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The effect of the 1918 influenza pandemic on other diseases is a neglected topic in historical epidemiology. This paper takes up the hypothesis that the influenza pandemic affected the long-term decline of tuberculosis through selective mortality, such that many people with tuberculosis were killed in 1918, depressing subsequent tuberculosis mortality and transmission. Regularly collected vital statistics...
The ongoing evolution of BCG after its introduction in 1921 resulted in strains that differ genetically and phenotypically. Based on a genomic deletion (Region of Difference 2 or RD2) that occurred between 1927 and 1931, BCG strains can be sub-classified by the presence or absence of RD2. The existence of other mutations that distinguish BCG strains precludes simple comparison of RD2-positive and...
New TB vaccines are urgently needed because of the apparent lack of effect of the BCG vaccine on rates of adult contagious pulmonary tuberculosis and the risk of disseminated BCG disease in immunocompromised individuals. Since BCG appears to protect children, the primary target for vaccine development is a booster vaccine for adults but such vaccines ideally need to be able to efficiently prime mycobacterially...
Protein subunit vaccines are an attractive mode of immunisation against infectious diseases but the approach is hampered by the lack of suitable adjuvants for human use. We investigated if antigen targeting to the endocytic cell receptor Dec-205 on dendritic cells (DCs) could induce a protective immune response to Mycobacterium tuberculosis (MTB) infection in the absence of conventional adjuvants...
Tuberculosis (TB) caused by Mycobacterium tuberculosis continues to be a leading cause of mortality among bacterial diseases, and the bacillus Calmette-Guérin (BCG) is the only licensed vaccine for human use against this disease. TB prevention and control would benefit from an improved method of BCG vaccination that simplifies logistics and eliminates dangers posed by hypodermic needles without compromising...
The development of improved vaccines against Mycobacterium tuberculosis has been hindered by a limited understanding of the immune correlates of anti-tuberculosis protective immunity. In this study, we examined the relationship between long-term anti-tuberculosis protection and the mycobacterial-specific CD4 multifunctional T (MFT) cell responses induced by five different TB vaccines (live-attenuated,...
Mycobacterium bovis infection is widespread in Eurasian badger (Meles meles) populations in Great Britain and the Republic of Ireland where they act as a wildlife reservoir of infection for cattle. Removal of infected badgers can significantly reduce the incidence of bovine tuberculosis (TB) in local cattle herds. However, control measures based on culling of native wildlife are contentious and may...
The endpoint definition for infant tuberculosis (TB) vaccine trials should match the TB disease phenotype expected in the control arm of the study population. Our aim was to analyse selected combinations of the clinical, radiological, and microbiological features of pulmonary TB among children investigated under vaccine trial conditions, in order to estimate case frequency for a range of expected...
The limited efficacy of the BCG vaccine for tuberculosis, coupled with emerging information suggesting that it is poorly protective against newly emerging strains of Mycobacterium tuberculosis such as the W-Beijing isolates, makes it paramount to search for more potent alternatives. One such class of candidates is attenuated mutants derived from M. tuberculosis itself. We demonstrate here, in an initial...
To improve the conventional BCG vaccine in cake appearance and integrity, a new formulation with corresponding freeze drying cycle was developed for a recombinant BCG vaccine. The new formulation contains mannitol as a bulking agent, and trehalose, sucrose and sodium glutamate as stabilizers. The formulation and freeze drying cycle were tested with different super cooling rates and secondary drying...
We have previously described the development of a live, fully attenuated Mycobacterium tuberculosis (Mtb) vaccine candidate strain with two independent attenuating auxotrophic mutations in leucine and pantothenate biosynthesis. In the present work, those studies have been extended to include testing for protective efficacy in a long-term guinea pig survival model and safety testing in the highly tuberculosis...
Rv3097c of Mycobacterium tuberculosis encoding lipase (LipY) was overexpressed in Mycobacterium bovis BCG. Efficacy of recombinant BCG to protect against infection of M. tuberculosis was evaluated in mice. Whereas the parent BCG vaccine protected the mice against infection, recombinant BCG overexpressing LipY offered no protection as judged by viable counts of tubercule bacilli in lungs, weight of...
BCG revaccination is still used in some tuberculosis endemic countries. Until now, the little evidence available suggested that BCG revaccination confers very limited additional protection, although there was no information on whether protection depends on the setting and age of revaccination, or if protection increases with time since vaccination. Here we report on an extended follow up of the BCG-REVAC...
The development of effective anti-Tuberculosis (TB) vaccines is an important step towards improved control of TB in high burden countries. Subunit vaccines are advantageous in terms of safety, particularly in the context of high rates of HIV co-infection, but they must contain sufficient Mycobacterium tuberculosis antigens to stimulate immunity in genetically diverse human populations. We have used...
Tuberculosis is a major health concern. Non-living tuberculosis (TB) vaccine candidates may not only be safer than the current vaccine (BCG) but could also be used to boost BCG to enhance or elongate protection. No subunit vaccines, however, are currently available for TB. To address this gap and to improve the global TB situation, we have generated a defined subunit vaccine by genetically fusing...
An efficient global control of tuberculosis requires development of alternative vaccination strategies that can enhance the efficacy of existing BCG vaccine. In this study, we evaluated the protective efficacy of a recombinant BCG (rBCG) vaccine over-expressing iron-cofactored superoxide dismutase (SOD-A), one of the prominent oxidative stress response proteins of Mycobacterium tuberculosis. Contrary...
Tuberculosis remains a major cause of morbidity and mortality worldwide. Bacille Calmette Guerin (BCG) is the current vaccine for tuberculosis. The absence or presence of a scar is used as an indicator of previous vaccination.To determine the sensitivity of the BCG scar as an indicator of previous vaccination.We conducted a descriptive hospital based study of 100 infants attending two centres for...
Bacille Calmette–Guérin (BCG) is the vaccine against tuberculosis (TB), but has varied efficacy in different geographical locations. Recombinant strategies to genetically modify the organism to enhance the quality of the immune response have aimed at improving BCG efficacy. Here we describe such a strategy using rBCGΔureC∷hly expressing defined latency-associated antigens and test this construct for...
The hallmark of a vaccine is to induce long-term protective immunity against the pathogen. The use of Mycobacterium bovis BCG as a vaccine against tuberculosis has been problematic in that immunity induced by BCG wanes over time and it may be less effective against more virulent strains of Mycobacterium tuberculosis. Thus it is important to determine what factors might be associated with waning or...
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