Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine.

As SARS-CoV-2 evolves, increasing in potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.

Randomized trial showing persistence of hSBA titers elicited by a pentavalent meningococcal MenABCWY vaccine for up to 4 years following a primary series and safety and immunogenicity of a booster dose.

Background: Vaccination against 5 prominent meningococcal serogroups (A/B/C/W/Y) is necessary for broad disease protection. We report immunopersistence through 4 years after a 2-dose (6-month interval) pentavalent MenABCWY primary vaccine series and safety and immunogenicity of a booster administered 4 years after primary vaccination.

Methods: This randomized, active-controlled, observer-blinded study was conducted in the United States and Europe.

Adolescent social anxiety is associated with diminished discrimination of anticipated threat and safety in the bed nucleus of the stria terminalis.

Social anxiety-which typically emerges in adolescence-lies on a continuum and, when extreme, can be devastating. Socially anxious individuals are prone to heightened fear, anxiety, and the avoidance of contexts associated with potential social scrutiny. Yet most neuroimaging research has focused on acute social threat.

Dimensions of childhood adversity differentially affect autonomic nervous system coordination in response to stress.

It is well-established that disrupted autonomic nervous system (ANS) reactivity exacerbates risk for long-term maladjustment following childhood adversity (CA). However, few studies have integrated measures of both the sympathetic (SNS) and parasympathetic (PNS) branches of the ANS, resulting in a unidimensional understanding of ANS functioning as a mechanism of risk. Further, past work has primarily measured CA only at the aggregate level (e.

Factor H binding protein (FHbp): An evaluation of genotypic diversity across serogroups.

serogroups A, B, C, W, X, and Y cause invasive meningococcal disease (IMD) worldwide. Factor H binding protein (FHbp), a key meningococcal virulence factor, is an antigen included in both licensed meningococcal serogroup B (MenB) vaccines. This review examines the biology and epidemiology of FHbp and assesses the ability and potential of FHbp vaccine antigens to protect against IMD.

Parental Depression Symptoms, Skin Conductance Level Reactivity and Parenting: Associations with Youth Psychopathology.

Parental depression symptoms are a prevalent risk factor for internalizing and externalizing problems in youth, with parenting and parents' physiological stress reactivity representing potential contributing factors in the intergenerational transmission of psychopathology symptoms. In a sample of adolescents (N = 97) and their parents, the current study examined parental depression symptoms, an observational measure of parenting, and parents' physiological reactivity during a dyadic conflict discussion task in association with adolescents' internalizing and externalizing psychopathology. Parental depression symptoms and harsh/insensitive parenting showed positive associations with youth psychopathology symptoms.

Preclinical immunogenicity and safety of hemagglutinin-encoding modRNA influenza vaccines.

Seasonal epidemics of influenza viruses are responsible for a significant global public health burden. Vaccination remains the most effective way to prevent infection; however, due to the persistence of antigenic drift, vaccines must be updated annually. The selection of vaccine strains occurs months in advance of the influenza season to allow adequate time for production in eggs.

Neuroticism Is Prospectively Associated With 30-Month Changes in Broadband Internalizing Symptoms, but Not Narrowband Positive Affect or Anxious Arousal, in Emerging Adulthood.

Elevated levels of Neuroticism/Negative Emotionality (N/NE) and, less consistently, lower levels of Extraversion/Positive Emotionality (E/PE) confer risk for pathological depression and anxiety. To date, most prospective-longitudinal research has narrowly focused on traditional diagnostic categories, creating uncertainty about the precise nature of these prospective associations. Adopting an explicitly hierarchical-dimensional approach, we examined the association between baseline variation in personality and longitudinal changes in broad and narrow internalizing-symptom dimensions in 234 emerging adults followed for 2.

A cynomolgus monkey urinary tract infection model confirms efficacy of new FimH vaccine candidates.

The increase in urinary tract infections (UTI) caused by antibiotic-resistant requires the development of new therapeutic agents and prophylactic vaccines. To evaluate the efficacy of new lead candidates, we implemented a cynomolgus macaque UTI challenge model that mimics human uncomplicated cystitis in response to transurethral challenge with a multidrug-resistant (MDR) serotype O25b ST131 isolate. fimbrial adhesin FimH and O-antigens are separately under clinical evaluation by others as vaccine candidates to prevent UTI and invasive urosepsis disease, respectively.

Preclinical Evidence for the Protective Capacity of Antibodies Induced by Lyme Vaccine Candidate VLA15 in People.

Background: Vaccine candidate VLA15 is designed to protect against the dominant genospecies-causing Lyme disease in North America and Europe. Active immunization with VLA15 has protected in the mouse model of tick challenge. VLA15 is currently under evaluation in clinical studies for the prevention of Lyme borreliosis.

CLOVER (CLOstridium difficile Vaccine Efficacy tRial) Study: A Phase 3, Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection.

Background: Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.

Methods: This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months).

Momentary autonomic engagement during parent-adolescent conflict: Coping as a moderator of associations with emotions.

Regulatory efforts are hypothesized to affect associations between emotions and physiology (i.e., concordance) to facilitate adaptive functioning.

Nirmatrelvir and molnupiravir maintain potent in vitro and in vivo antiviral activity against circulating SARS-CoV-2 omicron subvariants.

Variants of SARS-CoV-2 pose significant challenges in public health due to their increased transmissibility and ability to evade natural immunity, vaccine protection, and monoclonal antibody therapeutics. The emergence of the highly transmissible Omicron variant and subsequent subvariants, characterized by an extensive array of over 32 mutations within the spike protein, intensifies concerns regarding vaccine evasion. In response, multiple antiviral therapeutics have received FDA emergency use approval, targeting the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and main protease (Mpro) regions, known to have relatively fewer mutations across novel variants.

Immunogenicity of the Monovalent Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine against XBB.1.5, BA.2.86, and JN.1 Sublineages: A Phase 2/3 Trial.

We report neutralization titer data against contemporary SARS-CoV-2 sublineages from an ongoing, phase 2/3, open-label, clinical trial of a single dose (30 μg) of an Omicron XBB.1.5-adapted BNT162b2 monovalent mRNA vaccine.

In vitro selection and analysis of SARS-CoV-2 nirmatrelvir resistance mutations contributing to clinical virus resistance surveillance.

To facilitate the detection and management of potential clinical antiviral resistance, in vitro selection of drug-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) against the virus M inhibitor nirmatrelvir (Paxlovid active component) was conducted. Six M mutation patterns containing T304I alone or in combination with T21I, L50F, T135I, S144A, or A173V emerged, with A173V+T304I and T21I+S144A+T304I mutations showing >20-fold resistance each. Biochemical analyses indicated inhibition constant shifts aligned to antiviral results, with S144A and A173V each markedly reducing nirmatrelvir inhibition and M activity.

A shared threat-anticipation circuit is dynamically engaged at different moments by certain and uncertain threat.

Temporal dynamics play a central role in models of emotion: is widely conceptualized as a phasic response to certain-and-imminent danger, whereas is a sustained response to uncertain-or-distal harm. Yet the underlying neurobiology remains contentious. Leveraging a translationally relevant fMRI paradigm and theory-driven modeling approach, we demonstrate that certain- and uncertain-threat anticipation recruit a shared circuit that encompasses the central extended amygdala (EAc), periaqueductal gray, midcingulate, and anterior insula.

Neuroticism/Negative Emotionality Is Associated with Increased Reactivity to Uncertain Threat in the Bed Nucleus of the Stria Terminalis, Not the Amygdala.

Neuroticism/negative emotionality (N/NE)-the tendency to experience anxiety, fear, and other negative emotions-is a fundamental dimension of temperament with profound consequences for health, wealth, and well-being. Elevated N/NE is associated with a panoply of adverse outcomes, from reduced socioeconomic attainment to psychiatric illness. Animal research suggests that N/NE reflects heightened reactivity to uncertain threat in the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce), but the relevance of these discoveries to humans has remained unclear.

Bivalent Omicron BA.4/BA.5 BNT162b2 Vaccine in 6-Month- to <12-Year-Olds.

Background: With the future epidemiology and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uncertain, the use of safe and effective coronavirus disease 2019 (COVID-19) vaccines in pediatric populations remains important.

Methods: We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating the safety and immunogenicity of a variant-adapted bivalent COVID-19 vaccine encoding ancestral and Omicron BA.4/BA.

Adolescent social anxiety is associated with diminished discrimination of anticipated threat and safety in the bed nucleus of the stria terminalis.

Social anxiety-which typically emerges in adolescence-lies on a continuum and, when extreme, can be devastating. Socially anxious individuals are prone to heightened fear, anxiety, and the avoidance of contexts associated with potential social scrutiny. Yet most neuroimaging research has focused on acute social threat.

Development of a sequence-based OspA typing method for .

Lyme disease (LD), caused by spirochete bacteria of the genus , remains the most common vector-borne disease in the northern hemisphere. outer surface protein A (OspA) is an integral surface protein expressed during the tick cycle, and a validated vaccine target. There are at least 20 recognized genospecies, that vary in OspA serotype.

Effectiveness and cost-effectiveness of a 12-month automated text message intervention for weight management in postpartum women with overweight or obesity: protocol for the Supporting MumS (SMS) multisite, parallel-group, randomised controlled trial.

Introduction: The reproductive years can increase women's weight-related risk. Evidence for effective postpartum weight management interventions is lacking and engaging women during this life stage is challenging. Following a promising pilot evaluation of the Supporting MumS intervention, we assess if theory-based and bidirectional text messages to support diet and physical activity behaviour change for weight loss and weight loss maintenance, are effective and cost-effective for weight change in postpartum women with overweight or obesity, compared with an active control arm receiving text messages on child health and development.