Seyoum Ayehunie

Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection.

Although maternal human immunodeficiency virus type 1 (HIV-1) transmission occurs during gestation, intrapartum and postpartum (by breast-feeding), 50–70% of all infected children seem to acquire HIV-1 shortly before or during delivery. Epidemiological evidence indicates that mucosal exposure is an important aspect of intrapartum HIV transmission. A simian immunodeficiency virus (SIV) macaque model has been developed that mimics the mucosal exposure that can occur during intrapartum HIV-1 transmission. To develop immunoprophylaxis against intrapartum HIV-1 transmission, we used SHIV–vpu+ (refs. 5,6), a chimeric simian–human virus that encodes the env gene of HIV-IIIB. Several combinations of human monoclonal antibodies against HIV-1 have been identified that neutralize SHIV–vpu+ completely in vitro through synergistic interaction. Here, we treated four pregnant macaques with a triple combination of the human IgG1 monoclonal antibodies F105, 2G12 and 2F5. All four macaques were protected against intravenous SHIV–vpu+ challenge after delivery. The infants received monoclonal antibodies after birth and were challenged orally with SHIV–vpu+ shortly thereafter. We found no evidence of infection in any infant during 6 months of follow-up. This demonstrates that IgG1 monoclonal antibodies protect against mucosal lentivirus challenge in neonates. We conclude that epitopes recognized by the three monoclonal antibodies are important determinants for achieving substantial protection, thus providing a rational basis for AIDS vaccine development.

Inhibition of HIV-1 replication by an aqueous extract of Spirulina platensis (Arthrospira platensis).

An aqueous extract of the blue-green filamentous algae Arthrospira platensis (previously called Spirulina platensis) inhibited HIV-1 replication in human T-cell lines, peripheral blood mononuclear cells (PBMC), and Langerhans cells (LC). Extract concentrations ranging between 0.3 and 1.2 microg/ml reduced viral production by approximately 50% (50% effective concentration [EC50]) in PBMCs. The 50% inhibitory concentration (IC50) of extract for PBMC growth ranged between 0.8 and 3.1 mg/ml. Depending on the cell type used, therapeutic indices ranged between 200 and 6000. The extract inactivated HIV-1 infectivity directly when preincubated with virus before addition to human T-cell lines. Fractionation of the extract revealed antiviral activity in the polysaccharide fraction and also in a fraction depleted of polysaccharides and tannins. We conclude that aqueous A platensis extracts contain antiretroviral activity that may be of potential clinical interest.

Relationship between cell-free viraemia, antigenaemia and antibody levels in HIV-1-infected Ethiopian patients.

ObjectiveTo determine the relationship and occurrence of cell-free viraemia, free or immune-complexed p24-antigen and p24-antibody levels in blood from HIV-1-infected patients in Ethiopia. MethodsPeripheral blood was obtained from 66 Ethiopian and 137 Swedish HIV-1-seropositive patients. Blood samples were analysed for free or immune-complex bound p24 antigen by enzyme-linked immunosorbent assay before and after acid hydrolysis of immune complexes for infectious virus in plasma and peripheral blood mononuclear cells (PBMC), and for p24-antibody levels. We compared the kinetics of viral replication of Ethiopian with Swedish isolates in vitro. ResultsInfectious virus was isolated from PBMC in 95% and from plasma in 81% of Ethiopian AIDS patients. In contrast, p24 antigen was detected in only 5% of AIDS patients from Ethiopia, compared with 76% of those from Sweden. p24-antibody levels were much higher and more persistent in Ethiopian than in Swedish subjects. The ratio between reverse transcriptase activity and p24 antigen was significantly higher in Ethiopian isolate culture than in those of the Swedish isolates. ConclusionsOur results show that relationships between viraemia, p24 antigenaemia and p24-antibody levels in HIV-1-infected Ethiopian patients differ from those found in comparable Swedish patients. This pattern may partly explain the differences seen in the natural course of HIV-1 infection in Ethiopia and Sweden.