Impacto da infecção pelo HIV na resposta imune de crianças e adolescentes após imunização com a vacina conjugada meningocócica contra o sorogrupo C

Abstract

Neisseria meningitidis serogroup C (MenC) has been the cause of outbreaks in Brazil since 2005. Vaccines conjugated against MenC are available in Brazil and are effective in immunologically normal patients, but little is known about the impact on HIV + patients. The main objective of this study was to analyze the response of neutralizing antibodies against diphtheria toxin induced by the conjugate vaccine, to investigate the influence of the expression of activation and inhibition markers on CD4 + T cells and to phenotypically characterize the circulating helper T cells (Tfh) and cells B and how these cells are associated with bactericidal antibody levels after immunization in HIV-infected children and adolescents responding to or not to the MenC conjugate vaccine (MCC). We report the association of anti-diphtheria neutralizing antibodies with bactericidal antibodies (SBA). Before vaccination, 50% HIV + patients had no protection against diphtheria and only 19% had complete protection. In HIV-infected individuals 56% had complete protection before immunization and 12% had no protection against diphtheria. After one and two immunizations, 96% of HIV- and 64% of HIV + showed complete protection against diphtheria. They indicate that CRM197 was able to induce a primary and / or reinforcement response in both groups of individuals. When assessing the expression of activation and inhibition markers, we observed that PD-1 and / or TIGIT expression was positively associated with CD4 + (HLA-DR + CD38 +) T cell activation and viral load but negatively correlated with response SBA in HIV + patients, as well as with the CD4-T cell count or percentage. Blood levels of IL-4 correlated positively with SBA titers, but negatively correlated with expression of the activation / inhibition markers. An opposite profile was observed for the chemokine CXCL-13. Suggesting that the expression of inhibitory and activation molecules may lead to poor response to the MCC vaccine in HIV + children and adolescents. By analyzing the phenotype of circulating Tfh cells and B cells we find that B cells depleted as well as short-lived plasmablast are increased in treated patients and negatively associated with MCC vaccine-induced SBA levels. The basal frequency of activated circulating Tfh cells correlated negatively with the SBA response but correlated positively with the frequency of circulating plasmablast cells. Baseline IL4 levels positively associated with the SBA response but showed a negative correlation with the frequency of activated circulating Tfh cells. Indicating that increased a frequency of circulating activated Tfh cells found in non-responders to the vaccine may imply that there is a greater activation / differentiation of CD4 + T cells within the lymph node.