Hybrid and tandem expression of
View Patent ↗Two or more Neisserial proteins are joined such that they are translated as a single polypeptide chain. Hybrid proteins are represented by the formula NH 2 -A-[-X-L-] n -B—COOH where X is an amino acid sequence, L is an optional linker amino acid sequence, A is an optional N-terminal amino acid sequence, B is an optional C-terminal amino acid sequence, and n is an integer greater than I. Proteins where each of the n-X— moieties shares sequence identity to each other —X— moiety, the protein is a ‘tandem protein’.
1. A composition comprising a first hybrid protein having formula:
NH 2 -A-[-X-L-] n -B—COOH
wherein L is an optional linker amino acid sequence, A is an optional N-terminal amino acid sequence, B is an optional C-terminal amino acid sequence, and n is an integer greater than 1 and
(a) an X 1 comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 41; and
(b) an X 2 comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 42, mixed with a second hybrid protein having the formula:
NH 2 -A-Y 1 -L-Y 2 —B—COOH
wherein
(c) Y 1 comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 43; and
(d) Y 2 comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 44.
2. The composition of claim 1 wherein n=2.
3. The composition of claim 1 , wherein L has 20 or fewer amino acids.
4. The composition of claim 1 , wherein L is a poly-glycine linker.
5. The composition of claim 4 , wherein the poly-glycine linker is GSGGGG (SEQ ID NO: 27).
6. The composition of claim 1 , wherein A has 40 or fewer amino acids.
7. The composition of claim 1 , wherein B has 40 or fewer amino acids.
8. The composition of claim 1 further comprising a pharmaceutically acceptable carrier.
9. A method of raising an immune response against Neisseria meningitidis serogroup B bacteria in a subject comprising administering to the subject an effective amount of the composition of claim 1 .