Stable poliovirus variants and uses thereof
AssigneeUniversity of Florida Research Foundation, Inc.
InventorsJames B. Flanegan, Robert McKenna, Christopher Daniel Boone, Sushma Abraham Ogram, Barbara Joan Morasco
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Abstract
Provided herein are compositions of virus like particles (VLPs) of poliovirus (PV) that have one or more stabilizing mutations that confer a higher degree of thermostability to the N-antigenic form of the VLPs. These VLPs are non-infectious, and thus safer for use in vaccine development and administration to clinical subjects.
Claims31
A composition comprising poliovirus (PV) virus like particles (VLPs) comprising one or more stabilizing mutations, wherein the VLPs are thermostable in N-antigenic form.
The composition of any one of the preceding claims, wherein the VLPs sediment at 74S on a 15-30% sucrose gradient.
The composition of any one of the preceding claims, wherein the VLPs are 28-32 nm in diameter.
The composition of any one of the preceding claims, wherein the VLPs are at a titer of 1-10 N-antigenic units/μl.
The composition of any one of the preceding claims, wherein the VLPs are at a titer of 0.1-100 N-antigenic units/μl.
The composition of any one of the preceding claims, wherein the one or more stabilizing mutations are at positions selected from the list consisting of:
- VP3(178Q), VP3(167V), VP3(4V), VP1(147N), VP1(231A), and VP2(201R).
The composition of any one of the preceding claims, wherein the one or more stabilizing mutations are selected from the list consisting of:
- VP3(178Q.L), VP3(167V.D), VP3(4V.C), VP1(147N.C), VP1(231A.V), and VP2(201R.K).
The composition of any one of the preceding claims, wherein the one or more stabilizing mutations are at the interface between one or more VP proteins in the VLP.
The composition of any one of the preceding claims, wherein the one or more stabilizing mutations are at positions 1-10 amino acids upstream of VP3(178Q), or 1-10 amino acids downstream of VP3(178Q).
The composition of any one of the preceding claims, wherein the one more stabilizing mutations are at positions of VP3 that interface with VP1.
The composition of any one of the preceding claims, wherein the VLPs are thermostable in N-antigenic form for up to 8 h at 37° C.
The composition of any one of the preceding claims, wherein the VLPs are thermostable in N-antigenic form for up to 48 h at 37° C.
The composition of any one of the preceding claims, wherein the VLPs are thermostable in N-antigenic form for up to 5 days at 37° C.
The composition of any one of the preceding claims, wherein the VLPs are thermostable in N-antigenic form for up to 8 h at 39° C.
The composition of any one of the preceding claims, wherein the VLPs are thermostable in N-antigenic form for up to 48 h at 39° C.
The composition of any one of the preceding claims, wherein the VLPs are thermostable in N-antigenic form for up to 5 days at 39° C.
A poliovirus vaccine comprising the composition of any one of the preceding claims.
Dependencies are inferred from the claim text.