Coronavirus disease (COVID-19) causes a serious threat to human health. Virus-like particles (VLPs) constitute a promising platform in SARS-CoV-2 vaccine development. In this study, the E, M, and S genes were cloned into multiple cloning sites of a new triple expression plasmid with one p10 promoter, two pPH promoters, and three multiple cloning sites. The plasmid was transformed into DH10 Bac^TMEscherichia coli competent cells to obtain recombinant bacmid. Then the recombinant bacmid was transfected in ExpiSf9^TM insect cells to generate recombinant baculovirus. After ExpiSf9^TM cells infection with the recombinant baculovirus, the E, M, and S proteins were expressed in insect cells. Finally, SARS-CoV-2 VLPs were self-assembled in insect cells after infection. The morphology and the size of SARS-CoV-2 VLPs are similar to the native virions.

Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat for effective treatment of several difficult-to-treat infections in humans. To identify potential new treatment options for MRSA infections, we screened a clinical compound library consisting of 1524 compounds using a growth inhibition assay in 96-well plates. We identified 34 agents which are either bacteriostatic or bactericidal against log-phase clinical MRSA strain USA300. Among them, 9 candidates (thonzonium, cetylpyridinium, trilocarban, benzododecinium, bithionol, brilliant green, chlorquinaldol, methylbenzethonium and green violet) are known antiseptics, 11 candidates are known antibiotics currently recommended for the treatment of MRSA. We identified 9 new drug candidates, 5 of which (thiostrepton, carbomycin, spiramycin, clofazimine and chloroxine) are antibiotics used for treating other infections than S. aureus infections; 4 of which (quinaldine blue, closantel, dithiazanine iodide and pyrvinium pamoate) are drugs used for treating parasitic diseases or cancer. We ranked these new drug candidates according to their MICs against the MRSA strain USA300. Our findings may have implications for more effective treatment of MRSA infections.

Urinary tract infection (UTI), a common clinical infectious disease, is marked by high incidence and frequent recurrence. Recurrent UTIs can cause severe complications, negatively affecting health. The emergence and spread of drug-resistant bacteria present significant challenges to UTI treatment. This article systematically reviews the key immune mechanisms in the body’s defense against UTI pathogens. It discusses various immune response components, such as the urinary tract mucosal epithelium, neutrophils, macrophages, dendritic cells, mast cells, innate lymphocytes, T cells, and B cells, with the aim of providing insights for future UTI research.

Protein subunit vaccines, lacking pathogen-associated molecular patterns that trigger immune responses, rely on adjuvants to induce robust immune responses against the target pathogen. Thus, selection of adjuvants plays a crucial role in the design of protein subunit vaccines. Recently, there has been growing interest in utilizing cGAS-STING agonists as vaccine adjuvants. In this study, we investigated the adjuvant effect of manganese (Mn), a cGAS-STING agonist, on the tuberculosis subunit vaccine Bfrb-GrpE (BG) in a mouse model. Initially, mice were administered with BG-Mn(J), and its immunogenicity and protective efficacy were assessed six weeks after the final immunization. The results showed that Mn(J) enhanced both the cellular and humoral immune responses to the BG vaccine and conferred effective protection against M. tuberculosis H37Ra infection in mice, leading to a significant reduction of 2.0 ± 0.17 Log₁₀ CFU in spleens and 1.3 ± 0.17 Log₁₀ CFU in lungs compared to the PBS control group. Additionally, we assessed the BG-Mn(J) vaccine in a surrogate model of tuberculosis in rabbit skin model. The vaccination with BG-Mn(J) also provided effective protection in the rabbit model, as indicated by a decreased bacterial load at the infection site, minimal pathological damage, and accelerated healing. These findings suggest that Mn(J) holds promise as an adjuvant for tuberculosis vaccines, underscoring its potential to enhance vaccine efficacy and offer protection against tuberculosis infection.

Long-lived memory cell formation and maintenance are usually regulated by cytokines and transcriptional factors. Adjuvant effects of IL-7 have been studied in the vaccines of influenza and other pathogens. However, few studies investigated the adjuvant effects of cytokines and transcriptional factors in prolonging the immune memory induced by a tuberculosis (TB) subunit vaccine. To address this research gap, mice were treated with the Mycobacterium tuberculosis (M. tuberculosis) subunit vaccine Mtb10.4-HspX (MH) plus ESAT6-Ag85B-MPT64_<190–198>-Mtb8.4-Rv2626c (LT70), together with adeno-associated virus-mediated IL-7 or lentivirus-mediated transcriptional factor Id3, Bcl6, Bach2, and Blimp1 at 0, 2, and 4 weeks, respectively. Immune responses induced by the vaccine were examined at 25 weeks after last immunization. The results showed that adeno-associated virus-mediated IL-7 allowed the TB subunit vaccine to induce the formation of long-lived memory T cells. Meanwhile, IL-7 increased the expression of Id3, Bcl6, and bach2—the three key transcription factors for the generation of long-lived memory T cells. The adjuvant effects of transcriptional factors, together with TB fusion protein MH/LT70 vaccination, showed that both Bcl6 and Id3 increased the production of antigen-specific antibodies and long-lived memory T cells, characterized by high proliferative potential of antigen-specific CD4⁺ and CD8⁺ T cells, and IFN-γ secretion in CD4⁺ and CD8⁺ T cells, respectively, after re-exposure to the same antigen. Overall, our study suggests that IL-7 and transcriptional factors Id3 and Bcl6 help the TB subunit vaccine to induce long-term immune memory, which contributes to providing immune protection against M. tuberculosis infection.