Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC®

• Autor(a) principal: Cruz, Simone da Costa
• Data de Publicação: 2011
• Outros Autores: [e-mail]
• 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
• 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

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