Cross-Protection against Lethal H5N1 Challenge in Ferrets with an Adjuvanted Pandemic Influenza Vaccine

Background. Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI) of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be produced rapidly and in sufficient quantities. Potential

Potent enhancement of cellular and humoral immune responses against recombinant hepatitis B antigens using AS02A adjuvant in healthy adults

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Characterization of the spontaneous human anti-tumor response

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FcR cross-linking on monocytes results in impaired T cell stimulatory capacity.

Presentation of antigen to T lymphocytes without the appropriate co-stimulatory signals results in a state of antigen-specific unresponsiveness. Despite the presumed importance of the B7-CD28 interaction for the initiation and maintenance of T cell-mediated immune responses, relatively few studies have addressed the regulation of B7 expression. We have studied the expression of the CD80 (B7-1) and B7-2 molecules on peripheral blood monocytes following different activation signals, and it was demonstrated that not only IFN-gamma, but also granulocyte macrophage colony stimulating factor can induce CD80 expression on monocytes. In addition, we found that cross-linking of FcR on monocytes strongly inhibits the up-regulation of CD80 and B7-2, with as a functional consequence that the capacity to function as antigen presenting cells (APC) and to stimulate T cell activation is severely impaired. When cultures were prepared in 96-well plates coated with human IgG, stimulation of T cells with allogeneic monocytes resulted only in modest T cell proliferation and no detectable IL-2 secretion as compared with untreated culture plates or plates coated with Fab fragments of human IgG. Under these conditions cross-linking of CD28 on the T cells with specific mAb completely reverted the inhibitory effect observed after culture on IgG-coated plates. Furthermore, FcR cross-linking on monocytes strongly inhibited the capacity of monocytes to induce a specific memory T cell response to viral, bacterial and fungal antigens, whereas the treatment did not impair the capacity of the T cells to respond to pokeweed mitogen, phytohemagglutinin and concanavalin A. We conclude that after FcR cross-linking, the impaired APC function is most likely due to the inability of monocytes to provide the essential co-stimulatory signals to the T cells via the B7-CD28/CTLA-4 interaction.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

La réponse immune antitumorale, cascade idiotypique et immunotherapy spécifique: mythe ou réalité ?

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Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6 L2E7 vaccine: infection of external anogenital warts with multiple HPV types and failure of therapeutic vaccination

Background.Cellular immunity is involved in spontaneous clearance of anogenital warts caused, most typically, by human papillomavirus (HPV) type 6 or 11, supporting the concept of therapeutic vaccination. A therapeutic vaccine composed of HPV‐6 L2E7 fusion protein and AS02A adjuvant was evaluated in conjunction with conventional therapies in subjects with anogenital warts. Methods.A total of 457 subjects with anogenital warts were screened, of which 320 with HPV‐6 and/or HPV‐11 infection were enrolled into 2 double‐blind, placebo‐controlled substudies. Three doses of vaccine or placebo were administered along with either ablative therapy or podophyllotoxin. Results.Although a positive trend toward clearance was seen in patients infected with only HPV‐6, in neither substudy did the vaccine significantly increase the efficacy of conventional therapies, despite induction of adequate immune responses. Extensive HPV typing by polymerase chain reaction demonstrated that a majority of screened subjects (73.7%) were infected with HPV‐6 and/or HPV‐11 and that a large proportion (40.1%) were infected with multiple HPV types. HPV types that put subjects at high risk of development of cervical cancer were detected in 39.8% of subjects. Conclusions.Infection with multiple HPV types, including high‐risk types, is common in anogenital wart disease. Therapeutic vaccination failed to increase the efficacy of conventional therapies