Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.

Unlabelled: Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101).

Potential and limitation of UVC irradiation for the inactivation of pathogens in platelet concentrates.

Background: Pathogen contamination, causing transfusion-transmitted diseases, is an ongoing concern in transfusion of cellular blood products. In this explorative study, the pathogen-inactivating capacity of UVC irradiation in platelet (PLT) concentrates was investigated. The dose dependencies of inactivation of several viruses and bacteria were compared with the effect on PLT quality.

Viral safety of C1-inhibitor NF.

We studied the efficacy of virus reduction by three process steps (polyethylene glycol 4000 (PEG) precipitation, pasteurization, and 15nm virus filtration) in the manufacturing of C1-inhibitor NF. The potential prion removing capacity in this process was estimated based on data from the literature. Virus studies were performed using hepatitis A virus (HAV) and human immunodeficiency virus (HIV) as relevant viruses and bovine viral diarrhea virus (BVDV), canine parvovirus (CPV) and pseudorabies virus (PRV) as model viruses, respectively.

Differential sensitivities of pathogens in red cell concentrates to Tri-P(4)-photoinactivation.

Background And Objectives: Photodynamic treatment (PDT) with the cationic porphyrin, mono-phenyl-tri-(N-methyl-4-pyridyl)-porphyrin chloride [Tri-P(4)], has previously been shown to be effective at inactivating vesicle stomatitis virus (VSV) in red cell concentrates (RCC) with limited damage to red blood cells (RBC). The aim of this study was to determine the pathogen-inactivating capacity of PDT with Tri-P(4) for a broader range of pathogens and to establish the associated effect on in vitro RBC quality.

Materials And Methods: A series of viruses and bacteria was spiked into 60% RCC.

Viral safety of Nanogam, a new 15 nm-filtered liquid immunoglobulin product.

Background And Objectives: Producers of plasma derivatives continuously improve the viral safety of their products by, for example, introducing additional virus-reducing steps into the manufacturing process. Here we present virus-elimination studies undertaken for a number of steps employed in a new manufacturing process for liquid intravenous immunoglobulin (Nanogam) that comprises two specific virus-reducing steps: a 15-nm filtration step combined with pepsin treatment at pH 4.4 (pH 4.

Standards for the assay of Creutzfeldt-Jakob disease specimens.

Assays for the agent of Creutzfeldt-Jakob disease (CJD) include measurement of infectivity in different animal systems, such as wild-type or transgenic mice, and detection of PrP(Sc) by different methods and formats. The various assays could be best calibrated against each other by use of uniform readily available materials, and samples of four human brains, two from sporadic CJD patients, one from a variant CJD patient and one from a non-CJD patient, have been prepared as 10% homogenates dispensed in 2000 vials each for this purpose. Results of in vitro methods, particularly immunoblot assays, were compared in the first collaborative study described here.

Additive effects of dipyridamole and Trolox in protecting human red cells during photodynamic treatment.

Background And Objectives: Photodynamic treatment (PDT) of red blood cell (RBC) suspensions has been reported to result in virus inactivation, but also in deterioration of cell quality. Recently, we have demonstrated the potential usefulness of the reactive oxygen species scavenger dipyridamole in selectively protecting RBCs against the harmful side-effects of PDT. Unfortunately, dipyridamole-conferred protection against long-term photohaemolysis was incomplete.

The band III ligand dipyridamole protects human RBCs during photodynamic treatment while extracellular virus inactivation is not affected.

Background: Recently, the potential usefulness of dipyridamole (DIP) in protecting RBCs against the harmful side effects of photodynamic sterilization was demonstrated. In the present study, the use of DIP for selective protection of RBCs was investigated under conditions more relevant for blood bank practice.

Study Design And Methods: WBC-reduced RBC suspensions (30% Hct) were treated with 1,9-dimethylmethylene blue and red light, and the influence of the inclusion of DIP on photohemolysis was assessed as a function of sensitizer concentration, light dose, and storage time.

The virucidal spectrum of a high concentration alcohol mixture.

The virucidal spectrum of a high concentration alcohol mixture (80% ethanol and 5% isopropanol) was determined for a broad series of lipid-enveloped (LE) and non-lipid-enveloped (NLE) viruses covering all relevant blood-borne viruses. LE viruses were represented by human immunodeficiency virus (HIV), bovine viral diarrhoea virus (BVDV), a specific model virus for hepatitis C virus (HCV), pseudorabies virus (PRV), and vaccinia virus. For the NLE viruses hepatitis A virus, canine parvovirus (a model for human parvovirus B19), and reovirus type 3 (Reo-3) were used.

Inhibition of HIV-1 IIIB and clinical isolates by human parotid, submandibular, sublingual and palatine saliva.

Human saliva is known to possess components that decrease the HIV-1 infectivity in vitro. The mechanism of how these components inhibit the infectivity is still not clear on the molecular level. The purpose of this study was to discriminate between serous and mucous components with respect to inhibitory capacity and site of action.

Virus validation of pH 4-treated human immunoglobulin products produced by the Cohn fractionation process.

To assess the virus reducing capacity of Cohn's cold ethanol fractionation process for the production of intravenous (IVIg) and intramuscular (IMIg) immunoglobulin products, and treatment of these products at pH 4, a validation study of virus removal and/or inactivation was performed using both lipid-enveloped viruses [human immunodeficiency virus (HIV), bovine viral diarrhoea virus (BVDV) and pseudorabies virus (PSR)], and non-lipid-enveloped viruses [(simian virus 40 (SV40) and encephalomyocarditis virus (EMC)]. For the cold ethanol fractionation process, overall reduction factors of 3.0 logs, > or = 2.

A polymerase chain reaction (PCR) assay for the detection of bovine herpesvirus 1 (BHV1) in selectively digested whole bovine semen.

A PCR assay for the detection of bovine herpesvirus type 1 (BHV1) DNA in selectively digested whole bovine semen was developed and evaluated. A brief treatment with proteinase-K was used to lyse free virus, virus present in non-sperm cells and virus adhering to the spermatozoa. Genomic bovine DNA was not released by this treatment.

Virulence and immunogenicity in calves of thymidine kinase- and glycoprotein E-negative bovine herpesvirus 1 mutants.

A deletion was introduced into the thymidine kinase (TK) gene of the BHV1 strain Lam and, or, the complete coding region of the glycoprotein E (gE) gene was deleted to reduce virulence and to make serological differentiation possible. The virulence and immunogenicity of these three BHV1 mutants (TK-, gE- and TK-/gE) were studied in specific-pathogen-free calves. Although inactivation of TK strongly reduced the virulence of the Lam strain, deletion of the gE gene alone sufficed to yield complete attenuation of the Lam strain for seven-week-old calves.

A glycoprotein E deletion mutant of bovine herpesvirus 1 infects the same limited number of tissues in calves as wild-type virus, but for a shorter period.

To gain insight into the role of glycoprotein E of bovine herpesvirus 1 (BHV-1), we compared the distribution of wild-type (wt) BHV-1 with that of a gE deletion mutant (gE-) in calves after intranasal inoculation. The wt-infected calves had severe clinical signs, but the gE(-)-infected calves were virtually free of clinical signs. At 3, 4, 7, 8, 44, 45, 50 and 51 days post-infection (p.

Excretion of bovine herpesvirus 1 in semen is detected much longer by PCR than by virus isolation.

To compare the sensitivities of PCR and virus isolation and to examine the course of virus excretion in semen, we intrapreputially inoculated eight bulls with bovine herpesvirus 1 (BHV1) and used two bulls as sentinels. From these bulls, we collected a large panel of semen samples during 65 days postinfection (dpi). At 44 dpi the bulls received dexamethasone to reactivate putatively latent virus.

A glycoprotein E deletion mutant of bovine herpesvirus 1 is avirulent in calves.

A marker vaccine elicits an antibody response in the host that can be distinguished from the antibody response induced by a wild-type strain. To obtain a bovine herpesvirus 1 (BHV-1) marker vaccine, we constructed a glycoprotein E (gE) deletion mutant. This was obtained by removing the complete gE coding region from the BHV-1 genome.

Development of a rapid and sensitive polymerase chain reaction assay for detection of bovine herpesvirus type 1 in bovine semen.

We developed a polymerase chain reaction (PCR) assay to detect bovine herpesvirus type 1 (BHV-1) in bovine semen. Since bovine semen contains components that inhibit PCR amplification, a protocol was developed to purify BHV-1 DNA from bovine semen. To identify failures of PCR amplification, we used an internal control template that was coamplified by the same PCR primers.

Tryptophan auxotrophic mutants in Aspergillus niger: inactivation of the trpC gene by cotransformation mutagenesis.

Aspergillus niger tryptophan auxotrophic mutants have been isolated after UV irradiation of conidiospores. The mutants belong to two different complementation groups, trpA and trpB, which complement each other in heterokaryons. Neither of the mutations could be complemented with the cloned A.