Avaliação da resposta imunológica após imunização de indivíduos adultos saudáveis com a vacina conjugada contra Neisseria meningitidis-CRM197 sorogrupo C: proliferação celular e produção de anticorpos funcionais

• Autor(a) principal: Lacerda, Aline Werneck
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/14446
• topic: Neisseria meningitidis; Meningococcal C conjugate vaccine; CRM197; Functional antibodies; Bactericidal antibodies; Neutralizing antibodies; Neisseria meningitidis; Meningite Conjugadas.; Vacinas Meningocócicas; Vacinas Conjugadas; Neisseria meningitidis; Vacina meningocócica conjugada; CRM197; Anticorpos funcionais; Anticorpo bactericida; Anticorpo neutralizante; CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA

Meningitis remains a serious public health problem causing from 50 thousand to 135 thousand deaths annually around the world. In Brazil, the main cause of this disease is Neisseria meningitidis serogroup C. The introduction of conjugate vaccines against this infection has made a new tool for prevention and control of epidemics. The effect of these vaccines is well elucidated, however, little is known about the immune response induced by their carriers. The purpose of this work was to evaluate the response of bactericidal antibodies induced by the vaccine anti-meningitis serogroup C conjugated to protein CRM197 (anti-MenC-CRM197) and the cross-protection against diphtheria inferred by the presence of the carries CRM197. Eight healthy adults volunteers had blood samples collected before and after 14 and 56 days of one or two doses of the vaccine anti-MenC-CRM197 for determination of bactericidal antibody to N753/00 strain of N. meningitidis using a source of human complement. The proliferative response of T CD4+ cells was performed by dilution of CFSE. Then, it was evaluated the cross-protection against diphtheria toxin analyzed through neutralisation assay with VERO cells. It was observed an increase in the concentration of bactericidal antibodies in 37.5% of the volunteers after the first dose and an even greater and significant increase (87.5 %) when introduced a second dose (p < 0.01). There was a slight increase in proliferative response of T CD4+ cells after the first dose, although not significant. We found a significant increase in neutralizing antibodies after first immunization, causing 100% of volunteers to achieve complete protection against diphtheria (titles higher than or equal to 0.1 IU/mL). After the second dose, we did not observe an increase in the concentration of neutralizing antibodies and the levels of protection remained stable. The correlations between the parameters measured were not significant, possibly due to the small sample number. These data presented showed the vaccine anti-MenC-CRM197 induced protection in a low percentage of volunteers (37.5 %) as well as the induction of bactericidal antibodies with a percentage of increase (87.5 %) after the second dose. There was a tendency to increase the proliferation of T CD4+ cells, but not significant. There was also an increase in the production of neutralizing antibodies anti-diphtheria toxin and this proved to be significant when related the periods before and after immunization (p < 0.01 for 14 and 56 days after the first dose and 14 days after booster, and p < 0.05 for 56 days after booster).