Method for Removing Immunosuppressive Properties of HIV Envelope Glycoproteins
AssigneeSkau Aps
InventorsShervin Bahrami, Mogens Ryttergaard Duch
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Abstract
The present invention concerns a method for removal of immunosuppressive effects of envelope glycoproteins derived from human immunodeficiency virus, such as for vaccination purposes and for generation of neutralizing antibodies to HIV. The invention further concerns vaccines and antibodies obtainable by the method, as well as the use of such vaccines and antibodies.
Claims24
-75. (canceled)
A method for making an HIV-1 envelope glycoprotein, said method comprising the steps of:
- selecting at least one HIV envelope glycoprotein from the group consisting of GP41 and GP160;
- and
- modifying the immunosuppressive domain of said envelope glycoprotein, said immunosuppressive domain being localizable by the sequence:
- LX2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17X18X19X20X21GCX24X25X26X27X28C
- (SEQ ID NO:1), wherein X2-X21 and X24-X28 are independently any amino acid residue;
- said modifying step comprising mutating or genetically modifying at least one amino acid selected from the group consisting of amino acids X2-X17, wherein said amino acids after said modifying step are selected from the following respective groups:
- X2:
- Q, R, N, A, G
- X3:
- A, T, V, G, Q, R
- X4:
- R, K, G, A, Q
- X5:
- V, I, L, M, A, G, Q, R
- X6:
- L, A, C, D, E, F, G, H, I, K, M, N, P, Q, R, S, T, V, W, Y
- X7:
- A, T, S, G, Q, R
- X8:
- V, I, L, Q, M, A, G, Q, R
- X9:
- E, K, A, G, Q, R
- X10:
- R, S, T, K, G, N, E, D, A, G, Q
- X11:
- L, A, C, D, E, F, G, H, I, K, M, N, P, Q, R, S, T, V, W, Y
- X12:
- L, V, I, M, R, A, G, Q
- X13:
- K, Q, R, A, E, G, S, H, W, T, V
- X14:
- D, E, N, H, G, A, G, Q, R
- X15:
- Q, R, A, G
- X16:
- Q, A, S, K, T, R, H, G
- X17:
- L, M, S, Q, R, H, I, V, F, A, G;
- wherein said glycoprotein is capable of being expressed on the surface of a cell, virus, or virus-like particle and provides reduced immune suppression, allowing said HIV-1 envelope glycoprotein to generate an enhanced immune response as compared to the corresponding wild-type HIV-1 envelope glycoprotein.
An antigen comprising the amino acid sequence:
- LX2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17
- wherein X2-X17 are independently selected from the following amino acids:
- X2:
- Q, R, N, A, G
- X3:
- A, T, V, G, Q, R
- X4:
- R, K, G, A, Q
- X5:
- V, I, L, M, A, G, Q, R
- X6:
- L, A, C, D, E, F, G, H, I, K, M, N, P, Q, R, S, T, V, W, Y
- X7:
- A, T, S, G, Q, R
- X8:
- V, I, L, Q, M, A, G, Q, R
- X9:
- E, K, A, G, Q, R
- X10:
- R, S, T, K, G, N, E, D, A, A, G, Q
- X11:
- L, A, C, D, E, F, G, H, I, K, M, N, P, Q, R, S, T, V, W, Y
- X12:
- L, V, I, M, R, A, G, Q
- X13:
- K, Q, R, A, E, G, S, H, W, T, V
- X14:
- D, E, N, H, G, A, G, Q, R
- X15:
- Q, R, A, G
- X16:
- Q, A, S, K, T, R, H, G
- X17:
- L, M, S, Q, R, H, I, V, F, A
- subject to the proviso that said sequence provides the ability of said antigen to be expressed on the surface of a cell, virus, or virus-like particle, and said antigen is capable of generating an immune response.
A vaccine composition for HIV comprising an HIV-1 envelope glycoprotein obtainable according to the method of claim 1.
Dependencies are inferred from the claim text.