Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous work has shown that agonistic Abs to CD40 (anti-CD40) can boost weak CD8 T cell responses as well as substitute for CD4 T cell function during chronic gammaherpes virus infection. Agonistic anti-CD40 treatment has, therefore, been suggested as a potential therapeutic strategy in immunocompromised patients. In this study, we investigated whether agonistic anti-CD40 could substitute for CD4 T cell help in generating a sustained CD8 T cell response and prevent viral recrudescence following infection with lymphocytic choriomeningitis virus (LCMV). Contrary to expectations, we found that anti-CD40 treatment of MHC class II-deficient mice infected with a moderate dose of LCMV resulted in severe suppression of the antiviral CD8 T cell response and uncontrolled virus spread, rather than improved CD8 T cell immune surveillance. In Ab-treated wild-type mice, the antiviral CD8 T cell response also collapsed prematurely, and virus clearance was delayed. Additional analysis revealed that, following anti-CD40 treatment, the virus-specific CD8 T cells initially proliferated normally, but an increased cell loss compared with that in untreated mice was observed. The anti-CD40-induced abortion of virus-specific CD8 T cells during LCMV infection was IL-12 independent, but depended partly on Fas expression. Notably, similar anti-CD40 treatment of vesicular stomatitis virus-infected mice resulted in an improved antiviral CD8 T cell response, demonstrating that the effect of anti-CD40 treatment varies with the virus infection studied. For this reason, we recommend further evaluation of the safety of this regimen before being applied to human patients.
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PMID:Agonistic anti-CD40 antibody profoundly suppresses the immune response to infection with lymphocytic choriomeningitis virus. 1723 16

Lentiviral vectors are promising vaccines because they can transduce and express antigens in dendritic cells in vivo, leading to potent immunization. To improve the safety and efficacy of lentivector vaccination, we sought to target vector transduction to antigen-presenting cells by modifying the viral envelope. To do this we screened a nonimmunized human single-chain antibody phage display library for phage that bound mouse bone marrow-derived dendritic cells (BMDCs) and isolated three single-chain antibodies (scFvs) that bound to more than 20% of cells in the BMDC culture. The three scFvs also bound to dendritic cells, macrophages, monocytes, and B cells from mouse spleen, but not to neutrophils, eosinophils, or T cells. Immunoblotting demonstrated that two unique scFvs, C2 and C7, recognized MHC class II. We constructed chimeric envelope proteins, by fusing these two scFvs to the amino terminus of the amphotropic murine leukemia virus envelope (MLV-A). These chimeric envelopes were expressed on the surface of lentiviral vector particles and enhanced infection (5- to 10-fold) of BMDC cultures, compared with lentiviral vectors with unmodified MLV-A envelope. Similarly, the chimeric envelopes enhanced (10- to 20-fold) the infection of primary lymph node class II-positive cells. One of the envelopes, C2, gave increased interferon-gamma production from splenocytes of vaccinated mice compared with MLV-A, achieving a level similar to that obtained with vesicular stomatitis virus glycoprotein G, when used to deliver an ovalbumin model antigen gene. These results demonstrate that surface-targeting lentiviral vector transduction of antigen-presenting cells gives efficient and potentially safer immunization.
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PMID:Single-chain antibodies that target lentiviral vectors to MHC class II on antigen-presenting cells. 1926 Jul 68


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