Stabilized viral class I fusion proteins

1. A stable pre-fusion class I fusion protein, comprising one or more mutations in the hinge-loop that is present between the base helix and the RR1, wherein the one or more mutations comprise a mutation of one or more hydrophobic amino acid residues into Pro, and wherein the class I fusion protein is a filovirus fusion F protein, a retroviral envelope protein, or an influenza hemagglutinin (HA) protein.

2. The fusion protein according to claim 1 , wherein the class I fusion protein is an Ebola virus F protein.

3. The fusion protein according to claim 2 , comprising a mutation in the hinge loop of the amino acid residue Thr at position 577 and/or a mutation of the amino acid residue Leu at position 579.

4. The fusion protein according to claim 1 , wherein the class I fusion protein is an Ebola virus F protein comprising an amino acid sequence selected from the group consisting of:

(SEQ ID NO: 11)

GLICGLRQLANETTQALQLFLRATPELRTFSILNRKAIDFLLQR;

and

(SEQ ID NO: 12)

GLICGLRQLANETTQALQLFLRATTEPRTFSILNRKAIDFLLQR.

5. The fusion protein according to claim 1 , wherein the class I fusion protein is a Marburg virus F protein.

6. The fusion protein according to claim 5 , comprising a mutation in the hinge loop of the amino acid residue Thr at position 578, and/or a mutation of the amino acid residue Glu at position 580.

7. The fusion protein according to claim 5 , wherein the class I fusion protein is a Marburg virus F protein comprising an amino acid sequence selected from the group consisting of:

(SEQ ID NO: 15)

NLVCRLRRLANQTAKSLELLLRVTPEERTFSLINRHAIDFLLAR;

and

(SEQ ID NO: 16)

NLVCRLRRLANQTAKSLELLLRVTTEPRTFSLINRHAIDFLLAR.

8. The fusion protein according to claim 1 , wherein the class I fusion protein is a retroviral HIV-1 envelope protein.

9. The fusion protein according to claim 8 , comprising a mutation in the hinge loop of the amino acid residue Leu at position 555, a mutation of amino acid residue Leu at position 556, and/or a mutation of the amino acid residue Ala at position 558.

10. The fusion protein according to claim 8 , wherein the class I fusion protein is a HIV-1 envelope protein comprising an amino acid sequence selected from the group consisting of:

(SEQ ID NO: 3)

QARQLLSGIVQQQNNPLRAIEAQQHLLQLTVWGIKQLQARI;

(SEQ ID NO: 4)

QARQLLSGIVQQQNNLPRAIEAQQHLLQLTVWGIKQLQARI;

(SEQ ID NO: 5)

QARQLLSGIVQQQNNLLRPIEAQQEILLQLTVWGIKQLQARI;

(SEQ ID NO: 6)

QARQLLSGIVQQQSNPLRAIEAQQHMLQLTVWGIKQLQTRV;

(SEQ ID NO: 7)

QARQLLSGIVQQQSNLPRAIEAQQHMLQLTVWGIKQLQTRV;

and

(SEQ ID NO: 8)

QARQLLSGIVQQQSNLLRPIEAQQHMLQLTVWGIKQLQTRV.

11. The fusion protein according to claim 1 , wherein the class I fusion protein is a retroviral HIV-2 envelope protein.

12. The fusion protein according to claim 11 , comprising a mutation in the hinge loop of the amino acid residue Leu at position 553 and/or a mutation of amino acid residue Leu at position 554, a mutation of amino acid residue Ala at position 556, and/or a mutation of amino acid residue Val at position 557.

13. The fusion protein according to claim 11 , wherein the class I fusion protein is a HIV-2 envelope protein comprising an amino acid sequence selected from the group consisting of:

(SEQ ID NO: 31)

LLAGIVQQQQQPLDAVKRQQELLRLTVWG;

(SEQ ID NO: 32)

LLAGIVQQQQQLPDAVKRQQELLRLTVWG;

(SEQ ID NO: 33)

LLAGIVQQQQQLLDPVKRQQELLRLTVWG;

and

(SEQ ID NO: 34)

LLAGIVQQQQQLLDAPKRQQELLRLTVWG.

14. The fusion protein according to claim 1 , wherein the class I fusion protein is an influenza H1 hemagglutinin (HA) protein.

15. The fusion protein according to claim 14 , comprising a mutation in the hinge loop (B-loop) of HA2 of the amino acid residue Phe at position 63 and/or a mutation of the amino acid residue Leu at position 73.

16. The fusion protein according to claim 14 , wherein the class I fusion protein is an influenza H1 hemagglutinin (HA) protein comprising an amino acid sequence selected from the group consisting of:

(SEQ ID NO: 19)

QKSTQNAINGITNKVNSVIEKMNTQPTAVGKEFNKLERRMENLNKKVDDG

FID;

and

(SEQ ID NO: 20)

QKSTQNAINGITNKVNSVIEKMNTQFTAVGKEFNKPERRMENLNKKVDDG

FID.

17. The fusion protein according to claim 1 , wherein the class I fusion protein is an influenza H3 hemagglutinin (HA) protein.

18. The fusion protein according to claim 17 , comprising a mutation in the hinge loop (B-loop) of HA2 of the amino acid residue Phe at position 72 and/or a mutation of the amino acid residue Val at position 82.

19. The fusion protein according to claim 17 , wherein the class I fusion protein is an influenza H3 hemagglutinin (HA) protein comprising an amino acid sequence selected from the group consisting of:

(SEQ ID NO: 23)

LKSTQAAINQINGKLNRLIGKTNEKPHQIEKEFSEVEGRIQDLEKYVEDT

KID;

and

(SEQ ID NO: 24)

LKSTQAAINQINGKLNRLIGKTNEKFHQIEKEFSEPEGRIQDLEKYVEDT

KID.

20. The fusion protein according to claim 1 , wherein the class I fusion protein is an influenza hemagglutinin (HA) polypeptide of an influenza B virus.

21. The fusion protein according to claim 20 , comprising a mutation in the hinge loop (B-loop) of HA2 of the amino acid residue Leu at position 62 and/or a mutation of the amino acid Leu at position 72.

22. The fusion protein according to claim 20 , wherein the class I fusion protein is an influenza hemagglutinin (HA) polypeptide of an influenza B virus comprising an amino acid sequence selected from the group consisting of:

(SEQ ID NO: 27)

LKSTQEAINKITKNLNSLELEVKNPQRLSGAMDELHNEILELDEKVDDL

RAD;

and

(SEQ ID NO: 28)

LKSTQEAINKITKNLNSLELEVKNLQRLSGAMDEPHNEILELDEKVDDL

RAD.

23. A nucleic acid sequence encoding a protein according to claim 1 .

24. A composition comprising a protein and/or a nucleic acid according to claim 1 .

25. A composition comprising a nucleic acid according to claim 23 .