Tuberculosis (primarily pulmonary) is the leading cause of death and disability from infectious diseases worldwide (excluding the COVID-19 period), killing 1.2 million people annually. The burden of TB is particularly high in low- and middle-income countries. TB is the leading cause of morbidity and mortality across all diseases in these countries, and has remained largely unchanged in recent decades.
TB, caused by infection with Mycobacterium tuberculosis, carries a high global burden, partly due to the lack of a sufficiently effective TB vaccine. The only licensed TB vaccine, Bacillus Calmette-Guérin (BCG), is highly effective in preventing TB in children, but its effectiveness decreases significantly in adolescents and adults. Furthermore, repeated BCG vaccinations have been ineffective.
Therefore, developing more effective TB vaccines is a global health priority. Furthermore, given the high rates of early childhood BCG vaccination in TB-endemic countries, the next generation of TB vaccines may need to be administered in conjunction with BCG immunization.
In September 2025, researchers from Harvard Medical School published a research paper titled "Mining the CD4 Antigen Repertoire for Next-Generation Tuberculosis Vaccines" in the leading international academic journal Cell. By mining the human CD4 T cell antigen repertoire, the study developed a trivalent mRNA-LNP vaccine that enhanced and surpassed the protective efficacy of BCG in a mouse model. This research provides new insights into the biological properties of potential tuberculosis vaccine antigens and points the way forward for the development of next-generation tuberculosis vaccines.
| Cat.No. | Product Name | Price |
|---|---|---|
| PMCRL-0016 | Sox2 circRNA-LNP | Inquiry |
| PMCRL-0017 | Oct4 circRNA-LNP | Inquiry |
| PMCRL-0018 | Klf circRNA-LNP | Inquiry |
| PMCRL-0019 | c-Myc circRNA-LNP | Inquiry |
| PMCRL-0020 | Lin28 circRNA-LNP | Inquiry |
| PMmRNL-0001 | EGFP mRNA-LNP | Inquiry |
| PMmRNL-0002 | mCherry mRNA-LNP | Inquiry |
| PMmRNL-0003 | Firefly Luciferase mRNA-LNP | Inquiry |
| PMmRNL-0004 | Cas9-HA mRNA-LNP | Inquiry |
| PMmRNL-0005 | EGFP mRNA (no modificaiton)-LNP | Inquiry |
| PMmRNL-0006 | mCherry mRNA (no modificaiton)-LNP | Inquiry |
| PMmRNL-0007 | Firefly Luciferase mRNA (no modificaiton)-LNP | Inquiry |
| PMmRNL-0008 | spCas9 mRNA (no modificaiton)-LNP | Inquiry |
| PMmRNL-0009 | spCas9 mRNA (N1-Me-Pseudo UTP modified)-LNP | Inquiry |
| PMmRNL-0010 | SARS COV-2 Spike Protein (Alpha Variant) mRNA-LNP | Inquiry |
Tuberculosis is the leading cause of death from infectious diseases worldwide. Bacillus Calmette-Guérin (BCG) was developed and first used in humans in 1921. Over 100 years later, BCG remains the only clinically approved TB vaccine.
A persistent challenge in TB vaccine development is systematically selecting antigens from a large pool of potential candidate antigens. CD4 T cells are the primary adaptive immune cells mediating control of Mycobacterium tuberculosis, with CD8 T cells and other lymphocyte subsets also likely playing a role. Latent TB, a clinical state following exposure to Mycobacterium tuberculosis characterized by adaptive immune control, may be dependent on CD4 T cell responses. The research team utilized a genome-wide dataset of CD4 T cell responses in patients with latent TB and developed a process for systematically screening vaccine antigens for protective efficacy in mice. This approach enabled them to screen human CD4 T cell target antigens in mice for potency, identifying a series of TB antigens with varying protective efficacy, most of which are not currently in clinical development. The research team observed immune cross-reactivity between phylogenetically clustered antigens, reflecting shared CD4 epitopes.
Figure 1. An antigen screen ranks protective CD4 T cell antigens and yields a novel trivalent mRNA vaccine that protects against TB challenges in mice. (Vidal S J, et al., 2025)
Based on these findings, the team developed a trivalent mRNA vaccine composed of PPE20 (Rv1387), EsxG (Rv0287), and PE18 (Rv1788), which enhanced and exceeded the protective efficacy of BCG in multiple mouse models. Finally, the team observed that 84% of individuals exposed to Mycobacterium tuberculosis developed cellular immune responses to these antigens, suggesting that this mRNA vaccine may also be effective in humans. These data advance our understanding of tuberculosis vaccine immunology and provide a path forward for the development of next-generation tuberculosis vaccines.
The team plans to conduct a Phase 1 clinical trial to test the safety and efficacy of this mRNA vaccine in humans, thereby providing a new avenue for preventing tuberculosis, one of the world's most cunning infectious diseases.
Reference
Vidal S J, et al. Mining the CD4 antigen repertoire for next-generation tuberculosis vaccines. Cell, 2025.