BACKGROUND: Parvovirus B19 (B19V) is a common contaminant of human plasma donations. Three B19V genotypes have been defined based on their DNA sequence. Reliable detection of Genotype 3 DNA has proved problematic because of unexpected sequence variability. B19V Genotype 3 is found primarily in West Africa, but was recently detected in plasma from a North American donor. The safety of plasma-derived medicinal products, with respect to B19V, relies on exclusion of high-titer donations, combined with virus clearance at specific manufacturing steps. Studies on inactivation of B19V are difficult to perform and inactivation of Genotype 3 has not yet been investigated. STUDY DESIGN AND METHODS: Inactivation of B19V Genotypes 3 and 1 by pasteurization of human serum albumin and incubation at low pH was studied using a cell culture assay for infectious virus particles. Infected cells were detected by reverse transcription-polymerase chain reaction analysis of virus capsid mRNA. Neutralization of B19V Genotype 3 was investigated using human immunoglobulin preparations. RESULTS: Genotypes 1 and 3 displayed comparable inactivation kinetics during pasteurization of albumin at 56°C, as well as by incubation at various low-pH conditions (pH 4.2 at 37°C and pH 4.5 at 23°C, respectively) used in immunoglobulin manufacturing. Both Genotypes were readily neutralized by pooled immunoglobulin preparations of North American or European origin. CONCLUSION: Pasteurization and low-pH treatment were equally effective in inactivating B19V Genotypes 1 and 3. Neutralization experiments indicated that pooled immunoglobulin of North American or European origin is likely to be equally effective in treatment of disease induced by both genotypes.
BACKGROUND:Parvovirus B19 (B19V) is a common contaminant of human plasma donations. Three B19V genotypes have been defined based on their DNA sequence. Reliable detection of Genotype 3 DNA has proved problematic because of unexpected sequence variability. B19V Genotype 3 is found primarily in West Africa, but was recently detected in plasma from a North American donor. The safety of plasma-derived medicinal products, with respect to B19V, relies on exclusion of high-titer donations, combined with virus clearance at specific manufacturing steps. Studies on inactivation of B19V are difficult to perform and inactivation of Genotype 3 has not yet been investigated. STUDY DESIGN AND METHODS: Inactivation of B19V Genotypes 3 and 1 by pasteurization of human serum albumin and incubation at low pH was studied using a cell culture assay for infectious virus particles. Infected cells were detected by reverse transcription-polymerase chain reaction analysis of virus capsid mRNA. Neutralization of B19V Genotype 3 was investigated using human immunoglobulin preparations. RESULTS: Genotypes 1 and 3 displayed comparable inactivation kinetics during pasteurization of albumin at 56°C, as well as by incubation at various low-pH conditions (pH 4.2 at 37°C and pH 4.5 at 23°C, respectively) used in immunoglobulin manufacturing. Both Genotypes were readily neutralized by pooled immunoglobulin preparations of North American or European origin. CONCLUSION: Pasteurization and low-pH treatment were equally effective in inactivating B19V Genotypes 1 and 3. Neutralization experiments indicated that pooled immunoglobulin of North American or European origin is likely to be equally effective in treatment of disease induced by both genotypes.