Resposta de anticorpos opsonizantes em crianças e adolescentes infectados com HIV após vacinação contra Neisseria meningitidis sorogrupo C.

• Autor(a) principal: Alvino, Raquel Marinho
• 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/1/14448
• topic: Meningococcal disease; HIV; Opsonophagocytic activity; Meningococcal conjugate vaccine; Bactericidal antibodies; Doença meningocócica; HIV; Atividade opsonofagocitária; Vacina meningocócica conjugada; Anticorpos bactericidas; Doença meningocócica; CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA::MICROBIOLOGIA MEDICA

Serogroup C meningococcal disease is of great interest in public health, responsible for severe sequelae and mortality rates. Since 2006 the National Immunization Program from Brazilian Ministry of Healthy, has introduced the conjugate meningococcal serogroup C (MenC) vaccine for HIV+ children and adolescents. As a protective surrogate induced by anti-MenC vaccine bactericidal antibody titers greater than or equal to 1:4 are considered. Alternatively, opsonic antibodies have also been a subject of discussion as an important tool to analyze antibody response induced by meningococcal vaccines. The goal of this study was to evaluate the opsonic antibody response after primary immunization and the booster dose of a conjugate MenC vaccine (Novartis Vaccines, Siena, Italy administrated in 0.5 mL intramuscular injection) in HIV+ children and adolescents. Blood samples from 57 HIV+ children and adolescents (2-18 years of old) were collected before and after two doses of MenC vaccine. Twenty-nine HIV- subjects exposed to virus composed control group. Opsonic antibody assay was based on internalization of fluorescent beads adsorbed to C polysaccharide, and mediated by neutrophils, in the presence of human complement (1%). Results were analyzed by flow cytometry and associations between opsonic and bactericidal antibody response against two epidemic strains were also investigated. In order to evaluate the immunoglobulin (Ig) class responsible for effector response, 11 serum were selected to IgG depletion and analyzed by opsonic and bactericidal assays. Significant increase (P < 0,0001) were observed in opsonic antibody response between pre- and post-vaccination serum, with responders rates of 13,3% (before vaccination), 45% (after one dose), 5,3% (one year after one dose) and 57,9% (after the second dose, administered one year after first dose). There was no significant difference between responders subjects after one and two vaccine doses. For control group, the frequency of responders after single dose (41,4%) was similar to HIV+ group. Seroconversion frequencies of HIV+ patients after one and two doses were 23,3% and 38,6%, respectively. In control group it was observed 34,5% after one dose. There were positive and significant correlations (r = 0,43 to 0,69; P < 0,0001 to 0,0007) between opsonic and bactericidal antibody responses after one and two doses of vaccine. About 54,5% serum revealed IgG as bactericidal immunoglobulin, 9,1% indicated IgM and 36,4% revealed IgG or IgM. However, inconclusive results were detected by identification of Ig class as opsonin. Therefore, it was necessary two injections of MenC-CRM197 vaccine to induce a seroconversion frequency (opsonic antibodies) in HIV+ patients, similar to that observed after a single dose in HIV- subjects, suggesting a limitation of immune system in infected patients. Positive and significant correlations between opsonic and bactericidal antibodies suggest that opsonophagocytic activity is an important effector response induced by vaccination against MenC.