Safety and immunogenicity of a next-generation live-attenuated yellow fever vaccine produced in a Vero cell line in the USA: a phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial.

Background: Recent outbreaks between 2015-17 and production delays have led to a yellow fever vaccine shortage. Therefore, there is an urgent need for new yellow fever vaccines with improved production scalability. A next-generation live-attenuated yellow fever vaccine candidate (vYF), produced in a Vero cell line has shown similar immunogenicity to licensed yellow fever vaccines in preclinical studies.

Safety and immunogenicity of a variant-adapted SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant as a booster in adults primed with authorized vaccines: a phase 3, parallel-group study.

Background: In a parallel-group, international, phase 3 study (ClinicalTrials.govNCT04762680), we evaluated prototype (D614) and Beta (B.1.

Developmental outcomes in children exposed to Zika virus in utero from a Brazilian urban slum cohort study.

Background: The prevalence of developmental alterations associated with in-utero Zika virus (ZIKV) exposure in children is not well understood. Furthermore, estimation of the Population Attributable Fraction (PAF) of developmental alterations attributed to ZIKV has not been performed due to lack of population-based cohorts with data on symptomatic and asymptomatic ZIKV exposures and an appropriate control group. The aim of this study was to characterize neurodevelopmental outcomes of children at 11 to 32 months of age with intrauterine ZIKV exposure and estimate the PAF of alterations secondary to ZIKV exposure.

A live attenuated-vaccine model confers cross-protective immunity against different species of the Leptospira genus.

Leptospirosis is the leading zoonotic disease in terms of morbidity and mortality worldwide. Effective prevention is urgently needed as the drivers of disease transmission continue to intensify. The key challenge has been developing a widely applicable vaccine that protects against the >300 serovars that can cause leptospirosis.

Risk of Sexually Transmitted Zika Virus in a Cohort of Economically Disadvantaged Urban Residents.

To understand the disease burden of sexually transmitted Zika virus (ZIKV), we prospectively followed a cohort of 359 adult and adolescent residents of an urban community in Salvador, Brazil, through the 2015 ZIKV epidemic. Later, in 2017, we used a retrospective survey to associate sexual behavior during the epidemic with ZIKV infection as defined by immunoglobulin G3 NS1 enzyme-linked immunosorbent assay. We found that males who engaged in casual sexual encounters during the epidemic were more likely (adjusted odds ratio, 6.

A respiratory syncytial virus (RSV) F protein nanoparticle vaccine focuses antibody responses to a conserved neutralization domain.

A stabilized form of the respiratory syncytial virus (RSV) fusion (F) protein has been explored as a vaccine to prevent viral infection because it presents several potent neutralizing epitopes. Here, we used a structure-based rational design to optimize antigen presentation and focus antibody (Ab) responses to key epitopes on the pre-fusion (pre-F) protein. This protein was fused to ferritin nanoparticles (pre-F-NP) and modified with glycans to mask nonneutralizing or poorly neutralizing epitopes to further focus the Ab response.

Impact of preexisting dengue immunity on Zika virus emergence in a dengue endemic region.

The clinical outcomes associated with Zika virus (ZIKV) in the Americas have been well documented, but other aspects of the pandemic, such as attack rates and risk factors, are poorly understood. We prospectively followed a cohort of 1453 urban residents in Salvador, Brazil, and, using an assay that measured immunoglobulin G3 (IgG3) responses against ZIKV NS1 antigen, we estimated that 73% of individuals were infected during the 2015 outbreak. Attack rates were spatially heterogeneous, varying by a factor of 3 within a community spanning 0.

Genomic Comparison Among Global Isolates of Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an Indel.

Leptospirosis is a worldwide zoonosis, responsible for more than 1 million cases and 60,000 deaths every year. Among the 13 pathogenic species of the genus , serovars belonging to serogroup Icterohaemorrhagiae are considered to be the most virulent strains, and responsible for majority of the reported severe cases. Serovars Copenhageni and Icterohaemorrhagiae are major representatives of this serogroup and despite their public health relevance, little is known regarding the genetic differences between these two serovars.

Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic .

Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of . In our comprehensive genomic analysis of 20 spp.

What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira.

Leptospirosis, caused by spirochetes of the genus Leptospira, is a globally widespread, neglected and emerging zoonotic disease. While whole genome analysis of individual pathogenic, intermediately pathogenic and saprophytic Leptospira species has been reported, comprehensive cross-species genomic comparison of all known species of infectious and non-infectious Leptospira, with the goal of identifying genes related to pathogenesis and mammalian host adaptation, remains a key gap in the field. Infectious Leptospira, comprised of pathogenic and intermediately pathogenic Leptospira, evolutionarily diverged from non-infectious, saprophytic Leptospira, as demonstrated by the following computational biology analyses: 1) the definitive taxonomy and evolutionary relatedness among all known Leptospira species; 2) genomically-predicted metabolic reconstructions that indicate novel adaptation of infectious Leptospira to mammals, including sialic acid biosynthesis, pathogen-specific porphyrin metabolism and the first-time demonstration of cobalamin (B12) autotrophy as a bacterial virulence factor; 3) CRISPR/Cas systems demonstrated only to be present in pathogenic Leptospira, suggesting a potential mechanism for this clade's refractoriness to gene targeting; 4) finding Leptospira pathogen-specific specialized protein secretion systems; 5) novel virulence-related genes/gene families such as the Virulence Modifying (VM) (PF07598 paralogs) proteins and pathogen-specific adhesins; 6) discovery of novel, pathogen-specific protein modification and secretion mechanisms including unique lipoprotein signal peptide motifs, Sec-independent twin arginine protein secretion motifs, and the absence of certain canonical signal recognition particle proteins from all Leptospira; and 7) and demonstration of infectious Leptospira-specific signal-responsive gene expression, motility and chemotaxis systems.

Expression and functional characterisation of TNC, a high-affinity nickel transporter from Neurospora crassa.

Our previous in silico studies identified a high-affinity nickel transporter, TNC, from the metal transportome of Neurospora crassa. A knockout mutant of the tnc gene in N. crassa failed to transport nickel, showed phenotypic growth defects and diminished urease activity under physiological levels of nickel.

Characterization of Ctr family genes and the elucidation of their role in the life cycle of Neurospora crassa.

Transcriptional analysis using qRT-PCR of 62 metal ion transporters during conidial germination of Neurospora crassa showed a significant up regulation of a hypothetical copper transporter gene, tcu-1, that belongs to the Ctr family. Herein we characterised the Ctr family genes (tcu-1, tcu-2 and tcu-3) and deciphered their role in various developmental phases of the N. crassa life cycle.

MrdH, a novel metal resistance determinant of Pseudomonas putida KT2440, is flanked by metal-inducible mobile genetic elements.

We report here the identification and characterization of mrdH, a novel chromosomal metal resistance determinant, located in the genomic island 55 of Pseudomonas putida KT2440. It encodes for MrdH, a predicted protein of approximately 40 kDa with a chimeric domain organization derived from the RcnA and RND (for resistance-nodulation-cell division) metal efflux proteins. The metal resistance function of mrdH was identified by the ability to confer nickel resistance upon its complementation into rcnA mutant (a nickel- and cobalt-sensitive mutant) of Escherichia coli.

Functional characterization of tzn1 and tzn2-zinc transporter genes in Neurospora crassa.

Previous work from our laboratory involved the description of the Neurospora metal transportome, which included seven hypothetical zinc transporters belonging to the ZIP family. The aim of the present study was to make a comparative functional evaluation of two hypothetical zinc transporters named tzn1 (NCU07621.3) and tzn2 (NCU11414.

A comparative analysis of metal transportomes from metabolically versatile Pseudomonas.

Background: The availability of complete genome sequences of versatile Pseudomonas occupying remarkably diverse ecological niches enabled to gain insights into their adaptative assets. The objective of this study was to analyze the complete genetic repertoires of metal transporters (metal transportomes) from four representative Pseudomonas species and to identify metal transporters with "Genomic Island" associated features.

Methods: A comparative metal transporter inventory was built for the following four Pseudomonas species: P.