Abstract: The present disclosure is directed to oral vaccine dosage forms and processes for producing the oral vaccine dosage forms. The dosage forms include lipid-based vesicles (e.g., virosomes, liposomes) harboring an immunogenic amount of at least one vaccinal target molecule, with or without adjuvant. Specifically, Applicants discovered a combination of the composition of the liquid virosome concentrates, the composition of the base matrix for the solid dosage form formulation (excluding the virosome concentrate), and the manufacturing conditions for the dosage forms that can produce a freeze dried sublingual dosage form having physical robustness, particle and antigen integrity and stability.

Abstract: The present disclosure is directed to oral vaccine dosage forms and processes for producing the oral vaccine dosage forms. The dosage forms include lipid-based vesicles (e.g., virosomes, liposomes) harboring an immunogenic amount of at least one vaccinal target molecule, with or without adjuvant. Specifically, Applicants discovered a combination of the composition of the liquid virosome concentrates, the composition of the base matrix for the solid dosage form formulation (excluding the virosome concentrate), and the manufacturing conditions for the dosage forms that can produce a freeze dried sublingual dosage form having physical robustness, particle and antigen integrity and stability.

Abstract: The present disclosure is directed to oral vaccine dosage forms and processes for producing the oral vaccine dosage forms. The dosage forms include lipid-based vesicles (e.g., virosomes, liposomes) harboring an immunogenic amount of at least one vaccinal target molecule, with or without adjuvant. Specifically, Applicants discovered a combination of the composition of the liquid virosome concentrates, the composition of the base matrix for the solid dosage form formulation (excluding the virosome concentrate), and the manufacturing conditions for the dosage forms that can produce a freeze dried sublingual dosage form having physical robustness, particle and antigen integrity and stability.

Abstract: The present disclosure is directed to oral vaccine dosage forms and processes for producing the oral vaccine dosage forms. The dosage forms include lipid-based vesicles (e.g., virosomes, liposomes) harboring an immunogenic amount of at least one vaccinal target molecule, with or without adjuvant. Specifically, Applicants discovered a combination of the composition of the liquid virosome concentrates, the composition of the base matrix for the solid dosage form formulation (excluding the virosome concentrate), and the manufacturing conditions for the dosage forms that can produce a freeze dried sublingual dosage form having physical robustness, particle and antigen integrity and stability.

Abstract: The present invention relates to a virosome-like vesicle comprising at least a gp41-derived antigen or an analogue thereof, said gp41-derived antigen being located to the external surface of and/or encapsulated inside said vesicle and being in a convenient configuration for conferring said virosome-like vesicle with an ability to induce an immune response against a gp41 protein or a human immunodeficiency virus (HIV).

Abstract: The present invention deals with a modified polypeptide comprising three contiguous segments N, L and C represented by the formula N-L-C and comprising: a N-helix region of gp41 (N), a C-helix region of gp41 (C), and a connecting loop comprising a synthetic linker (L) between the N and C-helices, the linker replacing amino acids 593-617 of gp41, the numbering scheme being based upon the prototypic isolate HIV-1 HxB2 Clade B strain, said polypeptide comprising the calveolin-1 neutralizing and 98.6 D epitopes, but not 2F5 and 4E10 epitopes, not the fusion peptide, the polypeptide having a minimal immunogenic cross-reactivity with human interleukin 2 (IL2).

Abstract: The present invention deals with a method for therapeutic or prophylactic treatment of HIV, in particular a prophylactic vaccinal method, comprising at least: administering to a patient a first antigen comprising the broadly neutralizing epitopes of the Membrane Proximal Ectodomain Region (MPER) of gp41, and administering to the same patient a second antigen comprising a modified polypeptide comprising three contiguous segments N, L and C represented by the formula N-L-C and comprising: a N-helix region of gp41(N), a C-helix region of gp41(C), and a connecting loop comprising a synthetic linker (L) between the N and C-helices, the linker replacing amino acids 593-617 of gp41, the numbering scheme being based upon the prototypic isolate HIV-1 HxB2 Clade B strain, said polypeptide comprising the calveolin-1 neutralizing and 98.6 D epitopes, but not 2F5 and 4E10 epitopes, not the fusion peptide, the polypeptide having a minimal immunogenic cross-reactivity with human interleukin 2.

Abstract: The present invention deals with a method for therapeutic or prophylactic treatment of HIV, in particular a prophylactic vaccinal method, comprising at least: administering to a patient a first antigen comprising the broadly neutralizing epitopes of the Membrane Proximal Ectodomain Region (MPER) of gp41, and administering to the same patient a second antigen comprising a modified polypeptide comprising three contiguous segments N, L and C represented by the formula N-L-C and comprising: a N-helix region of gp41(N), a C-helix region of gp41(C), and a connecting loop comprising a synthetic linker (L) between the N and C-helices, the linker replacing amino acids 593-617 of gp41, the numbering scheme being based upon the prototypic isolate HIV-1 HxB2 Clade B strain, said polypeptide comprising the calveolin-1 neutralizing and 98.6 D epitopes, but not 2F5 and 4E10 epitopes, not the fusion peptide, the polypeptide having a minimal immunogenic cross-reactivity with human interleukin 2.

Abstract: The present invention deals with a modified polypeptide comprising three contiguous segments N, L and C represented by the formula N?L?C and comprising: a N-helix region of gp41 (N), a C-helix region of gp41 (C), and a connecting loop comprising a synthetic linker (L) between the N and C-helices, the linker replacing amino acids 593-617 of gp41, the numbering scheme being based upon the prototypic isolate HIV-1 HxB2 Clade B strain, said polypeptide comprising the calveolin-1 neutral izing and 98.6 D epitopes, but not 2F5 and 4E10 epitopes, not the fusion peptide, the polypeptide having a minimal immunogenic cross-reactivity with human interleukin 2 (IL2).

Abstract: The present invention concerns a modified polypeptide containing at least an immunodominant region and the connecting loop between N- and C-helices of gp41 ectodomain of HIV-1, wherein the connecting loop includes at least a linker fragment having: —a size convenient for keeping the native conformation of the interaction between N- and C-helices, and —an hydrophily sufficient to provide a soluble and stable trimeric form to said modified polypeptide.

Abstract: The present invention relates to methods for synthesizing conformationally constrained peptides and cyclic peptidomimetics obtainable by these methods which are conformationally constrained due an internal cross-link. This cross-link is formed between the side chain of an amino acid residue or analog and a (2S, 4S)4-functionalized proline residue. The invention further relates to the use of (2S, 4S)-4-functionalized proline residues as building units in the synthesis of such peptidomimetics and to the use thereof as antigens, alone or in combination with suitable immunopotentiating delivery systems, for example immunopotentiating reconstituted influenza virosomes to elicit an immune response in a mammal. Moreover, the invention also relates to pharmaceutical compositions containing the same.

Abstract: The present invention relates to methods for synthesizing conformationally constrained peptides and cyclic peptidomimetics obtainable by these methods which are conformationally constrained due an internal cross-link. This cross-link is formed between the side chain of an amino acid residue or analog and a (2S, 4S)4-functionalized proline residue. The invention further relates to the use of (2S, 4S)-4-functionalized proline residues as building units in the synthesis of such peptidomimetics and to the use thereof as antigens, alone or in combination with suitable immunopotentiating delivery systems, for example immunopotentiating reconstituted influenza virosomes to elicit an immune response in a mammal. Moreover, the invention also relates to pharmaceutical compositions containing the same.

Abstract: The invention relates to a monoclonal antibody or a fragment thereof comprising in the H chain variable region at least one complementarity determining region (CDR) selected among CDR1, CDR2 and CDR3 having, respectively, an amino acids sequence set forth as SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 3 or functional analogues thereof.

Abstract: The present invention relates to a virosome-like vesicle comprising at least a gp41-derived antigen or an analogue thereof, said gp41-derived antigen being located to the external surface of and/or encapsulated inside said vesicle and being in a convenient configuration for conferring said virosome-like vesicle with an ability to induce an immune response against a gp41 protein or a human immunodeficiency virus (HIV).

Abstract: The present invention relates to methods for synthesizing conformationally constrained peptides and cyclic peptidomimetics obtainable by these methods which are conformationally constrained due an internal cross-link. This cross-link is formed between the side chain of an amino acid residue or analog and a (2S, 4S)4-functionalized proline residue. The invention further relates to the use of (2S, 4S)-4-functionalized proline residues as building units in the synthesis of such peptidomimetics and to the use thereof as antigens, alone or in combination with suitable immunopotentiating delivery systems, for example immunopotentiating reconstituted influenza virosomes to elicit an immune response in a mammal. Moreover, the invention also relates to pharmaceutical compositions containing the same.

Abstract: The present invention concerns a modified polypeptide containing at least an immunodominant region and the connecting loop between N- and C-helices of gp41 ectodomain of HIV-1, wherein the connecting loop includes at least a linker fragment having: —a size convenient for keeping the native conformation of the interaction between N- and C-helices, and—an hydrophily sufficient to provide a soluble and stable trimeric form to said modified polypeptide.