Células mieloides supressoras e monócitos na resposta à vacina contra o meningococo C em crianças e adolescentes infectados pelo HIV-1

Abstract

Meningococcal disease caused by Neisseria meningitidis serogroup C is responsible for outbreaks in Brazil, and studies indicate that its incidence is higher among children and adolescents with HIV. Protection induced by conjugated vaccine against MenC remains lower in this population than in HIV- individuals. Despite effective viral suppression with antiretroviral therapy (ART), a state of chronic immune activation and evidence of T-cell activation persists. Although it is established that the immune response to meningococcus is effective through the production of bactericidal antibodies, there are few studies on the behavior of innate immune cells during the vaccination process in this group of individuals. Myeloid-Derived Suppressor Cells (MDSCs) are a heterogeneous group of cells whose frequency has been correlated with increased viral load and reduced CD4 LT count in HIV+ patients.The objective of this study was to characterize the populations of MDSC and monocytes in children and adolescents (6 to 17 years old) infected or not with HIV-1 and immunized with the MenC-CRM197 conjugate vaccine. Blood samples were obtained before (V1) and after the first dose of the vaccine (V2), and before (V3) and after (V4) second dose. The interval between doses was eleven months, and the interval between V1 and V2, and V3 and V4, was two months. Peripheral blood mononuclear cells (PBMC) were obtained for the characterization of MDSC's and monocytes by flow cytometry and after were correlated with the viral load and vaccine-induced bactericidal antibody (SBA) titers. Two distinct MDSC subpopulations were observed, CD33hiCD11b+ and CD33lowCD11b+, and three subpopulations of monocytes; classical monocytes CD14+CD16- , intermediate monocytes CD14+CD16+, and non-classical monocytes CD14intCD16+. After the second dose (V4), we observed a significantly higher frequency (12.8%) (P = 0.038) of the CD33lowCD11b+ population among patients without ART compared to those under treatment (4.7%). There was an inverse and significant correlation between viral load and the frequency of the ratio obtained between CD4 T cells and MDSC CD33lowCD11b+ before (r=-0.65, P=0.048) and after the first dose of the vaccine (r=-0.68, P=0.038). A lower frequency of activated classical monocytes (CD163+) was observed in V4 (5%) when compared to V1 (15.9%) and V2 (12.7%) (P=0.010 and P=0.0047, respectively). The same trend was observed for the activated intermediate monocytes. Inverse and significant correlations were observed between the frequency of classic monocytes at V2 with baseline viral load at V1 (r=-0.65, P=0.048) and V2 (r=-0.66, P=0.043). The classic CD163+ monocytes after the 1st dose of the vaccine also exhibited an inverse and significant correlation with the viral load of both before (r= -0.84, P= 0.018) and after the 1st dose of the vaccine (r=-0.79, P=0.036). Negative correlations were observed between the frequency of MDSC CD33lowCD11b+ at V3 and the frequency of activated classic and intermediate monocytes after the booster dose of the vaccine (V4) (r=-0.071, P=0.057 and r=-0.83, P=0.015, respectively). The frequency of non-classical monocytes (CD14intCD16+) showed an inverse and significant correlation with the SBA titers obtained after the 1st dose of the vaccine (r=-0.70, P=0.022). These results indicate that the increase in MDSC frequency may be contributing to reduce monocyte activation and a possible association with improvement in the vaccine response