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C Leclerc

Publications and source records attributed to C Leclerc.

190 records · Page 11Linked to original sources
PubMedDate not supplied

Immunogenicity of foreign peptide epitopes expressed in bacterial envelope proteins.

We have used two bacterial proteins from Escherichia coli to express heterologous peptides. Both proteins are situated in the E. coli cell envelope but have different properties: LamB is an integral outer membrane protein, and MalE a soluble periplasmic protein. The peptides were expressed as genetic inserts within "permissive sites" of these recipient proteins, i.e. sites which allow the insertion of foreign peptides without affecting the biological properties of the host protein. In this paper, we summarize preliminary rules governing the immunogenicity of resulting LamB and MalE hybrid proteins when expressed in E. coli. We focus on two model epitopes: either peptide 132-145 from the preS(2) region of hepatitis B virus or peptide 93-103 from poliovirus VP1 capsid protein. We also present first results obtained when the same hybrid proteins were expressed in attenuated Salmonella typhimurium. Plasmids encoding the hybrid proteins were transferred to aroA S.typhimurium by electroporation. In vitro, the hybrid proteins could be expressed at high levels by S. typhimurium. Mice were immunized by parenteral and oral routes. The effect of the carrier protein and the level of its expression on the in vivo behaviour of the immunizing bacteria and on the immune response induced will be discussed.

Animals↗
PubMedDate not supplied

Evaluation of the induction of specific cytotoxic T lymphocytes following immunization of F1 hybrid mice with rabies antigens.

The measurement of the production of cytotoxic T lymphocytes (CTL) induced in mice by rabies antigens currently uses spleen cells from immunized A/J mice as effector cells and infected neuroblastoma syngeneic cells as target cells. For several reasons, including difficulties in obtaining A/J mice, as well as genetic analysis of immune responses, it would be advantageous to use strains of mice other than the A/J mice. However, cell lines other than the neuroblastoma Neuro-2a line are difficult to infect by the rabies virus. Therefore, using the same target cells expressing the major histocompatibility complex H-2kd, we have developed an experimental system based on the induction of CTL in F1 BALB/c X C3H/HeJ hybrid H-2kd mice. Splenocytes from F1 hybrid mice primed with inactivated purified rabies virus (IPRV) exhibited cytotoxic activity specific for syngeneic infected target cells (Neuro-2a). High amounts of IPRV were required for the induction of CTL following in vivo priming. The antigen dose required for CTL induction was reduced by in vitro restimulation. In addition to specific CTL, a high level of natural killer cell activity was induced in F1 hybrid mice by priming with IPRV. Among rabies antigen preparations tested (IPRV, purified glycoprotein and ribonucleoprotein), only IPRV induced strong CTL stimulation.

Animals↗
PubMedDate not supplied

Percutaneous absorption of Mexoryl SX in human volunteers: comparison with in vitro data.

The potential human health risk of UV filters depends on their toxicity and the human systemic exposure which is a function of the extent of percutaneous absorption of the topically applied substance into the human organism. Using a 'mass balance' approach, a study was designed to investigate the systemically absorbed dose of [(14)C]-Mexoryl SX((R)) in humans after topical application of a typical sunscreen emulsion. In addition, to assess the correlation with in vitro experiments, the percutaneous absorption of this UVA filter through isolated human skin was measured under identical exposure conditions. When applied in vivo for a period of 4 h, 89-94% of the applied radioactivity was recovered from the wash-off samples. In urine samples, the radioactivity slightly exceeded background levels and corresponded maximally to 0.014% of the topically applied dose. No radioactivity was measured in blood or faeces sampled up to 120 h after application. In vitro, 24 h after a 4-hour application, [(14)C]-Mexoryl SX remained primarily on the skin surface. The mean in vitro absorption over 24 h, adding up the amounts found in the dermis and receptor fluid, was 0.16% of the applied dose. It is concluded from the in vivo pharmacokinetic results that the systemically absorbed dose of [(14)C]-Mexoryl SX is less than 0.1%. The order of magnitude of this value correlates well with the corresponding in vitro data which overestimate the in vivo results as previously observed with other hydrophilic compounds. This study demonstrates that, under realistic exposure conditions, the human systemic exposure to this UVA filter is negligible and poses no risk to human health.

Administration, Topical↗