre Formation, the youngestNeoproterozoic unit of the area, clearly indicating a Late Neoproterozoic maximum age for all the inversion stages of the Paramirim aulacogen.
RESUMO
The generation and maintenance of memory antibody response by different primary immunization schedules with the Cuban-produced outer membrane protein based vaccine was investigated in a murine model. We analyzed the duration of the antibody response (IgG-ELISA and bactericidal titer) and the effect of a booster dose on the antibody response. The IgG avidity index was determined in an attempt to find a marker for memory development. This study also included an analysis of IgG subclasses induced by primary and booster immunization. The specificity of bactericidal antibodies was investigated using local strains of the same serotype/serosubtype (4,7:P1.19,15) as the vaccine strain and mutant strains lacking major outer membrane proteins. A significant recall response was induced by a booster dose given 7 months after a primary series of 2, 3 or 4 doses of vaccine. The primary antibody response showed a positive dose-effect. In contrast, a negative dose-effect was found on the booster bactericidal antibody response. There was a significant increase in IgG1 levels after the fourth and booster doses. Three doses of vaccine were required to induce a significant increase in IgG avidity. Two injections of vaccine induced a significant antibody response to PorA protein, while 4 injections induced a larger range of specificities.