Toll-like receptor agonist-nanoparticle vaccine adjuvant
Compositions and methods are provided relating to TLR agonist nanoparticle vaccine adjuvant formulations.
1 . A vaccine composition comprising:
a pathogen antigen; and
a plurality of nanoparticles, wherein each nanoparticle comprises:
(i) an adjuvant-polymer conjugate comprising a toll-like receptor 7 (TLR7) agonist conjugated via an ester linkage to a poly(lactic acid), wherein the TLR7 agonist is selected from the group consisting of resiquimod and gardiquimod; and
(ii) a copolymer selected from the group consisting of a poly(ethylene glycol)-b-poly(lactic-co-glycolic acid), a poly(ethylene glycol)-b-poly(lactic acid), and a poly(ethylene glycol)-b-poly(glycolic acid); and
(iii) wherein the nanoparticle is formed by co-precipitation of (i) and (ii).
2 . The vaccine composition of claim 1 , wherein the TLR7 agonist is gardiquimod.
3 . The vaccine composition of claim 1 , wherein the copolymer is poly(ethylene glycol)-b-poly(lactic-co-glycolic acid).
4 . The vaccine composition of claim 2 , wherein the copolymer is poly(ethylene glycol)-b-poly(lactic-co-glycolic acid).
5 . The vaccine composition of claim 1 , wherein the nanoparticles are from about 60 nm to about 85 nm in diameter.
6 . The vaccine composition of claim 1 , wherein the standard deviation of diameter of the nanoparticles is less than about 15 nm.
7 . The vaccine composition of claim 1 , wherein the pathogen antigen is a polypeptide.
8 . The vaccine composition of claim 1 , wherein the pathogen antigen is a virus protein subunit.
9 . The vaccine composition of claim 1 , wherein the pathogen antigen is an inactivated whole virus.
10 . The vaccine composition of claim 1 , wherein the pathogen antigen is a coronaviral or influenza antigen.
11 . The vaccine composition of claim 1 , wherein the pathogen antigen is a SARS-CoV-2 antigen.
12 . The vaccine composition of claim 1 , wherein the plurality of nanoparticles comprises the pathogen antigen, which is co-precipitated with (i) the adjuvant-polymer conjugate and (ii) the copolymer.
13 . The vaccine composition of claim 1 , wherein the pathogen antigen is conjugated to the nanoparticles.
14 . The vaccine composition of claim 1 , wherein the pathogen antigen is not conjugated to the nanoparticles.
15 . The vaccine composition of claim 2 , wherein the adjuvant-polymer conjugate has the following structure:
where n is from 5 to 100.
16 . A method of inducing an antigen-specific immune response in a mammal in need thereof comprising intramuscularly, subcutaneously, or intranasally administering to the mammal an effective amount of the vaccine composition of claim 1 .
17 . A method of inducing an antigen-specific immune response in a mammal in need thereof comprising intramuscularly, subcutaneously, or intranasally administering to the mammal an effective amount of the vaccine composition of claim 15 .