Recombinant adenovirus (rAd) vectors are being investigated as vaccine delivery vehicles in preclinical and clinical studies. rAds constructed from different serotypes differ in receptor usage, tropism, and ability to activate cells, aspects of which likely contribute to their different immunogenicity profiles. In this study, we compared the infectivity and cell ...

After a 12-year hiatus, military recruit training centers resumed administration of adenovirus type 4 and type 7 vaccine, live, oral (adenovirus vaccine) to trainees beginning in October of 2011. Subsequently, rates of febrile respiratory illnesses (FRI) and adenovirus isolations markedly declined. These findings are consistent with those of a placebo-controlled ...

Inhaled therapies in the form of drugs or vaccines for tuberculosis treatment were reported about a decade ago. Experts around the world met to discuss the scientific progress in inhaled therapies at the international symposium "Optimization of inhaled Tuberculosis therapies and implications for host-pathogen interactions" held in New Delhi, India ...

Although the concept of Reverse Vaccinology was first pioneered for sepsis and meningococcal meningitidis causing bacterium, Neisseria meningitides, no broadly effective vaccine against serogroup B meningococcal disease is yet available. In the present investigation, HLA distribution analysis was undertaken to select three most promiscuous T-cell epitopes out of ten computationally ...

Neisseria gonorrhoeae causes the common sexually transmitted infection, gonorrhea. This microorganism is an obligate human pathogen, existing nowhere in nature except in association with humans. For growth and proliferation, N. gonorrhoeae requires iron and must acquire this nutrient from within its host. The gonococcus is well-adapted for growth in diverse ...

Interleukin-12 (IL-12) and IL-23 (which share a p40 subunit) are pivotal cytokines in the generation of protective Th1/Th17-type immune responses upon infection with the intracellular pathogen Mycobacterium tuberculosis. The role of IL-12 and IL-23 in protection conferred by the tuberculosis vaccine Mycobacterium bovis bacillus Calmette-Guérin (BCG) is, however, less well ...

Pulmonary delivery of vaccines against airborne infection is being investigated worldwide, but there is limited effort directed at developing inhaled vaccines for tuberculosis (TB). This review addresses some of the challenges confronting vaccine development for TB and attempts to link these challenges to the promises of mucosal immunity offered by ...

With almost a dozen vaccine candidates in clinical trials, tuberculosis (TB) research and development is finally reaping the first fruits of its labors. Vaccine candidates in clinical trials may prevent TB disease reactivation by efficiently containing the pathogen Mycobacterium tuberculosis (Mtb). Future research should target vaccines that achieve sterile eradication ...

In July 2008 a case of smear-positive pulmonary tuberculosis (TB) in a white UK-born nursery teacher was notified in London. The case had been symptomatic for 9 months while working in the nursery. The outbreak is described and the protective effect of BCG vaccination against latent Mycobacterium tuberculosis infection as ...

One third of the world's population is infected with Mycobacterium tuberculosis (M.tb). A vaccine that would prevent progression to TB disease will have a dramatic impact on the global TB burden. We propose that antigens of M.tb that are preferentially expressed during latent infection will be excellent candidates for post-exposure ...

Mycobacterium bovis BCG-vaccination in the guinea pig model of tuberculosis (TB) is sufficiently protective that candidate TB vaccines are judged against this. Little is understood about how the BCG vaccine works and, in the absence of a definitive correlate of protection, it is difficult to interpret the significance of novel ...

T-cell-based gamma interferon (IFN-γ) release assays (IGRAs) using Mycobacterium tuberculosis-specific antigens have shown higher sensitivity and specificity than the routine tuberculin skin test (TST). However, the effects of Mycobacterium bovis BCG vaccination and anti-tuberculosis (TB) treatment on dynamic T-cell responses to M. tuberculosis-specific antigens in active TB cases have rarely ...

Despite the widespread use of the childhood vaccine against tuberculosis (TB), Mycobacterium bovis bacillus Calmette-Guérin (BCG), the disease remains a serious global health problem. A successful vaccine against TB that replaces or boosts BCG would include antigens that induce or recall the appropriate T cell responses. Four Mycobacterium tuberculosis (Mtb) ...

To improve the current vaccine against tuberculosis, a recombinant strain of Mycobacterium bovis bacillus Calmette-Guérin (rBCG) expressing a Mycobacterium tuberculosis vaccine candidate antigen (MPT64) in strong association with the mycobacterial cell wall was developed. To deliver the candidate antigen on the surface, we fused the mpt64 gene to the sequence ...

Prompt diagnosis of Mycobacterium tuberculosis (MTB) infection is an essential step in tuberculosis control and elimination. However, it is often difficult to accurately diagnose pediatric tuberculosis (TB). The tuberculin test (TST) may have a low specificity because of cross-reactivity with antigens present in Mycobacterium bovis bacillus Calmette-Guerin (BCG) and other ...

Early secretory antigen target 6 (ESAT-6) is a dominant target for cell-mediated immunity in the early phase of tuberculosis (TB) in patients with TB, causing T-cell proliferation and gamma interferon (IFN-γ) production, which has been considered to be a protective antigen that can be used for future vaccine development. Ag85A ...

Failure to convert (persistent sputum and/or culture positivity) while on antituberculosis (anti-TB) treatment at the end of the second month of anti-TB therapy has been reported to be a predictor of treatment failure. Factors that could be associated with persistent bacillary positivity at the end of the second month after ...

The currently used vaccine against tuberculosis, Bacille Calmette-Guérin (BCG), has variable efficacy, so new vaccine development is crucial. In this study, we evaluated a recombinant vaccine prepared from non-pathogenic Mycobacterium smegmatis (rMS) that expresses a fusion of early secreted antigenic target 6-kDa antigen (ESAT6) and culture filtrate protein 10 (CFP10). ...

This review hopes to improve the selection of new tuberculosis (TB) vaccines by providing several perspectives on the immunization of humans, mice, guinea pigs, rabbits, and monkeys which have not usually been considered. (i) In human TB vaccine trials, the low rate of healing of Mycobacterium bovis BCG lesions (used ...

Vaccination has been identified as a promising control strategy for tuberculosis in both humans and cattle. Recent heterologous prime-boost approaches combining BCG vaccination with subunit boosts have shown considerable promise in both fields. However, the identification of further protective antigens is still a research priority. In this paper we have ...

Tuberculosis (TB) remains to be a major infectious disease throughout the world. However, the current vaccine for TB has variable protective efficacy, and there is no commercially available serodiagnostic test for this disease with acceptable sensitivity and specificity for routine laboratory use. One of the potential strategies in developing a ...

With the evidence showing the protection variability of bacille Calmette-Guérin, new potential vaccines for tuberculosis have been tested around the world. One of the general concerns in tuberculosis vaccine development is the possibility of priming the host immune system with prior exposure to environmental mycobacteria antigens, which can change the ...

The purpose was to determine IFN-g release as a response to vaccination against tuberculosis in dairy heifers under commercial settings. Four-hundred pregnant heifers from ten herds were randomly allocated into four groups: (1) unvaccinated, (2) BCG vaccinated, (3) BCG vaccinated plus a CFPP400μg+polygen boost, and (4) BCG vaccinated plus a ...

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only tuberculosis (TB) vaccine currently available, but its efficacy against adult pulmonary TB remains controversial. BCG induces specific immune responses to mycobacterial antigens and may elicit protective immunity against TB. TB remains a major public health problem, especially among the elderly, yet the ...

Infection usually leads to the development of acquired immune responses associated with clearance or control of the infecting organism. However, if not adequately regulated, immune-mediated pathology can result. Tuberculosis is a worldwide threat, and development of an effective vaccine requires that the protective immune response to Mycobacterium tuberculosis (Mtb) be ...

Bacille Calmette Guérin substrain Moreau Rio de Janeiro is an attenuated strain of Mycobacterium bovis that has been used extensively as an oral tuberculosis vaccine. We assessed its potential as a challenge model to study clinical and immunological events following repeated mycobacterial gut infection. Seven individuals received three oral challenges ...

Protection against pulmonary tuberculosis (TB) by vaccination is often ascribed to the presence of TB-reactive T cells in the lung before infection. Challenging this view, new studies analyzing vaccine-induced T cells in various tissue compartments after parenteral immunization suggest a poor correlation between the presence of anti-TB T cells in ...

Immunization with Mycobacterium bovis Bacille Calmette-Guerin (BCG) did not induce adequate Th1 responses to the latency antigen, HspX of M. tuberculosis. To increase the immunogenicity and protective efficacy of BCG, a recombinant BCG strain over-expressing antigen HspX (rBCG::X) was constructed. The recombinant strain rBCG::X expressed high levels of both HspX ...

The establishment of an aerosol challenge model in nonhuman primates (NHPs) for the testing of vaccines against Mycobacterium tuberculosis would assist the global effort to optimize novel vaccination strategies. The endpoints used in preclinical challenge studies to identify measures of disease burden need to be accurate and sensitive enough to ...

Leukotrienes are reported to be potent proinflammatory mediators that play a role in the development of several inflammatory diseases such as asthma, rheumatoid arthritis and periodontal disease. Leukotrienes have also been associated with protection against infectious diseases. However, the role of leukotrienes in Mycobacterium tuberculosis infection is not understood. To ...

The elderly are particularly susceptible to infectious diseases such as influenza, bacterial pneumonia, and tuberculosis. Current vaccines are only partially protective in old age, which makes the elderly a critical target group for the development of new vaccine strategies. The recognition of pathogens via toll like receptors (TLR) and the ...

All newborns in Hong Kong are given bacille Calmette-Guérin vaccinations. Reported complications include formation of regional and extra-regional localised abscesses, osteomyelitis, and lymphadenitis. Several cases of bacille Calmette-Guérin osteomyelitis have been reported in Europe, but there are few reports of this in Asia. To the author's knowledge, this is the ...

Tuberculosis (TB) remains a threat to global health. While advances in diagnostics and treatment are crucial to the containment of the epidemic, it is likely that elimination of the disease can only be achieved through vaccination. Vaccine-induced protection from Mycobacterium tuberculosis is dependent, at least in part, on a robust ...

New vaccines are urgently needed if we want to reach the goal of substantially reducing the incidence of tuberculosis by 2050. Despite a steady increase in funding over the past decade, there is still a striking financial shortfall for vaccine research and development for tuberculosis. Yet, around ten vaccine candidates ...

Current tuberculosis (TB)-control methods, which do not include an adequate vaccine, do not effectively block transmission of TB. Modeling studies show that mass vaccination campaigns using new vaccines could prevent 85.9 million new cases and 14.5 million deaths from 2015 through 2050 in southern Asia alone. After a dearth of ...

Eleven new tuberculosis (TB) vaccines are in various phases of clinical trials. These include subunit vaccines to improve the current vaccine BCG, and recombinant BCG to substitute for BCG, both given pre-exposure to prevent active disease. A plethora of potential candidates have reached various stages of the pre-clinical development pipeline, ...

Tuberculosis is still one of the main challenges to human global health, leading to about two million deaths every year. One of the reasons for its success is the lack of efficacy of the widely used vaccine Mycobacterium bovis BCG. In this article, we analyze the potential use of an ...

To evaluate the usefulness of the American cotton rat (Sigmodon hispidus) in the evaluation of vaccine-induced resistance, we infected BCG-vaccinated and non-vaccinated cotton rats with Mycobacterium tuberculosis (H37Rv) via the respiratory route. Lung histopathology of these animals showed loose, disorganized granulomas which were non-necrotic up to 8 weeks post-infection. Moreover, ...

OBJECTIVE: To compare the most recent commercial interferon-gamma release assay (IGRA), the QuantiFERON-TB Gold In-Tube (QFT-GIT), with the tuberculin skin test (TST) in Greek army recruits who were bacille Calmette-Guérin (BCG) vaccinated during childhood and had no history of tuberculosis (TB) exposure. METHOD: We conducted a cross-sectional comparison study of ...

Most novel vaccines against infectious diseases are based on recombinant Ag; however, only few studies have compared Ag-specific immune responses induced by natural infection with that induced by the same Ag in a recombinant form. Here, we studied the epitope recognition pattern of the tuberculosis vaccine Ag, TB10.4, in a ...

Vaccination has been discussed as a practical option to control bovine tuberculosis in countries where a wildlife reservoir of the disease is present. African buffaloes (Syncerus caffer) are the main wildlife reservoir of Mycobacterium bovis in certain South African game parks and vaccination is not only the most promising but ...

The current tuberculosis (TB) vaccine bacillus Calmette-Gu?rin (BCG) fails to protect against adult pulmonary TB. Yet, its capacity to control miliary TB in newborn infants forms the basis for development of novel vaccine candidates. These either exploit genetic modification of BCG to create a viable replacement vaccine or use BCG ...

Tuberculosis (TB) is an international public health priority and kills almost two million people annually. TB is out of control in Africa due to increasing poverty and HIV coinfection, and drug-resistant TB threatens to destabilize TB control efforts in several regions of the world. Existing diagnostic tools and therapeutic interventions ...

According to WHO, about one third of the world's population is infected with bacteria of the Mycobacterium tuberculosis complex. Currently there is globally 9.15 million recorded cases of overt tuberculosis (TB) annually and due to lack of adequate diagnostics presumably a large but unknown number of non-recorded cases. TB is ...

A third of the world's population is infected with Mycobacterium tuberculosis, and 2 million people die from tuberculosis every year. The only tuberculosis vaccine currently available is an attenuated strain of Mycobacterium bovis BCG, although its efficacy against adult tuberculosis disease remains controversial. Furthermore multi-drug resistant tuberculosis is becoming big ...

Novel immunization strategies are needed to enhance the global control of tuberculosis (TB). In this study, we assessed the immunizing activity of a recombinant modified vaccinia Ankara (MVA) construct (MVA/IL-15/5Mtb) which overexpresses five Mycobacterium tuberculosis antigens (antigen 85A, antigen 85B, ESAT6, HSP60, and Mtb39), as well as the molecular adjuvant ...

Though widely used, the BCG vaccine has had little apparent effect on rates of adult pulmonary tuberculosis. Moreover, the risk of disseminated BCG disease in immunocompromised individuals means that improved TB vaccines ideally need to be able to efficiently prime mycobacterially-na?ve individuals as well as boost individuals previously vaccinated with ...

AERAS-402 is a novel tuberculosis vaccine designed to boost immunity primed by bacillus Calmette-Guérin (BCG), the only licensed vaccine. We investigated the safety and immunogenicity of AERAS-402 in healthy Mycobacterium tuberculosis-uninfected BCG-vaccinated adults from a tuberculosis-endemic region of South Africa. Escalating doses of AERAS-402 vaccine were administered intramuscularly to each ...

Tuberculosis remains a major human health problem worldwide, and strategies for its prevention include the generation and characterization of new recombinant vaccines containing immunodominant antigens from Mycobacterium tuberculosis. By comparing the secretomes of wild-type Mycobacterium bovis and a PstS1-recombinant M. bovis BCG vaccine substrain (rBCG38), we identified six conserved hypothetical ...

Developing effective prophylactics to combat tuberculosis is currently in an exploratory stage. The HIV pandemic and emergence of multi- and extensively drug-resistant strains of Mycobacterium tuberculosis indicate that the current preventive measures against this ever-evolving pathogen are inadequate. The currently available vaccine BCG in its present form affords variable protection ...