Impact of chemiluminescent enzyme immunoassay screening for human parvovirus B19 antigen in Japanese blood donors.

Background: To reduce the risk of human parvovirus B19 (B19V) transmission through contaminated blood for transfusion and plasma-derived products, the Japanese Red Cross (JRC) Blood Centers introduced B19V antigen screening by chemiluminescent enzyme immunoassay (CLEIA-B19V) in 2008.

Study Design And Methods: Donor samples that were positive by CLEIA-B19V screening were tested for B19V DNA. The sensitivity of CLEIA-B19V was tested using samples of all three genotypes and B19V DNA-positive donations.

Persistent growth of a human plasma-derived hepatitis C virus genotype 1b isolate in cell culture.

HCV (hepatitis C virus) research, including therapeutics and vaccine development, has been hampered by the lack of suitable tissue culture models. Development of cell culture systems for the growth of the most drug-resistant HCV genotype (1b) as well as natural isolates has remained a challenge. Transfection of cultured cells with adenovirus-associated RNA(I) (VA RNA(I)), a known interferon (IFN) antagonist and inhibitor of dsRNA-mediated antiviral pathways, enhanced the growth of plasma-derived HCV genotype 1b.

Parvovirus B19 infection transmitted by transfusion of red blood cells confirmed by molecular analysis of linked donor and recipient samples.

Background: Extremely high viremic levels of parvovirus B19 (B19V) can be found in acutely infected, but asymptomatic donors. However, reports of transmission by single-donor blood components are rare. In this prospective study, paired donor-recipient samples were used to investigate the transfusion risk.

West Nile virus infection in plasma of blood and plasma donors, United States.

This study investigated the association of ongoing West Nile virus (WNV) infections with neutralizing antibody titers in US plasma-derived intravenous immune globulin released during 2003-2008. Titers correlated closely with the prevalence of past WNV infection in blood donors, with 2008 lots indicating a prevalence of 1%.

A linked donor-recipient study to evaluate parvovirus B19 transmission by blood component transfusion.

Parvovirus B19V infection can be a serious infection for hematology patients with underlying hemolysis or compromised erythropoiesis syndromes. Although case reports of B19V transmission by blood component transfusion (as contrasted to manufactured plasma derivatives) are rare, no studies have systematically determined a rate of transmission to recipients transfused with B19V DNA-positive components. We used a linked donor and recipient repository and a sensitive, quantitative B19V DNA polymerase chain reaction (PCR) assay to assess such transmission in B19V-susceptible (ie, anti-B19V immunoglobulin G [IgG] negative) recipients.

A simple and rapid Hepatitis A Virus (HAV) titration assay based on antibiotic resistance of infected cells: evaluation of the HAV neutralization potency of human immune globulin preparations.

Background: Hepatitis A virus (HAV), the causative agent of acute hepatitis in humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV titrations are laborious and time-consuming because the virus in general does not cause cytopathic effect and is detected by immunochemical or molecular probes. Simple HAV titration assays could be developed using currently available viral construct containing selectable markers.

Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma.

Neutralizing antibodies directed against hepatitis C virus (HCV) are present in Igs made from anti-HCV-positive plasma. However, these HCV-specific Igs are largely ineffective in vivo. The mechanism for the poor effectiveness is currently unknown.

Parvovirus B19 DNA in Factor VIII concentrates: effects of manufacturing procedures and B19 screening by nucleic acid testing.

Background: Parvovirus B19 (B19) is a common contaminant, especially in coagulation factors. Because of B19 transmission by pooled plasma, solvent/detergent treated in 1999, some fractionators initiated minipool nucleic acid testing (NAT) to limit the B19 load in manufacturing pools. In this study, the extent of B19 DNA contamination in commercial Factor VIII concentrates, that is, antihemophilic factor (human) (AHF), manufactured before and after B19 NAT screening was implemented, was determined.

Quantification of hepatitis B virus genomes and infectivity in human serum samples.

Background: Hepatitis B virus (HBV) infections are still a major health issue, with approximately 350 million people chronically infected with HBV worldwide. Information about the minimum copy number of HBV genomes required for infection would be useful as a reference for drug and vaccine development; for monitoring HBV patients during treatment; for screening of blood, organ, and tissue donors; and for regulating nucleic acid amplification assays for HBV.

Study Design And Methods: Serum samples from chronic carriers (hepatitis B surface antigen-positive and antibody to HBV core antigen-positive) of the three most common subtypes of HBV were studied; their infectivity titers had been evaluated previously in chimpanzees.

Measles-virus-neutralizing antibodies in intravenous immunoglobulins.

Measles infection induces lifelong immunity; however, wild-type infection stimulates higher levels of measles-virus-neutralizing antibodies (mnAbs) than does vaccination. Because the proportion of the donor population with vaccine-induced measles immunity is increasing, this study was conducted to determine whether this shift in demographic characteristics affects mnAb levels in contemporary lots of Immune Globulin Intravenous (Human) (IGIV). When 166 lots of 7 IGIV products manufactured between 1998 and 2003 were assayed by plaque-reduction neutralization test, there was a progressive decrease in geometric mean titers in lots manufactured between 1999 and 2002.

Neutralization epitope responsible for the hepatitis B virus subtype-specific protection in chimpanzees.

Neutralizing monoclonal antibody (BX-182) directed against the d determinant of hepatitis B virus (HBV) surface antigen protected chimpanzees from infection by HBV subtype adw but not by subtype ayw, as demonstrated by intravenously inoculating a mixture of the antibody with the respective subtype of the virus. To elucidate the mechanism underlying the subtype-specific protection, a combinatorial approach of screening random peptide phage libraries, bioinformatics, and structure analysis was used in this study to identify the neutralization epitope responsible for the observed protection. The epitope was mapped at the N terminus of the pre-S1 region of the hepatitis B surface antigen between residues 17 and 21, of which the residues Val-18/Pro-19 were critical for antibody binding.

International collaborative study to assess candidate reference preparations to control the level of anti-D in IVIG for use in Europe and the United States.

Regulatory requirements to control the level of anti-D in intravenous immunoglobulin (IVIG) products with European and United States (US) licences are to be introduced. A reference preparation of IVIG containing anti-D at 0.0475 IU/ml and having a nominal titre of 8 using the proposed direct haemagglutination reference method was deemed suitable to define the anti-D limit.

Parvovirus B19 transmission by a high-purity factor VIII concentrate.

Background: Parvovirus B19 (B19) is known to cause a variety of human diseases in susceptible individuals by close contact via the respiratory route or by transfusion of contaminated blood or blood products. In this study, whether a case of B19 transmission was causally related to the infusion of implicated lots of a solvent/detergent (S/D)-treated, immunoaffinity-purified factor VIII concentrate (antihemophilic factor [human][AHF]) was investigated.

Study Design And Methods: Anti-B19 (both immunoglobulin M [IgM] and immunoglobulin G [IgG]) and B19 DNA (by a nucleic acid testing [NAT] procedure) were assayed in two implicated product lots, a plasma pool, and a recipient's serum sample.

Neutralizing antibodies to hepatitis C virus (HCV) in immune globulins derived from anti-HCV-positive plasma.

The role of humoral immunity in hepatitis C virus (HCV) infections is uncertain. Nevertheless, there is increasing evidence for neutralizing antibodies to HCV in the serum or plasma of chronically infected individuals. Immune globulins prepared by ethanol fractionation of plasma had long been considered safe until a commercial immune globulin product, Gammagard, prepared from plasma from which units containing anti-HCV had been excluded, transmitted HCV to recipients.