Tuberculosis (TB) is a major health problem of global concern. The control of this disease requires appropriate preventive measures, including vaccines. In TB, T helper (Th)1 cytokines provide protection whereas Th2 and T regulatory (Treg) cytokines contribute to the pathogenesis and Th17 cytokines play a role in both protection and pathogenesis. Previous studies with Mycobacterium tuberculosis-specific proteins have identified seven low molecular weight proteins, PE35, ESXA, ESXB, Rv2346c, Rv2347c, Rv3619c, and Rv3620c, as immunodominant antigens inducing Th1-cell responses in humans following natural infection with M. tuberculosis. The aim of this study was to characterize the cytokine responses induced in mice immunized with these proteins, using various adjuvants and delivery systems, i.e. chemical adjuvants (Alum and IFA), non-pathogenic mycobacteria (M. smegmatis and M. vaccae) and a DNA vaccine plasmid (pUMVC6). The immune responses were monitored by quantifying the marker cytokines secreted by Th1 (IFN-γ), Th2 (IL-5), Treg (IL-10), and Th17 (IL-17A) cells. DNA corresponding to pe35, esxa, esxb, rv2346c, rv2347c, rv3619c, and rv3620c genes were cloned into the expression vectors pGES-TH-1, pDE22 and pUMVC6 for expression in Escherichia coli, mycobacteria and eukaryotic cells, respectively. Mice were immunized with the recombinants using different adjuvants and delivery systems, and spleen cells were stimulated in vitro with peptides of immunizing proteins to investigate antigen-specific secretion of Th1 (IFN-γ), Th2 (IL-5), Treg (IL-10), and Th17 (IL-17A) cytokines. The results showed that spleen cells, from mice immunized with all antigens, secreted the protective Th1 cytokine IFN-γ, except ESXB, with one or more adjuvants and delivery systems. However, only Rv3619c consistently induced Th1-biased responses, without the secretion of significant concentrations of Th2, Th17 and Treg cytokines, with all adjuvants and delivery systems. Rv3619c also induced antigen-specific IgG antibodies in immunized mice.
HIV-1 infection and its progression to AIDS remains a significant global health challenge, particularly for low-income countries. Developing a vaccine to prevent HIV-1 infections has proven to be immensely challenging with complex biological acquisition and infection, unforeseen clinical trial disappointments, and funding issues. This paper discusses important landmarks of progress in HIV-1 vaccine development, various vaccine strategies, and clinical trials.
The microorganisms at the workplace contribute towards a large portion of the biodiversity a person encounters in his or her life. Health care professionals are often at risk due to their frontline nature of work. Competition and cooperation between nasal bacterial communities of individuals working in a health care setting have been shown to mediate pathogenic microbes. Therefore, we investigated the nasal bacterial community of 47 healthy individuals working in a clinical research laboratory in Kuwait. The taxonomic profiling and core microbiome analysis identified three pre-dominant genera as Corynebacterium (15.0%), Staphylococcus (10.3%) and, Moraxella (10.0%). All the bacterial genera exhibited seasonal variations in summer, winter, autumn and spring. SparCC correlation network analysis revealed positive and negative correlations among the classified genera. A rich set of 16 genera (q < 0.05) were significantly differentially abundant (LEfSe) across the four seasons. The highest species counts, richness and evenness (P < 0.005) were recorded in autumn. Community structure profiling indicated that the entire bacterial population followed a seasonal distribution (R2-0.371; P < 0.001). Other demographic factors such as age, gender and, ethnicity contributed minimally towards community clustering in a closed indoor laboratory setting. Intra-personal diversity also witnessed rich species variety (maximum 6.8 folds). Seasonal changes in the indoor working place in conjunction with the outdoor atmosphere seems to be important for the variations in the nasal bacterial communities of professionals working in a health care setting.
Brucellosis is a zoonotic disease of major concern in Kuwait and the Middle East. Human brucellosis can be caused by several Brucella species with varying degree of pathogenesis, and relapses are common after apparently successful therapy. The classical biochemical methods for identification of Brucella are time-consuming, cumbersome, and provide information limited to the species level only. In contrast, molecular methods are rapid and provide differentiation at intra-species level. In this study, four molecular methods [16S rRNA gene sequencing, real-time PCR, enterobacterial repetitive intergenic consensus (ERIC)-PCR and multilocus variable-number tandem-repeat analysis (MLVA)-8, MLVA-11 and MLVA-16 were evaluated for the identification and typing of 75 strains of Brucella isolated in Kuwait. 16S rRNA gene sequencing of all isolates showed 90–99% sequence identity with B. melitensis and real-time PCR with genus- and species- specific primers identified all isolates as B. melitensis. The results of ERIC-PCR suggested the existence of 75 ERIC genotypes of B. melitensis with a discriminatory index of 0.997. Cluster classification of these genotypes divided them into two clusters, A and B, diverging at ~25%. The maximum number of genotypes (n = 51) were found in cluster B5. MLVA-8 analysis identified all isolates as B. melitensis, and MLVA-8, MLVA-11 and MLVA-16 typing divided the isolates into 10, 32 and 71 MLVA types, respectively. Furthermore, the combined minimum spanning tree analysis demonstrated that, compared to MLVA types discovered all over the world, the Kuwaiti isolates were a distinct group of MLVA-11 and MLVA-16 types in the East Mediterranean Region.
The 6 kDa early secreted antigen target (ESAT6) is a low molecular weight and highly immunogenic protein of Mycobacterium tuberculosis with relevance in the diagnosis of tuberculosis and subunit vaccine development. The gene encoding the ESAT6 protein is located in the M. tuberculosis-specific genomic region known as the region of difference (RD)1. There are 11 M. tuberculosis-specific RDs absent in all of the vaccine strains of BCG, and three of them (RD1, RD7, and RD9) encode immunodominant proteins. Each of these RDs has genes for a pair of ESAT6-like proteins. The immunological characterizations of all the possible proteins encoded by genes in RD1, RD7 and RD9 have shown that, besides ESAT-6 like proteins, several other proteins are major antigens useful for the development of subunit vaccines to substitute or supplement BCG. Furthermore, some of these proteins may replace the purified protein derivative of M. tuberculosis in the specific diagnosis of tuberculosis by using interferon-gamma release assays and/or tuberculin-type skin tests. At least three subunit vaccine candidates containing ESAT6-like proteins as antigen components of multimeric proteins have shown efficacy in phase 1 and phase II clinical trials in humans.
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