A neutralizing human antibody induces movement of the HCoV-229E receptor binding domain.

HCoV-229E is an endemic that typically causes common cold-like disease in most healthy adults, but can also cause severe respiratory disease in the very young and the elderly. Although the virus was discovered over sixty years ago and undergoes continuous antigenic drift, remarkably little is known about the humoral immune response to HCoV-229E infection. Here we report the isolation of two receptor binding domain-targeting neutralizing human antibodies raised in response to natural HCoV-229E infection.

Determining an appropriate fosfomycin (ZTI-01) dosing regimen in pneumonia patients by utilizing minimal PBPK modeling and target attainment analysis.

Fosfomycin, a broad-spectrum antibiotic used for uncomplicated cystitis, represents a potential promising candidate in combating resistant pneumonia. To facilitate the transition of fosfomycin to broader indications, including pneumonia, a minimal physiologically based pharmacokinetics (m-PBPK) model for fosfomycin was developed based on data from plasma, epithelial lining fluid (ELF), and alveolar macrophages (AMs) obtained from 37 healthy participants in a recently completed intrapulmonary PK study. Utilizing this mechanistic m-PBPK model enabled us to predict drug concentrations at the infection site in pneumonia patients, taking into consideration the pathophysiological changes occurring during the infection.

Fluorescence-barcoded cell lines stably expressing membrane-anchored influenza neuraminidases.

The discovery of broadly protective antibodies to the influenza virus neuraminidase (NA) has raised interest in NA as a vaccine target. However, recombinant, solubilized tetrameric NA ectodomains are often challenging to express and isolate, hindering the study of anti-NA humoral responses. To address this obstacle, we established a panel of 22 non-adherent cell lines stably expressing native, historical N1, N2, N3, N9, and NB NAs anchored on the cell surface.

Rural-urban disparities in human papillomavirus vaccination: Findings from a cross-sectional survey of 13 southern US states, December 2019-January 2020.

Background: Rural adolescents in the United States lag behind their urban counterparts in the uptake of the human papillomavirus (HPV) vaccine. However, a systematic assessment of factors associated with rural-urban disparities in HPV vaccination coverage to inform potential vaccination promotion interventions is lacking in the literature. Prioritizing HPV vaccination for rural adolescents is necessary for increasing overall HPV vaccination coverage for adolescents and for reducing the incidence of HPV infections and future HPV-related cancers.

Perceived feasibility of a multicomponent prenatal intervention on childhood vaccinations: Findings from a national cross-sectional survey of prenatal care providers, April-June 2022.

Background: There are inadequate proactive interventions that take advantage of medical contacts during pregnancy to build confidence in vaccines recommended for children after birth. In addition, prenatal providers' perceptions on implementing such proactive childhood vaccination-focused interventions are not well understood.

Methods: A multicomponent prenatal intervention on childhood vaccines was designed for expectant parents to include a prenatal provider recommendation encouraging age-appropriate vaccines for children after birth, an educational website on vaccine recommendations and resources, and a phone consultation with a vaccine navigator during pregnancy.

A phase I study of the safety, reactogenicity and immunogenicity of two quadrivalent seasonal influenza vaccines (Fluzone® or Flublok®) with or without one of two adjuvants (AF03 or Advax-CpG55.2) in healthy adults 18-45 years of age.

Seasonal influenza continues to cause significant morbidity and mortality, particularly for the elderly and immunocompromised. Current licensed influenza vaccines provide only partial protection even for immunocompetent hosts. Vaccine adjuvants can improve the magnitude and breadth of immune responses and there is considerable interest in identifying new adjuvants that can improve immune responses to seasonal influenza vaccines.

Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.

Fluorescence-barcoded cell lines stably expressing membrane-anchored influenza neuraminidases.

The discovery of broadly protective antibodies to the influenza virus neuraminidase (NA) has raised interest in NA as a vaccine target. However, recombinant, solubilized tetrameric NA ectodomains are often challenging to express and isolate, hindering the study of anti-NA humoral responses. To address this obstacle, we established a panel of 22 non-adherent cell lines stably expressing native, historical N1, N2, N3, N9, and NB NAs anchored on the cell surface.

Evaluation of the safety profile and intrapulmonary pharmacokinetics of intravenous fosfomycin in healthy adults.

Unlabelled: This Phase 1 trial described the intrapulmonary pharmacokinetics and safety profile of IV fosfomycin in healthy participants Fosfomycin, a broad-spectrum antibiotic mainly used to treat urinary tract infections, is being considered for treatment of more complex conditions, including lung infections, due to the emergence of multidrug-resistant (MDR) organisms. Despite its potential, the pharmacokinetics and safety profile of intravenous (IV) fosfomycin, particularly its penetration into the lower respiratory tract, are unknown. To address this gap, we conducted a Phase 1, open-label trial to assess the safety and pulmonary pharmacokinetics of IV fosfomycin in healthy participants.

Influenza vaccine effectiveness against medically attended outpatient illness, United States, 2023-24 season.

Background: The 2023-24 U.S. influenza season was characterized by a predominance of A(H1N1)pdm09 virus circulation with co-circulation of A(H3N2) and B/Victoria viruses.

Apnea After 2-Month Vaccinations in Hospitalized Preterm Infants: A Randomized Clinical Trial.

Importance: Preterm infants are recommended to receive most vaccinations at the same postnatal age as term infants. Studies have inconsistently observed an increased risk for postvaccination apnea in preterm infants.

Objective: To compare the proportions of hospitalized preterm infants with apnea and other adverse events in the 48 hours after 2-month vaccinations vs after no vaccinations.

Population Pharmacokinetics of Meropenem Across the Adult Lifespan.

Background And Objective: We conducted an opportunistic pharmacokinetic study to evaluate the population pharmacokinetics of meropenem, an antimicrobial commonly used to treat Gram-negative infections in adults of different ages, including older adults, and determined optimal dosing regimens.

Methods: A total of 99 patients were included. The population pharmacokinetic models used had two compartments: zero-order input and linear elimination.

New Approaches to Respiratory Syncytial Virus Prevention and Treatment.

There have been several recent advances in the prevention of lower respiratory tract disease (LRTD) due to respiratory syncytial virus (RSV) infection in older adults and young children. Three different vaccines are now approved for use in older adults; one of these vaccines is also approved for use in pregnant individuals for the prevention of LRTD due to RSV in their infants. In addition, a new monoclonal antibody is available to prevent RSV LRTD in infants born during or entering their first RSV season and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.

Influenza vaccine effectiveness against medically attended outpatient illness, United States, 2023-24 season.

Background: The 2023-24 U.S. influenza season was characterized by a predominance of A(H1N1)pdm09 virus circulation with co-circulation of A(H3N2) and B/Victoria viruses.

An ADaptivE PrenaTal (ADEPT) intervention to increase childhood vaccinations: Protocol for a cluster randomized trial and nested mixed methods evaluation.

Background: There is limited evidence to assess if interventions implemented during pregnancy proactively mitigate parental vaccine hesitancy and promote timely vaccination among children after birth. This study protocol describes the evaluation of an ADaptivE PrenaTal (ADEPT) intervention to increase childhood vaccinations that is implemented with first-time pregnant individuals (PIs).

Methods: Within the framework of a type 1 effectiveness-implementation hybrid study design, a cluster-randomized trial (CRT) will determine the effectiveness of ADEPT at increasing childhood vaccinations, and a nested explanatory mixed methods (NMM) study will assess changes in parental vaccine hesitancy.

Safety of Simultaneous vs Sequential mRNA COVID-19 and Inactivated Influenza Vaccines: A Randomized Clinical Trial.

Importance: Limited randomized clinical trial data exist on the safety of simultaneous administration of COVID-19 and influenza vaccines.

Objective: To compare the reactogenicity, safety, and changes in health-related quality of life (HRQOL) after simultaneous vs sequential receipt of messenger RNA (mRNA) COVID-19 vaccine and quadrivalent inactivated influenza vaccine (IIV4).

Design, Setting, And Participants: This randomized, placebo-controlled clinical trial was conducted between October 8, 2021, and June 14, 2023, at 3 US sites.

Safety of Simultaneous Vaccination With Adjuvanted Zoster Vaccine and Adjuvanted Influenza Vaccine: A Randomized Clinical Trial.

Importance: Quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) and adjuvanted recombinant zoster vaccine (RZV) contain novel adjuvants. Data are limited on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of the simultaneous administration of these vaccines.

Objective: To compare the safety and reactogenicity after simultaneous doses of RZV and aIIV4 administration (opposite arms) with simultaneous doses of RZV with quadrivalent high-dose inactivated influenza vaccine [HD-IIV4]).

Late-Season Influenza Vaccine Effectiveness Against Medically Attended Outpatient Illness, United States, December 2022-April 2023.

Background: The 2022-23 US influenza season peaked early in fall 2022.

Methods: Late-season influenza vaccine effectiveness (VE) against outpatient, laboratory-confirmed influenza was calculated among participants of the US Influenza VE Network using a test-negative design.

Results: Of 2561 participants enrolled from December 12, 2022 to April 30, 2023, 91 laboratory-confirmed influenza cases primarily had A(H1N1)pdm09 (6B.

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.

A chimeric haemagglutinin-based universal influenza virus vaccine boosts human cellular immune responses directed towards the conserved haemagglutinin stalk domain and the viral nucleoprotein.

Background: The development of a universal influenza virus vaccine, to protect against both seasonal and pandemic influenza A viruses, is a long-standing public health goal. The conserved stalk domain of haemagglutinin (HA) is a promising vaccine target. However, the stalk is immunosubdominant.

Geographic Progression of Infant Respiratory Syncytial Virus Associated Bronchiolitis Across the United States Before and Since the Onset of COVID-19: Results From Four Health Systems, 2015-2023.

Background: Respiratory syncytial virus (RSV) is a substantial cause of infant morbidity and mortality due to seasonal peaks of bronchiolitis across the United States. Clinical and viral surveillance plays a pivotal role in helping hospital systems prepare for expected surges in RSV bronchiolitis. Existing surveillance efforts have shown a geographic pattern of RSV positivity across the United States, with cases typically starting in the southeast and spreading north and west.

A Phase 2 Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Prime-Boost Vaccination Schedules of 2013 and 2017 A(H7N9) Inactivated Influenza Virus Vaccines Administered With and Without AS03 Adjuvant in Healthy US Adults.

Introduction: A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs.

Methods: Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial.