BackgroundThe availability of a universal influenza vaccine able to induce broad cross-reactive immune responses against diverse influenza viruses would provide an alternative to currently available strain-specific vaccines. We evaluated the ability of vectors based on modified vaccinia virus Ankara (MVA) expressing conserved influenza proteins to protect mice against lethal challenge with multiple influenza subtypes.MethodsMice were immunized with MVA vectors expressing H5N1-derived nucleoprotein (NP), the stem region of hemagglutinin (HA), matrix proteins 1 and 2 (M1 and M2), the viral polymerase basic protein 1 (PB1), or the HA stem fused to a quadrivalent matrix protein 2 extracellular domain (M2e). Immunized mice were challenged with lethal doses of H5N1, H7N1 or H9N2 virus and monitored for disease symptoms and weight loss. To investigate the influence of previous exposure to influenza virus on protective immune responses induced by conserved influenza proteins, mice were infected with pandemic H1N1 virus (H1N1pdm09) prior to immunization and subsequently challenged with H5N1 virus. Antibody and T cell responses were assessed by ELISA and flow cytometry, respectively.ResultsMVA vectors expressing NP alone, or co-expressed with other conserved influenza proteins, protected mice against lethal challenge with H5N1, H7N1 or H9N2 virus. Pre-exposure to H1N1pdm09 increased protective efficacy against lethal H5N1 challenge. None of the other conserved influenza proteins provided significant levels of protection against lethal challenge. NP-expressing vectors induced high numbers of influenza-specific CD4+ and CD8+ T cells and high titer influenza-specific antibody responses. Higher influenza-specific CD4+ T cell responses and NP-specific CD8+ T cell responses were associated with increased protective efficacy.ConclusionsMVA vectors expressing influenza NP protect mice against lethal challenge with H5N1, H7N1 and H9N2 viruses by a mechanism involving influenza-specific CD4+ and CD8+ T cell responses.
After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC.
synthesis from amino acids has been shown to occur in aqueous solutions at high concentrations of sodium chloride and in the presence of Cu(ll) after several days at 85°C, under nitrogen or air as well. Di-and tripeptides could be obtained in a series of experiments which have yet to be optimized. However, these experiments have proved the principle applicability of a model which is based on the structural features of concentrated aqueous NaCI solutions and evidence of catalytic effects in peptide condensation reactions exerted by di-and trivalent metal ions. Among the ions of Mg, Ca, Cr, Mn, Co, Ni, Fe, Cu, Zn and Cd, only copper was found to be active under these conditions. This leads to new aspects for possible prebiotic peptide syntheses based on a very simple system of only water, amino acids and mineral salts.
Abstract. The recently reported condensation reaction of glycine to di-and triglycine in aqueous solution in the presence of higher concentrations of sodium chloride and copper ions has been investigated systematically and quantitatively using HPLC analytical methods. The influence of'environmental' factors (temperature, concentration, atmosphere) are discussed. Numerous other metal ions have been investigated with respect to similar catalytic effects, and molybdenum results as the only one inducing peptide condensation, although to a much lesser extent. Experiments based on evaporation of water and redissolution lead to peptide condensation up to (gly)6 in concentrated solutions and produces peptides even starting from initially low concentrations.
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