The sex‐determining region on the Y chromosome (SRY) has 2 nuclear localization signals (NLSs) that flank the DNA binding high mobility group (HMG) domain;the β‐NLS and the CaM‐NLS, which mediate nuclear transport through importin β1 (Impβ1) and the calcium‐binding protein calmodulin (CaM), respectively. Here we reconstitute the nuclear import mediated by the 2 NLSs for the first time in vitro , establishing Ran independence of CaM‐NLS‐dependent transport. The β‐ and CaM‐NLSs were found to be independently functional out of the context of the SRY HMG domain, dependent on Impβ1 and CaM binding, respectively. Intriguingly, direct protein binding assays also indicated competitive binding of Impβ1 and CaM to the SRY HMG domain. To assess the potential role of intracellular calcium in modulating SRY nuclear accumulation, Cos‐7 cells expressing SRY and control constructs were treated with agents elevating or reducing intracellular Ca ²⁺ levels. The in vivo results, supported by experiments in vitro where transport was assessed with or without 2 µMCa ²⁺ , indicate a Ca ²⁺ ‐dependent mode of nuclear transport via the CaM‐NLS/CaM, with inhibition of β‐NLS/Impβ1‐mediated nuclear import by intracellular Ca ²⁺ . The results imply mutual exclusivity of nuclear transport via the 2 NLSs with intracellular Ca ²⁺ as the switch between the 2.—Kaur, G. Jans, D. A. Dual nuclear import mechanisms of sex determining factor SRY: intracellular Ca ²⁺ as a switch. FASEB J. 25, 665–675 (2011). www.fasebj.org

Candida albicans, along with several non-albicans Candida species, comprise a prominent fungal pathogen in humans, leading to candidiasis in various organs. The global impact of candidiasis in terms of disease burden, suffering, and fatalities is alarmingly high, making it a pressing global healthcare concern. Current treatment options rely on antifungal drugs such as azoles, polyenes, and echinocandins but are delimited due to the emergence of drug-resistant strains and associated adverse effects. The current review highlights the striking absence of a licensed antifungal vaccine for human use and the urgent need to shift our focus toward developing an anti-Candida vaccine. A number of factors affect the development of vaccines against fungal infections, including the host, intraspecies and interspecies antigenic variations, and hence, a lack of commercial interest. In addition, individuals with a high risk of fungal infection tend to be immunocompromised, so they are less likely to respond to inactivated or subunit whole organisms. Therefore, it is pertinent to discover newer and novel alternative strategies to develop safe and effective vaccines against fungal infections. This review article provides an overview of current vaccination strategies (live attenuated, whole-cell killed, subunit, conjugate, and oral vaccine), including their preclinical and clinical data on efficacy and safety. We also discuss the mechanisms of immune protection against candidiasis, including the role of innate and adaptive immunity and potential biomarkers of protection. Challenges, solutions, and future directions in vaccine development, namely, exploring novel adjuvants, harnessing the trained immunity, and utilizing immunoinformatics approaches for vaccine design and development, are also discussed. This review concludes with a summary of key findings, their implications for clinical practice and public health, and a call to action for continued investment in candidiasis vaccine research.

The Bacille Calmette-Guérin or BCG vaccine, the only vaccine available against Mycobacterium tuberculosis can induce a marked Th1 polarization of T-cells, characterized by the antigen-specific secretion of IFN-γ and enhanced antiviral response. A number of studies have supported the concept of protection by non-specific boosting of immunity by BCG and other microbes. BCG is a well-known example of a trained immunity inducer since it imparts ‘non-specific heterologous’ immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the recent pandemic. SARS-CoV-2 continues to inflict an unabated surge in morbidity and mortality around the world. There is an urgent need to devise and develop alternate strategies to bolster host immunity against the coronavirus disease of 2019 (COVID-19) and its continuously emerging variants. Several vaccines have been developed recently against COVID-19, but the data on their protective efficacy remains doubtful. Therefore, urgent strategies are required to enhance system immunity to adequately defend against newly emerging infections. The concept of trained immunity may play a cardinal role in protection against COVID-19. The ability of trained immunity-based vaccines is to promote heterologous immune responses beyond their specific antigens, which may notably help in defending against an emergency situation such as COVID-19 when the protective ability of vaccines is suspicious. A growing body of evidence points towards the beneficial non-specific boosting of immune responses by BCG or other microbes, which may protect against COVID-19. Clinical trials are underway to consider the efficacy of BCG vaccination against SARS-CoV-2 on healthcare workers and the elderly population. In this review, we will discuss the role of BCG in eliciting trained immunity and the possible limitations and challenges in controlling COVID-19 and future pandemics.

Mycobacterium tuberculosis (Mtb) is an etiological agent of tuberculosis (TB). Tuberculosis is a mounting problem worldwide. The only available vaccine BCG protects the childhood but not adulthood form of TB. Therefore, efforts are made continuously to improve the efficacy of BCG by supplementing it with other therapies. Consequently, we explored the possibility of employing Mycobacterium immunogenum (Mi) to improve BCG potential to protect against Mtb. We report here the genome mining, comparative genomics, immunological and protection studies employing strain CD11_6 of Mi. Mycobacterium immunogenum was isolated from duodenal mucosa of a celiac disease patient. The strain was whole genome sequenced and annotated for identification of virulent genes and other traits that may make it suitable as a potential vaccine candidate. Virulence profile of Mi was mapped and compared with two other reference genomes i.e. virulent Mtb strain H37Rv and vaccine strain Mycobacterium bovis (Mb) AFF2122/97. This comparative analysis revealed that Mi is less virulent, as compared to Mb and Mtb, and contains comparable number of genes encoding for the antigenic proteins that predict it as a probable vaccine candidate. Interestingly, the animals vaccinated with Mi showed significant augmentation in the generation of memory T cells and reduction in the Mtb burden. The study signifies that Mi has a potential to protect against Mtb and therefore can be a future vaccine candidate against TB.

History is replete with incidents of pandemics like Influenza flu, Ebola, and now, the recent most novel Corona virus. The spread of these infectious beings is mostly fatal, highly explosive, and unmanageable, bringing with them severe social, economic, physiological and psychological impacts. Revisiting such historical events through literature is quite insightful. One feels empathetic and connected with the characters. This paper intends to revisit the settings and situations of Oran, the centre of pandemic in Albert Camus’ The Plague and compare it with the current, globally occurring, pandemic of Corona virus. The purpose is to understand how literature connects with real life and becomes a source of hope, strength and motivation for the readers.