Lower peripheral blood CD14+ monocyte frequency and higher CD34+ progenitor cell frequency are associated with HBV vaccine induced response in HIV infected individuals

Abstract

We evaluated immunologic predictors of response to HBV vaccine administered in the presence or absence of GM-CSF in HIV infected individuals. We measured peripheral blood hematopoietic progenitor, monocyte and myeloid-derived suppressor cell (MDSC) frequencies, and expression of GMCSF receptor on monocytes and MDSCs, at baseline and 4weeks after immunization in relation to antibody response. We observed higher baseline progenitor and lower monocyte frequencies among week 16 antibody responders. Week 4 decline in MDSC frequency was associated with week 16 antibody response, while administration of GM-CSF was associated with preservation of these cells. No significant differences in GM-CSF receptor expression were observed in the presence vs. absence of GM-CSF. These findings are consistent with a positive role of progenitor cells and a potential negative role of monocytes in vaccine response. Additionally, GM-CSF augmented the preservation of peripheral blood MDSC, which may contribute to the lack of improved vaccine responses.

Trial registration: ClinicalTrials.gov NCT00272493.

Figure 1. Flow Cytometry gating scheme

Live cells were identified by viability stain and forward and side scatter. Hematopoietic progenitor cells were identified as CD34+. Monocytes were identified as CD14+. Myeloid lineage suppressor cells were identified as CD14+HLADR-CD11b+, CD34+CD14-HLADR-CD11b+, and CD34+CD14-HLADR-. GMCSF receptor (CD116) was measured on CD14+ and CD14+HLA DR-CD11b+ cells.

Figure 2. Baseline CD34+ progenitor and monocyte frequencies are associated with week 16 vaccine response

Baseline peripheral blood CD34+ progenitor (Panel A) and CD14+ monocyte (Panel C) frequency were measured by flow cytometric analysis. Correlation between CD34+ progenitor (Panel B) and monocyte (Panel D) frequency and week 16 hepatitis B surface antibody titer are shown. The horizontal lines on Panels A and C represent medians, and p-values are for the comparisons of responders and non-responders, regardless of study arm. P-values on Panels B and D are for the Spearman correlation coefficients.

Figure 3. GMCSF administration is associated with preservation of CD34+ CD14-HLADR-and CD34+ CD14-HLADR- CD11b+ cells

Baseline and week 4 peripheral blood frequencies of CD34+ CD14-HLADR- (panel A) and CD34+ CD14-HLADR- CD11b+ (panel B) cells are shown. GM-CSF receptor (CD116) expression as represented by mean fluorescent intensity (MFI) on monocytes comparing baseline and week 4 for each vaccine arm (panel C). P-values shown are for the change between baseline and week 4 within vaccine only arm. The size of the dot and the thickness of the lines are proportional to the number of subjects.