Poliovaccine
AssigneeSecretary of State for Health and Social Care
InventorAndrew Macadam
Life of this patent
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Abstract
The invention provides poliovirus like particles, which comprise stabilised empty poliovirus capsids that retain their native antigenic properties. The invention also provides methods of identifying mutations useful in the production of such poliovirus like particles, methods of producing such poliovirus like particles and the use of such poliovirus like particles in methods of vaccinating against poliovirus.
Claims48
A poliovirus-like particle (VLP) comprising at least one modification relative to the poliovirus particle from which the VLP is derived, wherein said at least one modification stabilises the VLP.
The poliovirus-like particle (VLP) of any one of the preceding claims, which is derived from a wild-type poliovirus or from a vaccine strain.
The poliovirus-like particle (VLP) of any one of the preceding claims, which is derived from a type 1, type 2 or type 3 poliovirus.
The poliovirus-like particle (VLP) of any one of the preceding claims, which comprises at least three modifications relative to the poliovirus particle from which the VLP is derived which stabilise the VLP, wherein there is at least one modification in each of:
- (a) a protomer interface;
- and
- (b) a pentamer interface.
The poliovirus-like particle (VLP) of any one of the preceding claims, which further comprises at least one modification in a pocket domain relative to the poliovirus particle from which the VLP is derived.
The poliovirus-like particle (VLP) of any one of the preceding claims, which is derived from a type 1 poliovirus, wherein:
- (a) the protomer interface comprises a mutation at one or both of residues 3178 and 1248 or residues corresponding thereto;
- and/or
- (b) the pentamer interface comprises a mutation at one or both of residues 2025 and 2057 or residues corresponding thereto;
- wherein optionally said VLP comprises a modification in a pocket domain, and said modification is preferably a mutation at residue 1196 or a residue corresponding thereto.
The poliovirus-like particle (VLP) of any one of the preceding claims, which comprises one or more additional modification within one or more of the pocket domain, the protomer interface and/or the pentamer interface, wherein optionally said one or more additional modification is a modification as defined in Table 1, 2 or 3.
The poliovirus-like particle (VLP) of any one of the preceding claims, which comprises at least one further modification in one or more additional structural domain, wherein optionally said one or more additional modification is a modification as defined in Table 1, 2 or 3.
The poliovirus-like particle (VLP) of any one of the preceding claims, which:
- (a) is derived from a type 1 poliovirus and comprises (i) the mutations Q3178L and H1248P in the protomer interface, (ii) the mutations T2025A and D2057E in the pentamer interface, (iii) the mutation L3119M in the VP2/VP3 interface, and (iv) the mutation R4018G in the internal network, wherein said VLP optionally further comprises the mutation V1196L in the pocket domain;
- (b) is derived from a type 2 poliovirus and comprises (i) the mutations F1134L and Y1 159F in the pocket domain, (ii) the mutation Q3178L in the protomer interface, and (iii) the mutations L3085F and T1041I in the pentamer interface;
- or
- (c) is derived from a type 2 poliovirus and comprises (i) the mutations F1134L and V1183L in the pocket domain, (ii) the mutations Q3178L and V1107I in the protomer interface, (iii) the mutation D2057A in the pentamer interface;
- and (iv) the mutation 1405V in the internal network;
- or
- (d) is derived from a type 3 poliovirus and comprises (i) the mutation F1132L in the pocket domain, (ii) the mutations L2215M and F3091S in the protomer interface, (iii) the mutations L20181 and L3085F in the pentamer interface, (iv) the mutation D2241E in the VP2/VP3 interface, (v) the mutations T4067A, H3019Y and optionally A1054V in the internal network, and (vi) the mutation T1105M in the canyon.
The poliovirus-like particle (VLP) of any one of the preceding claims, which is:
- (a) a type 1 VLP derived from a type 1 poliovirus with (i) a P1 having an amino acid sequence of SEQ ID NO:
- 16 or 17;
- (ii) a VP1 having an amino acid sequence of SEQ ID NO:
- 1, a VP0 having an amino acid sequence of SEQ ID NO:
- 5, and a VP3 having an amino acid sequence of SEQ ID NO:
- 3, (iii) a VP I having an amino acid sequence of SEQ ID NO:
- 1, a VP2 having an amino acid sequence of SEQ ID NO:
- 2, and a VP3 having an amino acid sequence of SEQ ID NO:
- 3 and a VP4 having an amino acid sequence of SEQ ID NO:
- 4;
- and/or (iv) a P1;
- VP1, VP0 and VP3;
- or a VP1, VP2, VP3 and VP4 having an amino acid sequence with at least 90% sequence identity to the amino acid sequences of (i) to (iii);
- (b) a type 2 VLP derived from a type 2 poliovirus with (i) a P1 having an amino acid sequence of SEQ ID NO:
- 18 or 19;
- (ii) a VP1 having an amino acid sequence of SEQ ID NO:
- 6, a VP0 having an amino acid sequence of SEQ ID NO:
- 10, and a VP3 having an amino acid sequence of SEQ ID NO:
- 8, (iii) a VP I having an amino acid sequence of SEQ ID NO:
- 6, a VP2 having an amino acid sequence of SEQ ID NO:
- 7, and a VP3 having an amino acid sequence of SEQ ID NO:
- 8 and a VP4 having an amino acid sequence of SEQ ID NO:
- 9;
- and/or (iv) a P1;
- VP1, VP0 and VP3;
- or a VP1, VP2, VP3 and VP4 having an amino acid sequence with at least 90% sequence identity to the amino acid sequences of (i) to (iii);
- or
- (c) a type 3 VLP derived from a type 3 poliovirus with (i) a P1 having an amino acid sequence of SEQ ID NO:
- 20 or 21;
- (ii) a VP1 having an amino acid sequence of SEQ ID NO:
- 11, a VP0 having an amino acid sequence of SEQ ID NO:
- 15, and a VP3 having an amino acid sequence of SEQ ID NO:
- 13, (iii) a VP1 having an amino acid sequence of SEQ ID NO:
- 11, a VP2 having an amino acid sequence of SEQ ID NO:
- 12, and a VP3 having an amino acid sequence of SEQ ID NO:
- 13 and a VP4 having an amino acid sequence of SEQ ID NO:
- 14;
- and/or (iv) a P1;
- VP1, VP0 and VP3;
- or a VP1, VP2, VP3 and VP4 having an amino acid sequence with at least 90% sequence identity to the amino acid sequences of (i) to (iii).
A method of identifying a modification within a poliovirus capsid which increase the stability of said poliovirus capsid, comprising:
- (a) introducing a destabilising mutation into the capsid of a poliovirus strain;
- (b) growing said poliovirus strain at semi-permissive temperatures;
- and
- (c) screening the resulting polioviruses to identify one or more modification that reverse the effect of the destabilising mutation.
Dependencies are inferred from the claim text.