Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a single-centre, randomised, double-blind, placebo-controlled, phase 2 trial.

Background: A recombinant adenovirus type-5 vector-based vaccine expressing the glycoprotein of Ebola Zaire Makona variant showed good safety and immunogenicity in a phase 1 trial of healthy Chinese adults. We aimed to assess the safety and immunogenicity of this vaccine in healthy adults in Sierra Leone and to determine the optimal dose.

Methods: We did a single-centre, randomised, double-blind, placebo-controlled, phase 2 clinical trial at Sierra Leone-China Friendship Hospital, Freetown, Sierra Leone.

Implementing an Ebola Vaccine Study - Sierra Leone.

In October 2014, the College of Medicine and Allied Health Sciences of the University of Sierra Leone, the Sierra Leone Ministry of Health and Sanitation, and CDC joined the global effort to accelerate assessment and availability of candidate Ebola vaccines and began planning for the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE). STRIVE was an individually randomized controlled phase II/III trial to evaluate efficacy, immunogenicity, and safety of the recombinant vesicular stomatitis virus Ebola vaccine (rVSV-ZEBOV). The study population was health care and frontline workers in select chiefdoms of the five most affected districts in Sierra Leone.

Towards host-directed therapies for tuberculosis.

The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies.

Prednisolone and Mycobacterium indicus pranii in tuberculous pericarditis.

Background: Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis.

Methods: Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M.

Rationale and design of the Investigation of the Management of Pericarditis (IMPI) trial: a 2 × 2 factorial randomized double-blind multicenter trial of adjunctive prednisolone and Mycobacterium w immunotherapy in tuberculous pericarditis.

Background: In spite of antituberculosis chemotherapy, tuberculous (TB) pericarditis causes death or disability in nearly half of those affected. Attenuation of the inflammatory response in TB pericarditis may improve outcome by reducing cardiac tamponade and pericardial constriction, but there is uncertainty as to whether adjunctive immunomodulation with corticosteroids and Mycobacterium w (M. w) can safely reduce mortality and morbidity.

Lessons from the cow: what the ruminant animal can teach us about consolidated bioprocessing of cellulosic biomass.

Consolidated bioprocessing (CBP) of cellulosic biomass is a promising source of ethanol. This process uses anaerobic bacteria, their own cellulolytic enzymes and fermentation pathways that convert the products of cellulose hydrolysis to ethanol in a single reactor. However, the engineering and economics of the process remain questionable.

Bovicin HC5 inhibits wasteful amino acid degradation by mixed ruminal bacteria in vitro.

Streptococcus bovis HC5 produces a broad spectrum lantibiotic (bovicin HC5) that inhibits pure cultures of hyper ammonia-producing bacteria (HAB). Experiments were preformed to see if: (1) S. bovis HC5 cells could inhibit the deamination of amino acids by mixed ruminal bacteria taken directly from a cow, (2) semi-purified bovicin was as effective as S.

The ability of non-bacteriocin producing Streptococcus bovis strains to bind and transfer bovicin HC5 to other sensitive bacteria.

Streptococcus bovis HC5 produces a broad spectrum lantibiotic (bovicin HC5), but S. bovis JB1 does not have antimicrobial activity. Preliminary experiments revealed an anomaly.

Quantitative analysis of cellulose degradation and growth of cellulolytic bacteria in the rumen.

Ruminant animals digest cellulose via a symbiotic relationship with ruminal microorganisms. Because feedstuffs only remain in the rumen for a short time, the rate of cellulose digestion must be very rapid. This speed is facilitated by rumination, a process that returns food to the mouth to be rechewed.

The activity and stability of cell-associated activity of bovicin HC5, a bacteriocin from Streptococcus bovis HC5.

Streptococcus bovis HC5 cultures released a broad spectrum lantibiotic, bovicin HC5, into the cell-fee culture supernatant after they reached stationary phase, but most of the antibacterial activity remained cell-associated. Cell-associated bovicin HC5 was more resistant to degradation by Pronase E than the cell-free activity. Acidic NaCl (pH 2.

Bovicin HC5, a lantibiotic produced by Streptococcus bovis HC5, catalyzes the efflux of intracellular potassium but not ATP.

Bovicin HC5, a broad-spectrum lantibiotic produced by Streptococcus bovis HC5, catalyzed the efflux of intracellular potassium from Streptococcus bovis JB1, a sensitive strain. The level of ATP also decreased, but this decline appeared to be caused by the activity of the F(1)F(0) ATPase rather than efflux per se.

The energy spilling reactions of bacteria and other organisms.

For many years it was assumed that living organisms always utilized ATP in a highly efficient manner, but simple growth studies with bacteria indicated that the efficiency of biomass production was often at least 3-fold lower than the amount that would be predicted from standard biosynthetic pathways. The utilization of energy for maintenance could only explain a small portion of this discrepancy particularly when the growth rate was high. These ideas and thermodynamic arguments indicated that cells might have another avenue of energy utilization.

Characterization of a family 45 glycosyl hydrolase from Fibrobacter succinogenes S85.

Fibrobacter succinogenes is one of the most active cellulolytic bacteria ever isolated from the rumen, but enzymes from F. succinogenes capable of hydrolyzing native (insoluble) cellulose at a rapid rate have not been identified. However, the genome sequence of F.

Effect of acidic pH on the ability of Clostridium sporogenes MD1 to take up and retain intracellular potassium.

At pH values >5.5, Clostridium sporogenes MD1 accumulated potassium even though it had little protonmotive force, but an ATPase inhibitor (N, N'- dicyclohexylcarbodiimide) prevented this uptake. The results suggested that potassium transport was ATP-driven, and a protonophore (3, 3', 4', 5 - tetrachlorosalicylanilide) did not eliminate uptake.

Bacterial competition between a bacteriocin-producing and a bacteriocin-negative strain of Streptococcus bovis in batch and continuous culture.

A bacteriocin-producing Streptococcus bovis strain (HC5) outcompeted a sensitive strain (JB1) before it reached stationary phase (pH 6.4), even though it grew 10% slower and cell-free bovicin HC5 could not yet be detected. The success of bacteriocin-negative S.

The effect of calcium and magnesium on the activity of bovicin HC5 and nisin.

Some Gram-positive bacteria produce small peptides (bacteriocins) that have antimicrobial activity, but many bacteria can become bacteriocin resistant. Bovicin HC5, a lantibiotic produced by Streptococcus bovis HC5, has the ability to inhibit nisin-resistant bacteria. Because nisin resistance has in many cases been correlated with an alteration of lipoteichoic acids or the polar head groups of membrane phospholipids, we decided to examine the effect of divalent cations on nisin and bovicin HC5 activity.

Fermentation acids inhibit amino acid deamination by Clostridium sporogenes MD1 via a mechanism involving a decline in intracellular glutamate rather than protonmotive force.

Fermentation acids inhibited the growth and ammonia production of the amino-acid-fermenting bacterium Clostridium sporogenes MD1, but only when the pH was acidic. Such inhibition was traditionally explained by the ability of fermentation acids to act as uncouplers and decrease protonmotive force (Deltap), but C. sporogenes MD1 grows even if the Deltap is very low.

Enrichment of fusobacteria from the rumen that can utilize lysine as an energy source for growth.

Ruminal lysine degradation is a wasteful process that deprives the animal of an essential amino acid. Mixed ruminal bacteria did not deaminate lysine (50 mM) at a rapid rate, but lysine degrading bacteria could be enriched if Trypticase (5 mg/mL) was also added. Lysine degrading isolates produced acetate, butyrate and ammonia, were non-motile, stained Gram-negative and could also utilize lactate, glucose, maltose or galactose as an energy source for growth.

Factors affecting lysine degradation by ruminal fusobacteria.

Fusobacterium necrophorum can readily be enriched from the rumen with lysine, and its deamination rate is very rapid. The addition of F. necrophorum JB2 to mixed ruminal bacteria significantly increased lysine degradation, but only if the ratio of ruminal fluid to basal medium was less than 25%.

The ability of acidic pH, growth inhibitors, and glucose to increase the proton motive force and energy spilling of amino acid-fermenting Clostridium sporogenes MD1 cultures.

Clostridium sporogenes MD1 grew rapidly with peptides and amino acids as an energy source at pH 6.7. However, the proton motive force (Deltap) was only -25 mV, and protonophores did not inhibit growth.

Transcriptional regulation of beta-glucanase activity in the ruminal bacterium, Prevotella bryantii B14.

The ruminal bacterium, Prevotella bryantii B(1)4, grew more rapidly with glucose as an energy source than mannose (0.73 versus 0.47 h(-1)) and had 8-fold less beta-glucanase activity (50 versus 400 nmol reducing sugar mg protein(-1) min(-1)).

Nutritional requirements of Allisonella histaminiformans, a ruminal bacterium that decarboxylates histidine and produces histamine.

Histamine is an inflammatory agent that contributes to bovine laminitis. Cattle fed silage-containing rations often have large populations of Allisonella histaminiformans, but this obligate histidine-decarboxylating bacterium could not be isolated from cattle fed timothy hay. The growth of A.

The effect of cellobiose, glucose, and cellulose on the survival of Fibrobacter succinogenes A3C cultures grown under ammonia limitation.

The ruminal, cellulolytic bacterium, Fibrobacter succinogenes A3C, grew rapidly on cellulose, cellobiose, or glucose, but it could not withstand long periods of energy source starvation. If ammonia was limiting and either cellobiose or glucose was in excess, the viability declined even faster. The carbohydrate-excess, ammonia-limited cultures did not spill energy, but they accumulated large amounts of cellular polysaccharide.

Effect of pH on the activity of bovicin HC5, a bacteriocin from Streptococcus bovis HC5.

The bacteriocin, bovicin HC5, catalyzed potassium efflux from Streptococcus bovis JB1, and this activity was highly pH dependent. When the pH was near neutral, glucose-energized cells were not affected by bovicin HC5, but the intracellular steady-state concentration of potassium decreased at acidic pH values. The idea that pH was affecting bovicin HC5 binding was supported by the observation that acidic pH also enhanced the efflux of potassium from non-energized cells that had been loaded with potassium.