Baboon envelope pseudotyped lentiviral vectors efficiently transduce human B cells and allow active factor IX B cell secretion in vivo in NOD/SCIDγc-/- mice.

Essentials B cells are attractive targets for gene therapy and particularly interesting for immunotherapy. A baboon envelope pseudotyped lentiviral vector (BaEV-LV) was tested for B-cell transduction. BaEV-LVs transduced mature and plasma human B cells with very high efficacy. BaEV-LVs allowed secretion of functional factor IX from B cells at therapeutic levels in vivo. SUMMARY: Background B cells are attractive targets for gene therapy for diseases associated with B-cell dysfunction and particularly interesting for immunotherapy. Moreover, B cells are potent protein-secreting cells and can be tolerogenic antigen-presenting cells. Objective Evaluation of human B cells for secretion of clotting factors such as factor IX (FIX) as a possible treatment for hemophilia. Methods We tested here for the first time our newly developed baboon envelope (BaEV) pseudotyped lentiviral vectors (LVs) for human (h) B-cell transduction following their adaptive transfer into an NOD/SCIDγc-/- (NSG) mouse. Results Upon B-cell receptor stimulation, BaEV-LVs transduced up to 80% of hB cells, whereas vesicular stomatitis virus G protein VSV-G-LV only reached 5%. Remarkably, BaEVTR-LVs permitted efficient transduction of 20% of resting naive and 40% of resting memory B cells. Importantly, BaEV-LVs reached up to 100% transduction of human plasmocytes ex vivo. Adoptive transfer of BaEV-LV-transduced mature B cells into NOD/SCID/γc-/- (NSG) [non-obese diabetic (NOD), severe combined immuno-deficiency (SCID)] mice allowed differentiation into plasmablasts and plasma B cells, confirming a sustained high-level gene marking in vivo. As proof of principle, we assessed BaEV-LV for transfer of human factor IX (hFIX) into B cells. BaEV-LVs encoding FIX efficiently transduced hB cells and their transfer into NSG mice demonstrated for the first time secretion of functional hFIX from hB cells at therapeutic levels in vivo. Conclusions The BaEV-LVs might represent a valuable tool for therapeutic protein secretion from autologous B cells in vivo in the treatment of hemophilia and other acquired or inherited diseases.

Antibiotic prophylaxis against postpartum endometritis after vaginal delivery: a prospective randomized comparison between Amox-CA (Augmentin) and abstention.

The most common adverse outcome associated with vaginal delivery is endometritis. It plays a significant role in postpartum morbidity and mortality. There is considerable evidence to support the idea that a single dose of antibiotic after vaginal delivery might decrease the incidence of postpartum endometritis. In this study the evaluation of the efficacy of antibiotic prophylaxis was based upon comparison of a group of patients given a single dose of Amox-CA (Augmentin) with a group of patients without treatment. The study was performed in the Department of Obstetrics and Gynecology of the A. Béclère Public Hospital, Clamart, France (Paris-Sud University). The patients who were the subject of the study had delivered vaginally during the period of 1 year, and were free of any clinical diagnosis of chorioamnionitis or other extragenital infection, had a maternal temperature of less than 38 degrees C during labor and 1 h after delivery, and had no history of allergy to penicillins or cephalosporins. After application of exclusion criteria, 1373 patients were randomized and 1291 included 610 in Group I given Amox-CA and 681 in Group II without any antibiotic. A single dose of 1.2 g of Amox-CA was given by intravenous injection, 1 h after delivery, in Group I. Patients of Group II received no injection. Postpartum status was evaluated before the patient left hospital and 2 weeks later. The two groups were similar in terms of demographic and clinical parameters. Four patients developed endometritis in Group I (4/610, 0.66%). Sixteen patients in Group II developed endometritis (16/680, 2.38%) (P = 0.013; 95% confidence interval (CI), 0.36-3.08%).(ABSTRACT TRUNCATED AT 250 WORDS)

[B virus, delta agent and human immunodeficiency virus infections in drug addicts]. / Les infections à virus B et delta et à virus de l'immunodéficience humaine chez les toxicomanes.

Infections with the B, D, A, NANB viruses and with the human immunodeficiency virus (HIV) are very common among drug addicts, some of whom may harbour several of these pathogens. The serum of 90 per cent of drug addicts contains one of the HBV markers, and 20 per cent of them carry an anti-D antibody which is more often present in HBs Ag-positive subjects but may also be found in those who are positive for anti-HBs and anti HBc antibodies. The presence of an anti-delta antibody increases the risk of severe histological lesions (chronic active hepatitis, cirrhosis), as does chronic alcoholism associated with drug addiction. Fifty to sixty per cent of drug addicts are seropositive for HIV. At the AIDS stage, hepatic lesions are extremely frequent (90 per cent), but they have low activity and are seldom responsible for death.