Abstract
Since 2006, meningococcal serogroup C (MenC) conjugate (MCC) vaccines have been supplied by the Brazilian government for HIV-infected children under 13 years old. For measuring protection against MenC, the serum bactericidal antibody (SBA) assay is the method of choice. The characterization of T follicular helper cells (TFH) cells has been an area of intensive study because of their significance in multiple human diseases and in vaccinology. The objective of this study was to characterize the phenotype of peripheral TFH cells and B cells and how they associated with each other and with SBA levels induced by vaccination as well as with serum cytokine levels of HIV-infected and non-infected children and adolescents. We found that CD27−IgD−CD21−CD38+ (exhausted B cells) as well as short-lived plasmablasts (CD27+IgD−CD21−CD38+) are increased in cART treated HIV patients and negatively associated with MCC vaccine induced SBA levels. Baseline frequency of activated peripheral TFH cells was a negative correlate for SBA response to MCC vaccine but positively correlated with circulating plasmablast frequency. Baseline IL4-levels positively associated with SBA response but showed a negative correlation with activated peripheral TFH cells frequency. The increased frequency of activated peripheral TFH cells found in non-responders to the vaccine implies that higher activation/differentiation of CD4 T cells within the lymph node is not necessarily associated with induction of vaccine responses.
Highlights
Meningococcal disease is a public health problem worldwide [1]
We have previously shown that only 30% of Brazilian HIVinfected children and adolescents seroconverted after one dose of meningococcal serogroup C conjugate (MCC) vaccine [5]
Regarding the CXCR3−CCR6+ peripheral T follicular helper cells (TFH) cells measured in HIV+ cohort, we found a significant inverse correlation between both activated (r = −0.756, p = 0.041) and resting (r = −0.829, p = 0.0167) phenotypes measured before the second dose of vaccine (V3) and serum bactericidal antibody (SBA) levels post-second vaccination (V4)
Summary
Meningococcal disease is a public health problem worldwide [1]. In Brazil, case fatality rates of this disease are as high as 18–20% of cases and serogroup C meningococcus (MenC) accounts for more than 80% of reported cases [2]. Since 2006, meningococcal serogroup C conjugate (MCC) vaccines have been supplied by the public sector for control of outbreaks and for high-risk patients, including HIV-infected children under 13 years old [3]. The immunization schedule consists of 3 injections of a MCC vaccine in the first year of life and a booster dose in adolescents aged 12–13 years [4]. We have previously shown that only 30% of Brazilian HIVinfected children and adolescents seroconverted (bactericidal antibody titers) after one dose of MCC vaccine [5]. Still 30% remained without protective antibody response after two doses of vaccine. Poor antibody response of vaccinees was associated with CD4 T cell activation identified through expression of CD38, HLA-DR and CCR5 [7]
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