In summary, we investigated the mechanism by which a mucosal vaccine based in recombinant LAB breaks the immunological tolerance of the gut in order to elicit a protective immune response. It is possible that mucosal tolerance may have been broken by two different mechanisms. In the first scenario, M cells might transport whole recombinant L. plantarum or OspA lipoprotein as it is released from lysed recombinant L. plantarum across the epithelium where they can induce primary immune responses [1] . In a second scenario, as dendritic cells uptake recombinant LAB and recognized it as the pathogen, the bacteria are no longer retained at the mesenteric lymphnode, as it happens when DCs are loaded with commensal bacteria, but instead migrate to secondary lymphoid tissue and present antigen to T-cells in a systemic environment that is not tolerigenic [49] . Neutralization of X4- and R5-tropic HIV-1 NL4-3 variants by HOCl-modified serum albumins BACKGROUND: Myeloperoxidase (MPO), an important element of the microbicidal activity of neutrophils, generates hypochlorous acid (HOCl) from H(2)O(2 )and chloride, which is released into body fluids. Besides its direct microbicidal activity, HOCl can react with amino acid residues and HOCl-modified proteins can be detected in vivo. FINDINGS: This report is based on binding studies of HOCl-modified serum albumins to HIV-1 gp120 and three different neutralization assays using infectious virus. The binding studies were carried out by surface plasmon resonance spectroscopy and by standard ELISA techniques. Virus neutralization assays were carried out using HIV-1 NL4-3 virus and recombinant strains with CXCR4 and CCR5 coreceptor usage. Viral infection was monitored by a standard p24 or X-gal staining assay. Our data demonstrate that HOCl-modified mouse-, bovine- and human serum albumins all bind to the HIV-1 NL4-3 gp120 (LAV) glycoprotein in contrast to non-modified albumin. Binding of HOCl-modified albumin to gp120 correlated to the blockade of CD4 as well as that of V3 loop specific monoclonal antibody binding. In neutralization experiments, HOCl-modified serum albumins inhibited replication and syncytium formation of the X4- and R5-tropic NL4-3 isolates in a dose dependent manner. CONCLUSIONS: Our data indicate that HOCl-modified serum albumin veils the binding site for CD4 and the V3 loop on gp120. Such masking of the viral gp120/gp41 envelope complex might be a simple but promising strategy to inactivate HIV-1 and therefore prevent infection when HOCl-modified serum albumin is applied, for example, as a topical microbicide. An important event in HIV-1 infection is the step-by-step binding of the external envelope complex, the gp120/ gp41 trimer, to (i) CD4 [1] and to (ii) a family of seventransmembrane chemokine receptors including CXCR4 and CCR5 which are the two major coreceptors [2] on the cellular membrane as well as to (iii) heparan sulfate structures [3] . HIV-1 entry can therefore be inhibited by heparan sulfate [4] , its analogs [5] or other synthetic polyanions [6] , ligands for CD4 [7] , CXCR4 [8] or CCR5 [9] , and by factors that bind to gp120 like neutralizing antibodies [10] . Since HIV-1 variability is prodigious, viral escape to all these antiviral substances has been documented and therefore there is a pressing need to find new strategies to efficiently block HIV-1 infection.