RESUMEN
Currently, Neisseria meningitidis serogroup C (MenC) is the major cause of bacterial meningitis in Brazil, affecting mainly teenagers and adults due to the lack of routine public vaccination of these age groups. The goal of this study was to investigate the bactericidal antibody response and the development of CD4(+) T cell memory during the convalescent phase of patients infected with N. menigitidis. Most (85.7%) of the patients developed a protective antibody response against MenC and 57% also responded to N. meningitidis serogroup B. We detected a significant CD4(+) T central memory (TCM) response to meningococcal outer membrane proteins.
Asunto(s)
Formación de Anticuerpos , Linfocitos T CD4-Positivos/inmunología , Memoria Inmunológica , Infecciones Meningocócicas/inmunología , Adolescente , Adulto , Anticuerpos Antibacterianos/sangre , Proteínas de la Membrana Bacteriana Externa/inmunología , Brasil , Humanos , Persona de Mediana Edad , Neisseria meningitidis Serogrupo C/inmunología , Subgrupos de Linfocitos T/inmunología , Adulto JovenRESUMEN
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.
Asunto(s)
Anticuerpos Antibacterianos/biosíntesis , Linfocitos B/inmunología , Inmunización Secundaria , Memoria Inmunológica , Vacunas Meningococicas/inmunología , Neisseria meningitidis Serogrupo B/inmunología , Linfocitos T/inmunología , Adulto , Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/inmunología , Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Proteínas de la Membrana Bacteriana Externa/inmunología , Antígenos CD4/análisis , Femenino , Humanos , Lectinas Tipo C/análisis , Antígenos Comunes de Leucocito/análisis , Masculino , Infecciones Meningocócicas/prevención & control , Vacunas Meningococicas/administración & dosificación , Persona de Mediana Edad , Receptores CCR7/análisis , VacunaciónRESUMEN
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.