Antibodies against Hepatitis A and Hepatitis B Virus in Intravenous Immunoglobulin Products

Abstract

The worldwide seroprevalence of hepatitis A virus (HAV) and hepatitis B virus (HBV) has changed over the last two decades, indicating a declining incidence of HAV and HBV infections. Therefore, vaccinations against HAV and HBV are recommended for unimmunized people before traveling to an endemic area. Unfortunately, primary antibody deficiency (PAD) patients can only obtain humoral immunity through intravenous immunoglobulin G (IVIG) replacement and not from vaccination because of a defect in antibody production. However, few studies have analyzed the titers of antibodies against HAV or HBV in IVIG products. In this study, the titers of anti-HAV and anti-HBs antibodies were measured in nineteen lots of IVIG products from five manufacturers from three countries (A, B from Korea; C, D from Japan; and E from the USA), and trough titers in plasma were estimated. Concentrations of anti-HAV antibody ranged from 1,888–8,927 mIU/mL and estimated trough titers exceeded the minimal protective value in all evaluated IVIG products. Concentrations of anti-HBs antibody ranged from 438–965 mIU/mL in products A and B and were 157, 123, and 1,945 mIU/mL in products C, D, and E, respectively. Estimated trough titers in products A, B, and E exceeded the minimal protective value but those in products C and D did not reach this threshold. These data demonstrated that available IVIG products generally provide sufficient antibodies against HAV and HBV to protect patients with PAD, although the trough concentrations of anti-HBs antibody in two IVIG products did not reach the minimum protective value.

Antibodies to vaccine antigens in pooled polyclonal human IgG products

“…Results for Japanese and Korean products from Lee et al seem below this range, particularly for HBV. 45 The discrepancies between that study and the earlier studies may be due to technical differences in the way the assays were performed, differences in immunization practices in different countries, or other factors, and should be studied further. In studies in which results from multiple lots of the same product were reported, the coefficients of variation amongst the lots are generally within 25%.…”

“…As shown in panel B, neutralizing anti‐HAV titers in final containers of a single IgG product show a similar and highly significant (p < 0.0001) difference depending on whether the product was made from plasma from EU (left) vs US plasma (right) . Despite the data showing that IgG derived from US plasma has only half as much neutralizing antibody as EU‐derived IgG, even the titer in the US product, 14.6 IU/mL, is > 1000 fold higher than that needed to provide a minimal protective level of 10 mIU/ml in recipients' plasma …”

“…In studies in which results from multiple lots of the same product were reported, the coefficients of variation amongst the lots are generally within 25% . Antibody to HBV surface antigen (HBsAg) titers in the different studies also generally fall with a two‐fold range, centered just under 2 IU/mL . (Table ) Data from PIDD patients receiving different IgG preparations at doses of 400 mg/kg every 3–4 weeks suggests that most patients maintain anti‐HBsAg titers above protective levels of 100 IU/L throughout their dosing intervals …”

“…Actual determinations of trough antibody levels in PIDD patients or calculations suggest that all of these would result in protective levels. Results for Japanese and Korean products from Lee et al seem below this range, particularly for HBV . The discrepancies between that study and the earlier studies may be due to technical differences in the way the assays were performed, differences in immunization practices in different countries, or other factors, and should be studied further.…”

“…The discrepancies between that study and the earlier studies may be due to technical differences in the way the assays were performed, differences in immunization practices in different countries, or other factors, and should be studied further. In studies in which results from multiple lots of the same product were reported, the coefficients of variation amongst the lots are generally within 25% . Antibody to HBV surface antigen (HBsAg) titers in the different studies also generally fall with a two‐fold range, centered just under 2 IU/mL .…”