Anticorpos neutralizantes da toxina diftérica em crianças e adolescentes HIV+ após imunização com uma vacina conjugada contra Neisseria meningitidis C

Abstract

Infection with the human immunodeficiency virus (HIV) represents a major public health problem. The immune response to routine vaccination of HIV+ children is lower than the response of healthy children. The Ministry of Health (MH) recommends routine vaccination of HIV+ children, except for live attenuated vaccines. Since 2006, the meningococcal C (MenC) conjugate vaccine is offered by the MH. The goal of this study was to evaluate the neutralizing antibody response to diphtheria toxin (Nab) in HIV+ patients after immunization with a conjugate vaccine against MenC (PS-C-CRM197, Novartis Vaccines). Blood samples from 42 children and adolescents (2-17 years) HIV+ in antiretroviral therapy (HAART) were collected before and after 1 and 2 doses of vaccine. The Nab response was assessed by neutralization assay (VERO cells). We analyzed the associations of Nab levels with: the number and percentage of CD4+ and CD4 nadir, the age, the MenC bactericidal antibody titles, the number of immunizations against diphtheria and the beginning of HAART. A significant increase was observed in Nab levels after the 1st dose (median of 0.31 IU/ml) of vaccine compared with pre-vaccination levels (median 0.01), followed by a significant drop after 1 year (median 0.03). The 2nd dose induced Nab (median 0.32) of similar titles to those detected after the 1st one. Only 19% of patients were protected against diphtheria (≥ 0.1 IU/ml Nab) prior vaccination. After the 1st and 2nd dose, 57% e 64,3%, respectively, of individuals were protected. Nab levels positively correlated before and after 1 (r = 0.71; P <0.0001) or 2 doses (r = 0.76; P <0.0001) of vaccine. We detected a positive correlation between the levels of Nab and the bactericidal antibody titles against MenC strain N79/96 (r = 0.36; P = 0.02) after the 1st dose, and against strains N79/96 and N753/00 (r = 0.65 for both; P <0.0001 and P <0.001, respectively) after the 2nd immunization. Positive associations were found between the levels of Nab after the 2nd dose and the absolute number of CD4+ (r = 0.34; P = 0.03). The percentage of CD4+ cells positively correlated with the Nab after 1 and 2 doses (r = 0.37; P = 0.02 for the 1st dose, r = 0.38 P = 0.01 for the 2nd dose). In conclusion, the PS-C-CRM197 vaccine induced Nab response in HIV+ patients. Due to the low rate of protected individuals before vaccination and the low adherence to the immunization program against diphtheria, it is important to figure out new strategies to improve vaccination coverage in HIV+ patients.