Respiratory syncytial virus (RSV) polyanhydride nanoparticle vaccine
Disclosed are compositions and methods for vaccinating susceptible individuals against infection by respiratory syncytial virus (RSV). The disclosed compositions include vaccine compositions comprising an effective amount of respiratory syncytial virus (RSV) F protein in a pre-fusion stabilized form and/or M protein incorporated into biodegradable polyanhydride polymer particles for inducing an immune response against RSV. The vaccine compositions also may include a suitable adjuvant.
1 . A vaccine composition comprising
a) an effective amount of respiratory syncytial virus (RSV) F protein in a pre-fusion stabilized form and RSV M protein,
b) a CpG oligonucleotide, and
c) biodegradable polyanhydride polymer particles formed from a 1,ω-bis(p-carboxyphenoxy)(C 2 -C 12 )alkane, a 1,ω-bis(p-carboxyphenoxy)(C 2 -C 12 )dioxa-alkane, and a (C 5 -C 20 )alkanoic diacid,
wherein the pre-fusion stabilized RSV F protein and RSV M protein, and the CpG oligonucleotide are incorporated into the biodegradable polyanhydride polymer particles for inducing an immune response against RSV.
2 . The vaccine composition of claim 1 , wherein the F protein in a pre-fusion stabilized form is selected from the group consisting of DS-Cav1, DS-TriC, Vav-1-TriC, DX-Cav1-TriC, Pre-F-GCN4t, SC-DM, and SC-TM.
3 . The vaccine composition of claim 2 , wherein the F protein in a pre-fusion stabilized form is DS-Cav1.
4 . The vaccine composition of claim 1 , wherein the CpG oligonucleotide is a CpG oligodeoxynucleotide (ODN).
5 . The vaccine composition of claim 1 , wherein the vaccine composition induces an antibody response and a CD4 T cell response when administered to a subject in need thereof.
6 . The vaccine composition of claim 1 , wherein the polymer is formed from 1,6-bis(p-carboxyphenoxy)hexane (CPH), 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctance (CPTEG), and sebacic acid (SA).
7 . The vaccine composition of claim 6 , wherein the CPH and CPTEG are at a ratio range of CPH:CPTEG of 80-60:20-40.
8 . The vaccine composition of claim 1 , further comprising an RSV protein selected from NS1, NS2, N, P, SH, G, M2-1, M2-2, L, or any combinations thereof.
9 . A method comprising administering the vaccine composition of claim 1 at least once to a subject who is at risk for infection by RSV.
10 . The method of claim 9 , wherein after the vaccine composition is administered to the subject, the subject is protected against infection by RSV.
11 . The method of claim 9 , wherein the vaccine composition is administered by a route selected from intranasal, pulmonary, oral, subcutaneous, intramuscular, or intravenous.
12 . The method of claim 9 , wherein the vaccine composition reduces RSV replication in the subject.
13 . The method of claim 9 , comprising administering the vaccine composition to the subject a second time after the first administration of the vaccine.
14 . The method of claim 13 , wherein the subject is protected against infection by RSV and the protection is effective upon exposure to RSV.
15 . The method of claim 13 , wherein the vaccine composition reduces RSV replication in the subject.
16 . The method of claim 14 , wherein the vaccine composition induces CD4 T cells, CD8 T cells, and B cells in the subject.
17 . The method of claim 14 , wherein the vaccine composition induces long-term immunity to RSV infection.
18 . A method comprising administering a vaccine composition to a subject who is at risk for infection by RSV, the vaccine composition comprising:
a) an effective amount of respiratory syncytial virus (RSV) F protein in a pre-fusion stabilized form,
b) a CpG oligonucleotide, and
c) biodegradable polvanhydride polymer particle formed from a 1,ω-bis(p-carboxyphenoxy)(C 2 -C 12 )alkane, a 1,ω-bis(p-carboxyphenoxy)(C 2 -C 12 )dioxa-alkane, and a (C 5 -C 20 )alkanoic diacid,
wherein the pre-fusion stabilized RSV F protein and the CpG oligonucleotide are incorporated into the biodegradable polyanhydride polymer particles, wherein the vaccine composition is administered at least once to the subject, and wherein administration of the vaccine composition induces an immune response against RSV in the subject that protects against infection by RSV and the protection is effective upon exposure to RSV.
19 . The method of claim 18 , wherein the vaccine composition induces CD4 T cells, CD8 T cells, and B cells in the subject.
20 . The method of claim 18 , wherein the vaccine composition induces long-term immunity to RSV infection.