Abstract

Introduction: The Anthrax Vaccine Precipitated (AVP) is the UK licensed human anthrax vaccine which is given to individuals at risk of exposure to the pathogen. The vaccine is administered as a primary series of four vaccinations with an annual booster. The aim of this study was to investigate the effect of prior doses on the magnitude and quality of the recall response following re-immunisation with AVP. To measure quality we determined the Toxin neutralising activity of a sample subset (n = 28) and compared the responses seen using murine and human macrophage like cells. We also investigated the contribution of the host cell anthrax toxin receptors capillary morphogenesis gene 2 (CMG2), tumor endothelial marker 8 (TEM8), and integrin β1 (ITGB1) to the process [1]. Methods: The anthrax toxin specific antibody responses of 230 AVP immunised individuals were determined by ELISA. Toxin neutralisation activity was measured using murine J774a.1 macrophages [2] and PMA activated human THP1 macrophage like cells [3]. The distribution of the anthrax toxin receptors CMG2, TEM8 and ITGB1 on the surface of THP-1 cells was determined by FACS. Results: The mean IgG antibodies titers (µg/ml) for PA and LF were 138.79 (± 4.44) and 24.31 (± 0.7) while unexpectedly there was no detectable response to EF. Surprisingly we found no correlation between toxin neutralisation assay titers obtained using the murine and human cells. We did observe a marked difference in the expression of toxin receptors by differentiated (toxin sensitive) and undifferentiated (toxin resistant) human THP1 cells. Differentiation resulted in a reduction of CMG2 expression from 98 to 7.28% of cell expressing receptor with an increase in ITGB1 from 0 to 64.8%. Conclusions: The lack of correlation between the murine cell based TNA and the human cell based TNA results is an observation which warrants further investigation.
[1]. Martchenko et al., PNAS 2010 Aug 31;107(35):15583-8
[2]. Taylor J et al, poster presented at Health Protection Sept 2012
[3]. Kassam et al., Cellular Microbiology Volume 7, Issue 2, pages 281–292