The present paper summarized the global status on Mycobacterium tuberculosis (M. tuberculosis) vaccine development. Novel tuberculosis vaccines in clinical and pre-clinical trials are listed. The new tuberculosis vaccine candidates include recombinant bacillus Calmette-Guérin (BCG), subunit vaccines and therapeutic vaccines. The status of research on new tuberculosis vaccines in China is analyzed. The review also introduced the development tendency of tuberculosis vaccines in the world, such as Human Vaccines Project, whole cell vaccine, multistage subunit vaccines, etc. The issues, opportunities and challenges for tuberculosis vaccine research and development in the future were discussed.

One of the major efforts for the next generation vaccine for tuberculosis prevention is based upon bacillus Calmette-Guérin (BCG). The potential limitations and practical concerns regarding “new generation tuberculosis vaccine based on BCG” are presented in this paper. The practical challenge in designing, the concerns for preclinical pharmacodynamic evaluation and effective clinical evaluation are discussed. We concluded that although a new BCG-based vaccine may reach the goal for better protection than the current BCG, it is difficult to significantly improve the protection for adults. The trials of new vaccines in newborns may not be conducted due to the ethical issues. Control of latent tuberculosis infection is a key step for the prevention of tuberculosis and the new vaccines may not be applied in this population. Therefore, we need new strategies for new generation of mainstream tuberculosis vaccines as there are significant hurdles on the path for BCG-based research and development.

The purpose of the current study is to investigate the molecular mechanisms of tumor necrosis factor α (TNF-α) and interleukin 8 (IL-8) mRNA expressions in THP-1 macrophages challenged by Mycobacterium abscessus subsp. abscessus (Mabs) and Mycobacterium abscessus subsp. massiliense (Mmass). The role of Toll-like receptor 2 (TLR2)-mediated c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling pathways were investigated. First, THP-1 macrophages were cultured in the presence of Mabs and Mmass to stimulate cytokine expression . The mRNA expression levels of TNF-α and IL-8 were analyzed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) after 6 h. The levels of TNF-α and IL-8 mRNA after administration of anti-TLR2 mAb, JNK signaling inhibitor SP600125 and ERK signaling inhibitor U0126 were also detected. The results demonstrated that the levels of TNF-α and IL-8 mRNA in THP-1 cells were significantly upregulated by Mabs and Mmass for 6 h (P<0.05). The stimulated expressions of both TNF-α and IL-8 were significantly downregulated by anti-TLR2 mAb, JNK inhibitor or ERK inhibitor, respectively. It was thus concluded that both Mabs and Mmass could upregulate TNF-α and IL-8 mRNA expressions through TLR2-mediated JNK and ERK pathways.

To analyze the risk factors of infections caused by linezolid-resistant Enterococcus faecalis (E. faecalis), 165 cases from Shenzhen Nanshan District People’s Hospital with E. faecalis infection recorded from January 2010 to September 2015 were studied. The patients were divided into linezolid-sensitive group and linezolid-resistant/intermediate group. E. faecalis mainly came from urine culture (53.94%), and then wound secretion culture (21.82%) and bloodstream culture (6.06%). E. faecalis infection was mainly found in Department of Urology (35.76%) and Department of Hepatobiliary Surgery (9.70%). Both univariate analysis and logistic regression analysis showed that carbapenem exposure and indwelling catheter were associated with linezolid-resistant E. faecalis infections. The results suggest that the clinical application of carbapenems should be strictly controlled, and the management of nosocomial infection should be strengthened.

To investigate the immunological responses of BALB/c mice to herpes simplex virus type 1 (HSV-1) infection, the following factors were followed: strains, infect routes and mouse ages, the dendritic cells (DCs) and HSV-1 specific T cell rate and function in peripheral blood mononuclear cells (PBMCs), serum neutralizing antibody titer, and CD8^＋ T cell infiltration in nervous tissues in HSV-1-infected BALB/c mice. The results showed that 3-week- and 6-week-old BALB/c mice challenged with HSV-1 Mckrae and 17＋ strains through corneal and nasal routes led to an increased rate of DCs in PBMCs, and conferred DC capacity to stimulate HSV-1 specific T cells in vivo. At 35 d post infection, low level interferon γ (IFN-γ)^＋ T cells and no interleukin 4 (IL4)^＋ T cells could be detected in PBMCs, and low level neutralizing antibody was present or absent in serum. Ninety days after BALB/c mice challenged with HSV-1 through subcutaneous and foot pad injection, CD8^＋ T cells could be detected in mouse trigeminal ganglia in different groups. However, HSV-1 specific IFN-γ^＋ T cell and IL4^＋ T cell rates showed divergence between different virus strains and mouse ages. Foot pad injection of BALB/c mice with HSV-1 could elicit higher neutralizing antibody titer compared with subcutaneous injection. This research demonstrated that, infection of different age BALB/c mice with different HSV-1 strains through different routes can stimulate comparable DC maturation and antigen presentation.

Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is essential to establish and sustain viral replication. We recently reported a technique involving HBV recombinant cccDNA (rcccDNA) using Cre/loxP-mediated DNA recombination (rcccDNA^loxP). rcccDNA^loxP could be substantially induced in the nuclei of hepatocytes, which thus represents a useful surrogate for HBV cccDNA-related investigations. In the present study, we described an approach to prepare rcccDNA in an Escherichia coli (E. coli) strain ZYCY10P3S2T based on PhiC31-mediated site-specific recombination (rcccDNA^attR). Purified rcccDNA^attR minicircles were supercoils which demonstrated to support functional HBV expression and replication in the cell culture. Using the technique of hydrodynamic injection, rcccDNA^attR induced significantly prolonged HBV antigenemia in immunocompetent mice, as compared to a regular plasmid encoding linear HBV replicon. Collectively, our study provided a simplified method to surrogate HBV cccDNA in the prokaryotic expression system and in the mouse model. Our results suggested again that rcccDNA is intrinsically stable and could act as a prototype for modeling HBV persistence in mouse livers.

Attenuated Mycobacterium bovis bacillus Calmette-Guérin (BCG) is effective for the prevention of severe tuberculosis infection in childhood, but its protective efficiency shrinks along with children growing up. BCG persisted for a long time after vaccination, therefore it mainly induces short-lived effector memory T cells. This may be the reason why BCG can’t provide long-term protection. Novel tuberculosis subunit vaccine composed of effective antigens with suitable adjuvants could induce Th1 type cell-mediated immune responses and provide protection against tuberculosis. Animal experiments showed that expanding the spectrum of antigens could improve the protective efficacy of subunit vaccine effectively. Moreover, subunit vaccine has been proven to induce long-lived central memory T cells, which helps to provide a longer-term protective immunity compared with BCG. The differentiation of memory T cells is regulated by antigen characteristic and dose, cytokines, transcription factors, and drugs like rapamycin, etc. The study on the subunit vaccine and vaccine-induced immune memory will be helpful to the design and evaluation of novel tuberculosis vaccines.

Tuberculosis (TB) is a serious disease caused by Mycobacterium tuberculosis (M. tuberculosis) infection. Although human beings are considered to be the primary host for this pathogen, the other animals are also implicated in the transmission and (or) infection. Until now, reports showed that animals such as elephants, non-human primates, tapirs, seals, dogs, cats, pigs, rabbits, cattle and birds could be infected by M. tuberculosis. This review mainly described the prevalence and transmission of M. tuberculosis in wild and domestic animals, and summarized the main transmission routes of M. tuberculosis in these animals.

Neutrophils are the first line of defense against invading pathogens. Neutrophils kill pathogens through chemotaxis and phagocytosis. It has been confirmed that neutrophils kill pathogenic microorganisms by engulfing pathogens and secreting antimicrobial protein particles. In 2004, Brinkmann found a new anti-infection mechanism of neutrophils, that is the release of neutrophil extracellular traps (NETs) after activation. NETs are a kind of structure similar to fiber network, which are composed of double-stranded DNA and antibacterial proteins laying on chromatin structure. The role of NETs in the process of anti-infection is capturing and killing pathogenic microorganisms. In recent years, increased evidence has shown that NETs play an important role in inflammatory diseases, and the pathological process in acute and chronic inflammatory diseases would be affected by NET generation and degradation. This article mainly summarizes the latest research progress on NETs in the characteristics, generation mechanism, antibacterial activity, and the effect in inflammatory diseases; provides new ideas and directions for the treatment and drug development for inflammatory diseases.

Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (CRISPR/Cas) is an acquired immune system developed in evolution of prokaryotes. It provides an immune protection to resist invasion of foreign DNAs or RNAs, such as phages, plasmids and the other mobile genetic elements. CRISPR loci have been identified in genomes of Staphylococcus species. The spacers of the CRISPR arrays usually match with the genes on phages or plasmids derived from the other species or strains of Staphylococcus, and may provide a function to interfere the transmission of exogenous elements related with bacterial virulence, drug resistance and biofilm formation. This review focuses on the unique structure and function of staphylococcal CRISPR/Cas systems.