A lentiviral vector-based therapeutic vaccine encoding Ag85B-Rv3425 potently increases resistance to acute tuberculosis infection in mice

Abstract

Few treatment options for multidrug-resistant tuberculosis (TB) and extensively drug-resistant TB call attention to the development of novel therapeutic approaches for TB. Therapeutic vaccines are promising candidates because they can induce antigen-specific cellular immune responses, which play an important role in the elimination of Mycobacterium tuberculosis (MTB). In this study, a novel lentiviral vector therapeutic vaccine for delivering MTB-specific fusion protein Ag85B-Rv3425 was constructed. Results showed that one single-injection of this recombinant lentivirus vaccine could trigger antigen-specific Th1-type immune responses in mice. More importantly, mice with acute infection benefited a lot from a single-dose administration of this vaccine by markedly reduced MTB burdens in lungs and spleens as well as attenuated lesions in lungs compared with untreated mice. These results displayed good prospects of this novel vaccine for the immunotherapy of TB.

Assessment of recombinant plasmid expressing fusion antigen Ag85B-Rv3425 in management of acute tuberculosis infection in mice

“…As our previously reported, fusion protein Ag85B-Rv3425 is proved to be an effective multiple epitopes antigen (11,13). In our study, we found that recombinant plasmid A3-Vec, like lentivirus delivered A3 (11), could induce A3 fusion protein specific antibody IgG response, indicating that it could be expressed in mice and then recognized by immune system.…”

“…As a novel immunotherapy strategy, therapeutic vaccine has been successful for TB control not only in latent TB infection model but also in acute infection model (11,12).…”

“…It has been reported rBCG::Ag85B-Rv3425 vaccine, formed by co-expressing Rv3425 and Ag85B in BCG, provides better protective efficacy against Mtb challenge compared with BCG (15). Recently, it was reported that A3 delivered into mice via lentivirus with one single dose administration confers post-infection resistance to acute TB infection (11).…”

“…pLenti 6.3 plasmid was purchased from Biomiga (San Diego, CA, USA). The cloning of ag85b-rv3425 fusion gene into pLenti6.3 plasmid was our described previously (11). A3 protein were purified as our described previously (13).…”

Preclinical Progress of Subunit and Live Attenuated Mycobacterium tuberculosis Vaccines: A Review following the First in Human Efficacy Trial

“…Lentiviruses are widely used in basic biology and gene therapy due to their efficient gene delivery capabilities [109]. They have also been shown to elicit robust cellular immunity and improve mucosal immunity, making them a potential vector for TB vaccines [97,110]. However, lentivectors retain broad tropism, which could impact their safety.…”