CREATING CONFIDENCE

RESEARCH

Calibration of chimpanzee plasmas of known infectivity

An important driver of residual transmission risk by blood transfusion is the viral infectivity in blood. We compared Japanese chimpanzee plasma’s with a known infectivity titer to the VQC-Sanquin standards and according to this calibration experiment the 50% chimpanzee minimum infectious dose (CID50) (and range) was determined at 4.0 (1.3-12.6) and 8.1 (2.6-25.6) copies or virions for HBV and HCV respectively. According to recalibration of a very low HCV concentration in a pool of pre-ramp up samples we estimated that 14 (instead of 60) HCV virions were infectious in a chimpanzee, indicating that the CID50 (range) could be as low as 4.4 (1.4-14) virions. For worst case window period risk modelling we therefore assumed a 50% minimum infectious dose (MID50) of 3.16 (range between 1 and 10) virions or copies for both HBV or HCV. A similar worst case MID50 of 3.16 (1-10) virions was estimated from SIV infectivity studies in macaques, but the infectivity of HIV is estimated to be 10-100 fold lower in stored cellular blood components.

The calibration data of the chimpanzee infectivity plasma’s against the VQC-Sanquin standards are described in this validation report (PDF).