Abstract
Despite the success of postexposure prophylaxis (PEP) of the newborn in preventing mother-to-child transmission of hepatitis B virus), in non-US clinical trials, administering hepatitis B immune globulin (HBIG) to mothers at the end of pregnancy (in addition to passive-active PEP of the newborn) only partially improved outcomes. That is, a significant percentage of newborns became infected during their first year of life. We used a relevant animal model for human IgG transplacental transfer to study dose, time and subclass dependence of HBV neutralizing antibody (nAb) maternal, and fetal levels at the end of pregnancy. Pregnant guinea pigs received 50 or 100 IU/kg HBIGIV 2–5 days before delivery. Human total IgG, IgG subclasses, and nAb in mothers and their litters were measured. In vitro analyses of guinea pig Fc neonatal receptor binding to HBIGIV, as well as to all human IgG subclasses, were also performed. Our study showed that nAb transferred transplacentally from the pregnant guinea pigs to their litters; no transfer occurred during parturition. The amount of the transferred nAb was dose and time dependent. Thus, selection of an efficacious dose in the clinic is important: microdosing may be underdosing, particularly in cases of high viraemia.
Highlights
Chronic hepatitis B is a serious viral disease, associated with a high risk for developing liver cirrhosis and hepatocellular carcinoma [1,2,3]
Because 90% of infants infected at birth develop chronic Hepatitis B virus (HBV) infection and 25% of those die prematurely from cirrhosis or liver cancer [5, 6], failure to prevent infection following perinatal exposure to HBV carries a heavy burden to the individual, family, and society at large
Passive-active postexposure prophylaxis (PEP) with HBIG and hepatitis B vaccine is 85–95% effective in preventing vertical transmission of HBV compared to 70–95% prevention rate for the vaccine alone [6, 7]
Summary
Chronic hepatitis B is a serious viral disease, associated with a high risk for developing liver cirrhosis and hepatocellular carcinoma [1,2,3]. Using HBIG at the end of pregnancy has not yielded significant reductions in HBV neonatal infection rates of vaccinated babies by the time they reach one year of age [10]. Intrigued by these reports, we set out to characterize HBV neutralizing antibody levels and pharmacokinetic characteristics in the mother and her newborn, respectively, after HBIG administration in an animal model of pregnancy. This finding has implications when considering an efficacious dose in the clinic
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