Vaccines for in vivo expression of nucleic acids and methods of using the same
The present disclosure provides particles for delivering a nucleic acid that encodes an immunogenic peptide in an antigen presenting cell. The disclosed particles can function as a vaccine and can be used to treat or prevent a viral or bacterial infection in a subject by expressing in vivo an immunogenic peptide, thereby stimulating the subject's immune system to attack the virus or bacteria that naturally express the immunogenic peptide.
1. A vaccine comprising: (i) a yeast cell wall particle (YCWP) that is surface-modified with polyethyleneimine (PEI), (ii) a lysosome-evading component attached to the YCWP, and (iii) a deoxyribonucleic acid (DNA) sequence encoding an immunogenic peptide from a virus or bacteria, wherein the nucleic acid is attached to the YCWP via a complex formed between the PEI and the nucleic acid, wherein intradermal administration of the vaccine to a human subject elicits an immunogenic response.
2. The vaccine of claim 1 , wherein the lysosome-evading component is a non-infectious virus.
3. The vaccine of claim 2 , wherein the non-infectious virus is an adenovirus.
4. The vaccine of claim 1 , wherein the lysosome-evading component is a quadrivalent influenza vaccine.
5. The vaccine of claim 1 , wherein the lysosome-evading component is a protein.
6. The vaccine of claim 5 , wherein the protein is a hexon protein, a penton protein, melittin, or LL37.
7. The vaccine of claim 1 , wherein the nucleic acid encoding the immunogenic peptide is comprised within an expression vector or plasmid.
8. The vaccine of claim 1 , wherein the immunogenic peptide is derived from a virus or bacteria.
9. The vaccine of claim 1 , wherein the immunogenic peptide is a viral spike protein or an immunogenic fragment thereof.
10. The vaccine of claim 1 , wherein the immunogenic peptide comprises SEQ ID NO: 1 or an immunogenic fragment thereof.
11. The vaccine of claim 1 , wherein the lysosome-evading component is attached to the base particle by an antibody.
12. The vaccine of claim 11 , wherein the lysosome-evading component is an adenovirus and the antibody is an anti-hexon protein antibody.
13. The vaccine of claim 1 , wherein the base particle is a succinimidyl 3-(2-pyridyldithio)propionate (SPDP)-modified YCWP.
14. The vaccine of claim 13 , wherein melittin or LL37 are crosslinked to the YCWP by the SPDP.
15. The vaccine of claim 1 , wherein the vaccine particle is a size that allows it to be phagocytized by a monocytic cell.
16. The vaccine of claim 15 , wherein the monocytic cell is an antigen presenting cell.