In Depth Breadth Analyses of Human Blockade Responses to Norovirus and Response to Vaccination.

To evaluate and understand the efficacy of vaccine candidates, supportive immunological measures are needed. Critical attributes for a norovirus vaccine are the strength and breadth of antibody responses against the many different genotypes. In the absence of suitable neutralization assays to test samples from vaccine clinical trials, blockade assays offer a method that can measure functional antibodies specific for many of the different norovirus strains. This paper describes development and optimization of blockade assays for an extended panel of 20 different norovirus strains that can provide robust and reliable data needed for vaccine assessment. The blockade assays were used to test a panel of human clinical samples taken before and after vaccination with the Takeda TAK-214 norovirus vaccine. Great variability was evident in the repertoire of blocking antibody responses prevaccination and postvaccination among individuals. Following vaccination with TAK-214, blocking antibody levels were enhanced across a wide spectrum of different genotypes. The results indicate that adults may have multiple exposures to norovirus and that the magnitude and breadth of the complex preexisting antibody response can be boosted and expanded by vaccination.

The role of anxiety in vaginismus: a case-control study.

INTRODUCTION: Previous research suggests that anxiety may play a large role in the symptoms of vaginismus. AIM: We aimed to (i) determine the degree of self-reported general anxiety in women with vaginismus; and (ii) establish whether general anxiety is a consequence of the condition or a predisposing factor. MAIN OUTCOME MEASURES: Participants reported state and trait anxiety, five-factor personality scores, history of anxiety disorders, and their perceptions of their symptoms and history. METHODS: We compared responses of 244 self-identified women with vaginismus with a control group of 101 women using an online questionnaire. RESULTS: The women with vaginismus were higher in trait anxiety and neuroticism, and lower in extraversion, than the controls. There was also a trend toward a greater prevalence of diagnosed anxiety disorders in the vaginismus group. Levels of state anxiety were high among the women with vaginismus, particularly when they felt unsupported by their partners or pressured to cure the condition. CONCLUSION: Levels of general anxiety are elevated among women with vaginismus and the data suggest that anxiety-proneness may be a predisposing factor for the condition. We conclude that although vaginismus is a multidimensional condition, it may have common predisposing factors with anxiety disorders.

Mycobacterium tuberculosis binding to human surfactant proteins A and D, fibronectin, and small airway epithelial cells under shear conditions.

A crucial step in infection is the initial attachment of a pathogen to host cells or tissue. Mycobacterium tuberculosis has evolved multiple strategies for establishing an infection within the host. The pulmonary microenvironment contains a complex milieu of pattern recognition molecules of the innate immune system that play a role in the primary response to inhaled pathogens. Encounters of M. tuberculosis with these recognition molecules likely influence the outcome of the bacillus-host interaction. Here we use a novel fluid shear assay to investigate the binding of M. tuberculosis to innate immune molecules that are produced by pulmonary epithelial cells and are thought to play a role in the lung innate immune response. Virulent and attenuated M. tuberculosis strains bound best to immobilized human fibronectin (FN) and surfactant protein A (SP-A) under this condition. Binding under fluid shear conditions was more consistent and significant compared to binding under static conditions. Soluble FN significantly increased the adherence of both virulent and attenuated M. tuberculosis strains to human primary small airway epithelial cells (SAEC) under fluid shear conditions. In contrast, SP-A and SP-D effects on bacterial adherence to SAEC differed between the two strains. The use of a fluid shear model to simulate physiological conditions within the lung and select for high-affinity binding interactions should prove useful for studies that investigate interactions between M. tuberculosis and host innate immune determinants.