The emergence of nosocomial multidrug-resistant Klebsiella pneumoniae is an escalating public health threat worldwide. The prevalence of nosocomial infections due to K. pneumoniae was recorded up to 10%. In this systematic review and meta-analysis, which were conducted according to the guidelines of Preferred Reporting Items for Systematic Review and Meta-Analysis, 1092 articles were screened from four databases of which 47 studies fulfilled the selected criteria. By performing a random-effect model, the pooled prevalence of nosocomial multidrug-resistant K. pneumoniae was estimated at 32.8% (95% CI, 23.6–43.6), with high heterogeneity (I2 98.29%, p-value < 0.001). The estimated prevalence of this pathogen and a few related studies were discussed, raising awareness of the spread of multidrug-resistant K. pneumoniae in the healthcare setting. The emergence of nosocomial multidrug-resistant K. pneumoniae is expected to increase globally in the future, and the best treatments for treating and preventing this pathogen should be acknowledged by healthcare staff.

The evidence of hypercholesterolaemia (HC) being a significant contributor to the progression of ischemic heart diseases (IHDs), particularly myocardial infarction (MI) is steadily increasing globally [1]. However, data on the establishment of MI-associated diet-induced HC rat model are lacking.   Hence, this study aimed to establish an MI-associated diet-induced HC rat model, allowing a better understanding of the pathological changes of this rat model. A total of 6 male Sprague Dawley rats weighing 200-250 were randomly allotted into 2 groups; Control and HC-MI. Control rats were fed with standard pellet, while HC rats were fed with a self-made high-cholesterol diet (HCD) for 10 weeks. The recipe for the HCD was adopted from a previous study [2] with slight modification. At the end of 10th week, MI was induced with the administration of isoprenaline (85 mg/kg, s.c) for 2 consecutive days [3].   In this study, 10 weeks of HCD significantly increased body mass index (BMI), triglyceride, and total cholesterol but not fasting blood glucose level in the HC group compared to the control group, suggestive of obese and HC state (Figure 1). MI was also evident by prominent observation of myocardial necrosis accompanied by infiltration of inflammatory cells in cardiac histology, although cardiac troponin T was not significantly elevated (Figure 2). Although liver function test showed significant elevation of AST but not ALT, but liver histological observation showed the presence of mixed steatosis and ballooning degeneration, suggestive of non-alcoholic fatty liver disease development (Figure 3). Nonetheless, kidney function test revealed a significant creatinine elevation but not urea level (Figure 4).   Collectively, these findings suggest that supplementation of HCD for 10 weeks together with administration of isoprenaline successfully developed a rat model of HC with MI as shown across elevated systemic cholesterol level, BMI, and myocardial necrosis. This study provides useful data on the establishment of the model which could be used in the future.

Adeno-associated virus (AAV) is a very tiny (20-26 nm) icosahedral and non-enveloped virus, and it belongs to the Parvoviridae family. AAV vectors are the most widely used option for gene therapy and delivery of therapeutic antibodies due to their relatively low immunogenicity, high safety profile, broad tropism, and their tendency to maintain long-term gene expression [1]. AVV vectors are developed by transfection of human embryonic kidney (HEK) 293 T cells with transgene, packaging and helper plasmids [2]. Several clinical studies have investigated the use of AAV vectors for gene therapy in treating of Parkinson’s disease, Alzheimer’s disease, heart disease, and prostate cancer [3]. AAV vectors have previously been used to treat muscular diseases, but in recent years, their usage as vaccine vectors to cure or prevent infectious diseases including HIV, HPV, and influenza has expanded [4].   Here, we discuss the advantages and disadvantages of the use of AAV in vaccine development, and future approaches in improving the drawbacks caused by AAV-based vaccines. Numerous animal investigations have been conducted to explore vaccine vectors against various illnesses, suggesting a possibility for AAV-based vaccinations. Clinical studies on humans are, however, uncommon because, in contrast to other viral vectors, AAV induces a poor humoral and cellular immune response. Additionally, infectious vaccinations often target a large group of healthy individuals across a variety of ages, including children and teenagers. Therefore, compared to AAV-based gene therapies, vaccinations based on AAV vectors need to be more cost-effective and need more robust safety control.   According to several research, AAV vector vaccines have been shown to induce a stronger or longer lasting antibody response in comparison to other vaccination approaches, such as DNA, recombinant proteins, inactivated viruses, or virus-like particles (VLPs) [5]. However, AAV vectors are thought to have a low immunogenic profile in comparison to other viral vectors. The main limitations of AAV vectors are their low transgenic capacity and widespread pre-existing immunity in humans [6]. Currently, strategies for improving AAV immunogenicity and circumventing pre-existing immunity are actively being investigated. The research undertaken so far have highlighted numerous significant benefits of AAV vectors for immunisation. Despite all the advantages, there are still a variety of challenges that limit the use of these vectors as a vaccine in humans. Thus, it is necessary to overcome these challenges in order to make AAV-based vaccines effective.

It is now known that the existing vaccination, Bacille Calmette-Guérin (BCG), is unable to stop the global Tuberculosis (TB) epidemic, and TB continues to pose a serious threat to public health [1]. Mycobacterium tuberculosis (Mtb), the causing agent, enters the body by inhalation, causing TB predominantly a respiratory infection [1]. Therefore, there is solid evidence to support the idea that a mucosally administered TB vaccination would be more successful than one administered systemically. Our team in Universiti Sains Malaysia (USM) has been working with several organisations in conjunction with Malaysia’s National Vaccine Roadmap (PPVN) to address this problem as well as the government's goal to produce vaccines that are high-quality, efficient, and secure following the guidelines established by the National Pharmaceutical Regulatory Agency (NPRA). Therefore, the development of TB mucosal vaccines over the past few years for worldwide as well as in USM is outlined in this presentation. It aims to discuss immunological and practical factors in the development of mucosal vaccines and emphasises some of the current and future approaches in USM. As a result, it is acknowledged globally that matching the path of infection with the path of immunisation is an appealing strategy for the development of TB vaccines. Several approaches have been made in USM to produce a vaccine candidate that significantly induces mucosal immunity. The design of the study showed the manipulation of IgA, which is a hallmark of mucosal immunity, with multi-epitopes of TB to produce IgA: TB recombinant protein by using goat’s milk as a bioreactor. The concept of oral immunisation in-vivo also is an important approach in our effort to maximise the production of the immune system at the point of entry of bacteria. In a conclusion, as a boost to a prior respiratory or systemic immunisation, the mucosal method might be more effective. In addition to systemic immunity obtained by injected vaccines, vaccines to induce pathogen-specific IgA are being developed to provide a first line of defence at these entry sites. Therefore, combining these concepts into developing new recombinant vaccine against TB would be a promising alternative.