Anti-mycobacterial vaccines
Provided herein are genetically modified arenaviruses suitable as vaccines against mycobacterial infections. The invention also relates to pharmaceutical compositions and methods for the prevention and treatment of mycobacterial infections. Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of preventing and treating infections in Mycobacterium tuberculosis.
1. An infectious, replication-deficient arenavirus particle comprising a nucleotide sequence encoding a mycobacterial antigen, wherein the mycobacterial antigen is a fusion protein comprising Ag85B or an antigenic fragment thereof and TB10.4 or an antigenic fragment thereof wherein the mycobacterial antigen is fused to a signal peptide of a tissue plasminogen activator, and wherein the signal peptide of a tissue plasminogen activator comprises the amino acid sequence of SEQ ID NO:7.
2. An infectious, replication-deficient arenavirus particle comprising a nucleotide sequence encoding a mycobacterial antigen, wherein the mycobacterial antigen is a fusion protein comprising Ag85B or an antigenic fragment thereof and TB10.4 or an antigenic fragment thereof wherein the mycobacterial antigen is fused to a signal peptide of a tissue plasminogen activator, and wherein the infectious, replication-deficient arenavirus particle comprises a genomic segment, wherein the genomic segment comprises a nucleotide sequence that is at least 98%, 99%, or 100% identical to SEQ ID NO:1.
3. An isolated nucleic acid, wherein the isolated nucleic acid encodes an arenavirus genomic segment of an arenavirus, wherein one open reading frame of the genomic segment is deleted or functionally inactivated, wherein the genomic segment encodes a mycobacterial antigen, wherein the mycobacterial antigen is a fusion protein comprising Ag85B or an antigenic fragment thereof and TB10.4 or an antigenic fragment thereof, and wherein the mycobacterial antigen is fused to a signal peptide of a tissue plasminogen activator, and wherein the isolated nucleic acid comprises a nucleotide sequence that is at least 98%, 99%, or 100% identical to SEQ ID NO:1.