Controlled Human Infection with Bordetella pertussis.

Bordetella pertussis, a slow-growing Gram-negative coccobacillus and the causative agent of whooping cough, is one of the leading causes of vaccine-preventable death and morbidity globally. A state of asymptomatic human carriage has not yet been demonstrated by population studies but is likely to be an important reservoir for community transmission of infection. Such a carriage state may be a target for future vaccine strategies.

Psychological distress experienced by parents caring for an immunosuppressed child during the COVID-19 pandemic.

The COVID-19 pandemic has proved unique in both its unpredictability and the extent to which it has continued to impact on daily life since March 2020. Among the immunosuppressed population the challenges of the COVID-19 pandemic are cumulative to the ever-present challenges of living with a long-term condition. This prospective longitudinal study explored patterns of concern experienced by 467 British parents caring for an immunosuppressed child during the first 2 years of the COVID-19 pandemic and related this to parental mental wellbeing.

Effect of colonisation with Neisseria lactamica on cross-reactive anti-meningococcal B-cell responses: a randomised, controlled, human infection trial.

Background: Pharyngeal colonisation by the commensal bacterium Neisseria lactamica inhibits colonisation by Neisseria meningitidis and has an inverse epidemiological association with meningococcal disease. The mechanisms that underpin this relationship are unclear, but could involve the induction of cross-reactive immunity. In this study, we aimed to evaluate whether colonisation with N lactamica induces N lactamica-specific B-cell responses that are cross-reactive with N meningitidis.

Parental concern for clinically vulnerable child during first 18 months of the COVID pandemic.

Background: The uncertainties surrounding the COVID-19 pandemic have been associated with increased parental concern. The aim of this study is to explore if this increased level of concern is associated with certain individual/household characteristics or if parents adapted to the ever-changing realities of the COVID-19 pandemic over time.

Methods: This prospective study explored COVID-19 concern trajectories and associated family characteristics of 765 UK parents caring for an immunosuppressed child during the first 18 months of the pandemic using growth mixture modelling.

The role of public involvement in the design of the first SARS-CoV-2 human challenge study during an evolving pandemic.

High quality health care research must involve patients and the public. This ensures research is important, relevant and acceptable to those it is designed to benefit. The world's first human challenge study with SARS-CoV-2 undertook detailed public involvement to inform study design despite the urgency to review and establish the study.

Public attitudes to a human challenge study with SARS-CoV-2: a mixed-methods study.

Human challenge studies involve the deliberate exposure of healthy volunteers to an infectious micro-organism in a highly controlled and monitored way. They are used to understand infectious diseases and have contributed to the development of vaccines. In early 2020, the UK started exploring the feasibility of establishing a human challenge study with SARS-CoV-2.

Immunocompromised children and young people are at no increased risk of severe COVID-19.

Objectives: We aimed to prospectively describe the incidence and clinical spectrum of SARS-CoV-2 infection in immunocompromised paediatric patients in the UK.

Methods: From March 2020 to 2021 weekly questionnaires were sent to immunocompromised paediatric patients or their parents. Information, including symptom presentation and SARS-CoV-2 PCR test results, was collected from 1527 participants from 46 hospitals.

Neisseria lactamica Controlled Human Infection Model.

Neisseria lactamica is a nonpathogenic commensal of the human upper respiratory tract that has been associated with protection against N. meningitidis colonization and disease. We have previously utilized the N.

Safety and Immunogenicity of ChAd63/MVA Pfs25-IMX313 in a Phase I First-in-Human Trial.

Background: Transmission blocking vaccines targeting the sexual-stages of the malaria parasite could play a major role to achieve elimination and eradication of malaria. The Pfs25 protein (Pfs25) is the most clinically advanced candidate sexual-stage antigen. IMX313, a complement inhibitor C4b-binding protein that forms heptamers with the antigen fused to it, improve antibody responses.

A recombinant commensal bacteria elicits heterologous antigen-specific immune responses during pharyngeal carriage.

The human nasopharynx contains a stable microbial ecosystem of commensal and potentially pathogenic bacteria, which can elicit protective primary and secondary immune responses. Experimental intranasal infection of human adults with the commensal produced safe, sustained pharyngeal colonization. This has potential utility as a vehicle for sustained release of antigen to the human mucosa, but commensals in general are thought to be immunologically tolerated.

COVID-19 symptom surveillance in immunocompromised children and young people in the UK: a prospective observational cohort study.

Objectives: To describe the frequency of symptoms compatible with SARS-CoV-2 infection in immunocompromised children and young people in the UK during the SARS-CoV-2 pandemic. To describe patient/parent anxiety regarding SARS-CoV-2 infection in this cohort.

Design: A prospective observational cohort study.

Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.

Background: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19 (AZD1222), in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older.

Exploring the acceptability of controlled human infection with SARSCoV2-a public consultation.

Rapid development of an effective vaccine for SARSCoV2 is a global priority. A controlled human infection model (CHIM) would accelerate the efficacy assessment of candidate vaccines. This strategy would require deliberate exposure of volunteers to SARSCoV2 with no currently available treatment and a small but definite risk of serious illness or death.

Controlled Human Infection With Bordetella pertussis Induces Asymptomatic, Immunizing Colonization.

Background: Bordetella pertussis is among the leading causes of vaccine-preventable deaths and morbidity globally. Human asymptomatic carriage as a reservoir for community transmission of infections might be a target of future vaccine strategies, but has not been demonstrated. Our objective was to demonstrate that asymptomatic nasopharyngeal carriage of Bordetella pertussis is inducible in humans and to define the microbiological and immunological features of presymptomatic infection.

Protocol for a controlled human infection with genetically modified expressing the meningococcal vaccine antigen NadA: a potent new technique for experimental medicine.

Introduction: is a commensal organism found in the human nasopharynx and is closely related to the pathogen (meningococcus). Carriage of is associated with reduced meningococcal carriage and disease. We summarise an ethically approved protocol for an experimental human challenge study using a genetically modified strain of that expresses the meningococcal antigen NadA.

Safety and efficacy of novel malaria vaccine regimens of RTS,S/AS01B alone, or with concomitant ChAd63-MVA-vectored vaccines expressing ME-TRAP.

We assessed a combination multi-stage malaria vaccine schedule in which RTS,S/AS01B was given concomitantly with viral vectors expressing multiple-epitope thrombospondin-related adhesion protein (ME-TRAP) in a 0-month, 1-month, and 2-month schedule. RTS,S/AS01B was given as either three full doses or with a fractional (1/5th) third dose. Efficacy was assessed by controlled human malaria infection (CHMI).

Antenatal vaccination against Group B streptococcus: attitudes of pregnant women and healthcare professionals in the UK towards participation in clinical trials and routine implementation.

Introduction: Maternal vaccination is increasingly part of antenatal care in the UK and worldwide. Trials of Group B streptococcus vaccines are ongoing. This study investigated the attitudes of pregnant women and healthcare professionals towards antenatal vaccination, both in routine care and a clinical trial setting.

Investigating colonisation and immunity: protocol for an inpatient controlled human infection model.

Introduction: We summarise an ethically approved protocol for the development of an experimental human challenge colonisation model. Globally is one of the leading causes of vaccine-preventable death. Many countries have replaced whole cell vaccines with acellular vaccines over the last 20 years during which pertussis appears to be resurgent in a number of countries in the developed world that boast high immunisation coverage.

Severe Enterovirus Infections in Hospitalized Children in the South of England: Clinical Phenotypes and Causative Genotypes.

Background: Most enterovirus surveillance studies lack detailed clinical data, which limits their clinical usefulness. This study aimed to describe the clinical spectrum and outcome of severe enterovirus infections in children, and to determine whether there are associations between causative enterovirus genotypes and clinical phenotypes.

Methods: Retrospective analysis of microbiological and clinical data from a tertiary children's hospital in the South of England over a 17-month period (2012-2013).