Institut Pasteur

Institut National De La Sante Et De La Recherche Medicale

Assistance Publique-hopitaux De Paris

François Lemonnier

Pierre Langlade-Demoyen

Hüseyin Firat

Sylvain Cardinaud

Claude Auriault

Yu-Chun Lone

Anthony Pajot

André Habel

Marie-Louise Michel

Andreas Suhrbier

Pierre Langlade-Demoyan

Etienne Vilmer

Pierre Rohrlich

Patricia Yotnda

Veronique Pancre

Véronique Pancre

Langlade-Demoyen Pierre

Patricia c/o Institut Pasteur Yotnda

The present invention relates to transgenic mice and isolated transgenic mouse cells, the mice and mouse cells comprising a disrupted H2 class I gene, a disrupted H2 class II gene, a functional HLA class I transgene, and a functional HLA class II transgene. In embodiments, the transgenic mouse or mouse cells are deficient for both H2 class I and class II molecules, wherein the transgenic mouse comprises a functional HLA class I transgene and a functional HLA class II transgene. In embodiments, the transgenic mouse or mouse cell has the genotype HLA-A2HLA-DR1&#x3b2;2m&#xb0;IA&#x3b2;&#xb0;. The invention also relates to methods of using a transgenic mouse of the invention.

Transgenic mice having a human major histocompatibility complex (MHC) phenotype, experimental uses and applications

The invention concerns the optimization of the wild R9M peptide and the use of the resulting peptides for therapeutic vaccination and/or preventive vaccination against leukaemia in humans. More particularly, the invention concerns mutated immunogenic peptides derived from the human TEL/AML1 fusion protein comprising the wild R9M peptide sequence Arg-Ile-Ala-Glu-Czs-Ile-Leu-Gly-Met. The invention also concerns polynucleotides coding for the mutated R9M immunogenic peptides, cellular expression vectors comprising nucleic acid sequences expressing the mutated R9M immunogenic peptides and polyclonal or monoclonal antibodies capable of being fixed on at least one of said peptides/polynucleotides. The invention further concerns the use of said peptides, polynucleotides and/or antibodies for preparing vaccines, anti-tumoral medicines and compositions and for in vitro and in vivo stimulation of the immune response in humans.

Mutated immunogenic peptides derived from R9M, polynucleotides coding for same and therapeutic uses thereof

Transgenic mice having a human major histocompatability complex (MHC) phenotype, experimental uses and applications

The invention relates to the identification and the selection of CTL epitopes able to induce a protection against an HIV infection. More particularly, the invention is concerned with peptides and nucleic acid sequence coding for these peptides derived from HIV-1 proteins such as GAG, POL, ENV, VIF, TAT, VPU, REV and their applications. Preferably the immunogenic peptides are selected from the group consisting of SEQ ID NOs:1 to 18 and functional derivatives thereof. The invention also relates to antibodies directed against said peptides.

Identification of new CD8 epitopes from HIV-1 proteins

H-2 class I negative, HLA-A2.1 transgeniic HHD mice were used for a comparative evaluation of the immunogenicity of HLA-A2.1 restricted human tumor-associated CTL epitopes. A hierarchy was established among these epitopic peptides injected into mice in IFA which correlates globally with their capacity to bind and stabilize HLA-A2.1 molecules. Co-injection of a helper peptide enhanced most CTL responses. In contrast, classical HLA class I transgenic mice which still express their own class I molecules did not, in most cases, develop H.A.-A2.1-restricted CTL responses under the same experimental conditions. Different monoepitopic immunization strategies of acceptable clinical usage were compared in HHD mice. Recombinant Ty-virus-like particles, or DNA encoding epitopes fused to the hepatitis B virus middle envelope protein gave the best results. Using this latter approach and a melanoma-based polyepitope construct, CTL responses against five distinct epitopes could be elicited simultaneously in a single animal. Thus, HHD mice provide a versatile animal model for preclinical evaluation of peptide-based cancer immunotherapy.

Hybrid or chimeric polynucleotides, proteins, and compositions comprising hepatitis B virus sequences

CD8 epitope from HIV-1 protein Vpu

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Bourg la Reine, France

François Lemonnier