Tuberculosis (TB) remains a serious public health threat around the world. An effective vaccine is urgently required for cost-effective, long-term control of TB. However, the only licensed vaccine Bacillus Calmette-Guerin (BCG) is limited to prevent TB for its highly variable efficacy. Substantial progress has been made in research and development (R&D) of TB vaccines in the past decades, and a dozen vaccine candidates, including live attenuated mycobacterial vaccines, killed mycobacterial vaccines, adjuvanted subunit vaccines, viral vector vaccines, and messenger RNA (mRNA) vaccines were developed in clinical trials to date. Nevertheless, many challenges to the successful authorization for the use and deployment of an effective tuberculosis vaccine remain. Therefore, it is still necessary and urgent to continue exploring new vaccine construction approaches. Virus-like particles (VLPs) present excellent prospects in the field of vaccine development because of their helpful immunological features such as being safe templates without containing viral nucleic acid, repetitive surface geometry, conformational epitopes similar to natural viruses, and enhancing both innate and adaptive immune responses. The marketization process of VLP vaccines has never stopped despite VLP vaccines face several shortcomings such as their complex and slow development process and high production cost, and several VLP-based vaccines, including vaccines against Human papillomavirus (HPV), Hepatitis B Virus (HBV) and malaria, are successfully licensed for use at the market. In this review, we provide an update on the current progress regarding the development of TB vaccines in clinical trials and seek to give an overview of VLP-based TB vaccine candidates.

The challenges posed by Mycobacterium tuberculosis infection require the gradual removal of the pool of latent tuberculosis infection (LTBI). The current cell-immune-based diagnostic tests used to identify LTBI individuals have several irreversible drawbacks. In the present study, we attempted to identify novel diagnostic antigens for LTBI. A high-throughput glutathione S-transferase (GST)-fusion technology was used to express over 409 TB proteins and sera from LTBI and healthy individuals was used to interrogate these GST-TB fusion proteins. Of 409 TB proteins, sixty-three reacted seropositive and defined the immuno-ORFeome of latent M. tuberculosis. Within the immuno-ORFeome, the rare targets were predominantly latency-associated proteins and secreted proteins, while the preferentially recognized antigens tended to be transmembrane proteins. Six of novel highly-reactive antigens had the potential to distinguish LTBI from active TB and healthy individuals. A multiple-antigen combination set was selected through analysis of various combinations. A panel of 94 archived serum samples was used to validate the diagnostic performance of the multiple-antigen combination set, which had sensitivity of 66.1% (95% CI 52.9, 77.4) and specificity of 87.5% (95% CI 70.1, 95.1). These results provide experimental evidence of the immunogenicity of novel TB proteins that are suitable for the development of serodiagnostic tools for LTBI.

Bacillus Calmette–Guerin (BCG), the only current vaccine against tuberculosis (TB) that is licensed in clinics, successfully protects infants and young children against several TB types, such as TB meningitis and miliary TB, but it is ineffective in protecting adolescents and adults against pulmonary TB. Thus, it is a matter of the utmost urgency to develop an improved and efficient TB vaccine. In this milieu, virus-like particles (VLPs) exhibit excellent characteristics in the field of vaccine development due to their numerous characteristics, including but not limited to their good safety without the risk of infection, their ability to mimic the size and structure of original viruses, and their ability to display foreign antigens on their surface to enhance the immune response. In this study, the HPV16 L1 capsid protein (HPV16L1) acted as a structural vaccine scaffold, and the extracellular domain of Ag85B was selected as the M. tb immunogen and inserted into the FG loop of the HPV16 L1 protein to construct chimeric HPV16L1/Ag85B VLPs. The chimeric HPV16L1/Ag85B VLPs were produced via the Pichia pastoris expression system and purified via discontinuous Optiprep density gradient centrifugation. The humoral and T cell-mediated immune response induced by the chimeric HPV16L1/Ag85B VLP was studied in female C57BL/c mice. We demonstrated that the insertion of the extracellular domain of Ag85B into the FG loop of HPV16L1 did not affect the in vitro stability and self-assembly of the chimeric HPV16L1/Ag85B VLPs. Importantly, it did not interfere with the immunogenicity of Ag85B. We observed that the chimeric HPV16L1/Ag85B VLPs induced higher Ag85B-specific antibody responses and elicited significant Ag85B-specific T cell immune responses in female C57BL/c mice compared with recombinant Ag85B. Our findings provide new insights into the development of novel chimeric HPV16L1/TB VLP-based vaccine platforms for controlling TB infection, which are urgently required in low-income and developing countries.

Long noncoding RNAs (lncRNAs) can directly or indirectly regulate gene expression through interacting with microRNAs (miRNAs). Competitive endogenous RNAs render the roles of lncRNAs more complicated in the process of tumor occurrence and progression. However, the prognostic value of lncRNAs as potential biomarkers and their functional roles as competitive endogenous RNAs have not been clearly described for lung adenocarcinoma (LUAD). In the present study, the aberrant expression profiles of lncRNAs and miRNAs were analyzed at cBioPortal by interrogating LUAD dataset from The Cancer Genome Atlas (TCGA) database with 517 tissue samples. A total of 92 lncRNAs and 125 miRNAs with highly genetic alterations were identified. Further bioinformatics analysis was performed to construct a LUAD-related lncRNA-miRNA-mRNA ceRNA network, which included 24 highly altered lncRNAs, 21 miRNAs and 142 mRNAs. Some key lncRNAs in this network were subsequently identified as LUAD prognosis-related, and of those, CASC15 and LINC01600 both performed the potential prognostic characteristics with LUAD regarding OS and recurrence. Comprehensive analysis indicated that the expression of LINC01600 was significantly associated with KRAS mutation and lymph node metastasis, and CASC15 and LINC01600 were significantly tended towards co-occurrence, which may be due to the similarity of genes co-expressed by these 2 lncRNAs. Our findings provided novel insight into better understanding of ceRNA regulatory mechanisms in the pathogenesis of LUAD and facilitated the identification of potential biomarkers for prognosis.