Contributions of humoral and cellular immunity to vaccine-induced protection in humans

AbstractVaccines play a vital role in protecting the host against infectious disease. The most effective licensed vaccines elicit long-term antigen-specific antibody responses by plasma cells in addition to the development of persisting T cell and B cell memory. The relative contributions of these different immune cell subsets are context-dependent and vary depending on the attributes of the vaccine (i.e., live/attenuated, inactivated, and subunit) as well as the biology of the pathogen in question. For relatively simple vaccines against bacterial antigens (e.g., tetanus toxin) or invariant viruses, the immunological correlates of protection are well-characterized. For more complex vaccines against viruses, especially those that mutate or cause latent infections, it is more difficult to define the specific correlates of immunity. This often requires observational/natural history studies, clinical trials, or experimental evaluation in relevant animal models in order for immunological correlates to be determined or extrapolated. In this review, we will discuss the relative contributions of virus-specific T cell and B cell responses to vaccine-mediated protection against disease

A qualitative evaluation of occupational therapy-led work rehabilitation for people with inflammatory arthritis : perspectives of therapists and their line managers

Introduction: Occupational therapy-led work rehabilitation for employed people with inflammatory arthritis and work problems was piloted in five hospitals in the United Kingdom. This qualitative study explored the views of participating occupational therapists and their line managers about the work rehabilitation training received and conducting the intervention, with particular focus on the structured interview used, the Work Experience Survey – Rheumatic Conditions. Method: Face-to-face semi-structured interviews were conducted with occupational therapists (n¼9), followed by telephone interviews with their line managers (n¼2). Interviews were audio-recorded, transcribed verbatim and thematically analysed by three researchers to maximize validity. Results: The main themes emerging from the occupational therapists’ interviews were: varying levels of prior knowledge and experience of work rehabilitation, initial concerns about the feasibility of a lengthy work assessment in practice and increased confidence in delivering work rehabilitation as the study progressed. The line managers’ interviews generated themes around the positive impact of the work rehabilitation training the occupational therapists received, and changes in their practice. Conclusion: The Work Experience Survey – Rheumatic Conditions was considered a good choice of work assessment which can be implemented in practice. Once therapists had provided the work intervention several times, their confidence and skills increase

Implantação de um modelo de gestão socialmente responsável: um estudo de caso

O presente trabalho tem por objetivo identificar as dificuldades para implantar um modelo de gestão socialmente responsável de acordo com a percepção da gerente da área da empresa participante. O estudo foi realizado em uma empresa pública de grande porte, localizada em todos os estados da federação. O estudo apresenta uma revisão dos principais conceitos e aspectos envolvendo responsabilidade social empresarial e gerência, apresenta o estudo de caso da empresa X, bem como a análise entre teoria e resultados percebidos. Utilizou-se da pesquisa bibliográfica, pesquisa documental, entrevista semi-estruturada em profundidade e aplicação de questionário como forma de coleta de dados. É discutido no estudo sobre o posicionamento do nível de gerência e diretoria sobre responsabilidade social, o alcance de metas e a prática de ações socialmente responsáveis. A principal reflexão que se faz deste estudo de caso é que existe uma diferença significante no que diz respeito às diretrizes formais da empresa e a real prática delas a respeito das questões éticas e socialmente responsáveis

Reliability of the evidence to guide decision-making in foot ulcer prevention in diabetes : an overview of systematic reviews

Funding: This overview was funded as part of a wider project by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (HTA project: 15/171/01). The views expressed are those of the authors and not necessarily those of the NIHR or UK Department of Health and Social Care.Background: Reliable evidence on the effectiveness of interventions to prevent diabetes-related foot ulceration is essential to inform clinical practice. Well-conducted systematic reviews that synthesise evidence from all relevant trials offer the most robust evidence for decision-making. We conducted an overview to assess the comprehensiveness and utility of the available secondary evidence as a reliable source of robust estimates of effect with the aim of informing a cost-effective care pathway using an economic model. Here we report the details of the overview. [PROSPERO Database (CRD42016052324)]. Methods: Medline (Ovid), Embase (Ovid), Epistomonikos, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effectiveness (DARE), and the Health Technology Assessment Journals Library were searched to 17th May 2021, without restrictions, for systematic reviews of randomised controlled trials (RCTs) of preventive interventions in people with diabetes. The primary outcomes of interest were new primary or recurrent foot ulcers. Two reviewers independently extracted data and assessed the risk of bias in the included reviews. Findings: The overview identified 30 systematic reviews of patient education, footwear and of-loading, complex and other interventions. Many are poorly reported and have fundamental methodological shortcomings associated with increased risk of bias. Most concerns relate to vague inclusion criteria (60%), weak search or selection strategies (70%) and quality appraisal methods (53%) and inexpert conduct and interpretation of quantitative and narrative evidence syntheses (57%). The 30 reviews have collectively assessed 26 largely poor-quality RCTs with substantial overlap. Interpretation: The majority of these systematic reviews of the effectiveness of interventions to prevent diabetic foot ulceration are at high risk of bias and fail to provide reliable evidence for decision-making. Adherence to the core principles of conducting and reporting systematic reviews is needed to improve the reliability of the evidence generated to inform clinical practice.Publisher PDFPeer reviewe

Pesquisa sobre Crianças como Consumidoras: Uma Discussão sobre as Formas de Conhecer e a Realidade da Pesquisa no Brasil

O interesse no comportamento das crianças no mundo do consumo tem pouco mais de 60 anos. A discussão sobre o processo de inserção e atuação da criança como consumidora ao mesmo tempo em que traz o aspecto da vulnerabilidade infantil e da moralidade das ações de marketing, é visto o crescimento da publicidade e da lucratividade do mercado kids. Embora exista a relevância e o interesse do mercado e da academia, ainda não há um conjunto significativo de conhecimento e de teorias desenvolvidas sobre consumo infantil. Sendo assim, este ensaio se propõe a discutir as formas de conhecer, ou seja, comenta sobre as epistemologias empregadas nos estudos sobre comportamento de compra infantil, e discute o status e a realidade das pesquisas brasileiras

Rheumatology occupational therapists' line managers' views of a vocational rehabilitation programme delivered to patients with work problems

Background: Before becoming work disabled people with inflammatory arthritis experience work instability, which threatens employment. Occupational therapists (OT) are well–placed to assist patients to remain at work [1]. However, many OTs in the UK lack vocational rehabilitation (VR) skills [2]. Objectives: This study, nested within a pilot VR randomised controlled trial (RCT), aimed to explore the National Health Service (NHS) OTs' line managers' views of the VR training participating OTs received as part of the trial, and whether there are any potential barriers and facilitators to delivering the VR intervention in a future trial/clinical practice. Methods: As part of the trial, Rheumatology OTs (n=9) attended three-days training in VR and the use of a structured interview: the Work Experience Survey – Rheumatic Conditions (WES-RC)[3-5]. After training and intervention delivery, semi-structured telephone interviews with these OTs' line managers were conducted, recorded, transcribed and thematically analysed by two researchers to ensure validity. Results: All five OT line managers were contacted but only two agreed to be interviewed, although both provided rich data. Two main themes emerged were: (i) the impact of the VR training received, and (ii) the positive change in OT practice. Both line managers thought the training given was comprehensive. They reported positive practice changes, for example, the WES-RC helped the OTs identify and prioritise work problems of employed people with inflammatory arthritis (IA). As result, their practice now included work assessment and the VR programme. These changes in service provision were appreciated by the Rheumatology multi-disciplinary team, which works very closely across cases. The line managers identified the VR training OTs received as the most important facilitator to delivering the VR intervention in the future, suggesting this training should extent to their line managers to help understand and manage OT's role in VR. Potential barriers to delivering an OT VR intervention in a future trial/ clinical practice were: time and financial constraints around the attendance to comprehensive training in VR. Conclusions: Rheumatology OTs' line managers acknowledged the need for training OTs in VR, and importance of providing VR to IA patients with work problems. For the OT VR service to be successful, prior training of OTs and if possible their line managers in VR delivery was deemed important by these line managers. References: J Ross (2007) John Wiley and Sons. ISBN 978-0-470-02564. Barnes et al (2009) Work. COT: London. O'Brien R et al (2013) Musculoskeletal Care 11:99-105. Allaire S & Keysor J (2009) Arthritis Care and Research 61(7):988-995. Prior Y et al (2013) Turk J of Phys Med and Rehab 59 (Suppl 2), p76. Acknowledgements: We would like to thank to occupational therapists and their line managers at the participating NHS hospitals, and Arthritis Research UK for funding this project. Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2015-eular.1998 Citation: Ann Rheum Dis2015;74(Suppl2): 1352 Session: Occupational therap

Role of Multivalency and Antigenic Threshold in Generating Protective Antibody Responses

Vaccines play a vital role in protecting our communities against infectious disease. Unfortunately, some vaccines provide only partial protection or in some cases vaccine-mediated immunity may wane rapidly, resulting in either increased susceptibility to that disease or a requirement for more booster vaccinations in order to maintain immunity above a protective level. The durability of antibody responses after infection or vaccination appears to be intrinsically determined by the structural biology of the antigen, with multivalent protein antigens often providing more long-lived immunity than monovalent antigens. This forms the basis for the Imprinted Lifespan model describing the differential survival of long-lived plasma cell populations. There are, however, exceptions to this rule with examples of highly attenuated live virus vaccines that are rapidly cleared and elicit only short-lived immunity despite the expression of multivalent surface epitopes. These exceptions have led to the concept that multivalency alone may not reliably determine the duration of protective humoral immune responses unless a minimum number of long-lived plasma cells are generated by reaching an appropriate antigenic threshold of B cell stimulation. Examples of long-term and in some cases, potentially lifelong antibody responses following immunization against human papilloma virus (HPV), Japanese encephalitis virus (JEV), Hepatitis B virus (HBV), and Hepatitis A virus (HAV) provide several lessons in understanding durable serological memory in human subjects. Moreover, studies involving influenza vaccination provide the unique opportunity to compare the durability of hemagglutinin (HA)-specific antibody titers mounted in response to antigenically repetitive whole virus (i.e., multivalent HA), or detergent-disrupted “split” virus, in comparison to the long-term immune responses induced by natural influenza infection. Here, we discuss the underlying mechanisms that may be associated with the induction of protective immunity by long-lived plasma cells and their importance in future vaccine design

A hydrogen peroxide-inactivated virus vaccine elicits humoral and cellular immunity and protects against lethal west nile virus infection in aged mice

West Nile virus (WNV) is an emerging pathogen that is now the leading cause of mosquito-borne and epidemic encephalitis in the United States. In humans, a small percentage of infected individuals develop severe neuroinvasive disease, with the greatest relative risk being in the elderly and immunocompromised, two populations that are difficult to immunize effectively with vaccines. While inactivated and subunit-based veterinary vaccines against WNV exist, currently there is no vaccine or therapy available to prevent or treat human disease. Here, we describe the generation and preclinical efficacy of a hydrogen peroxide (H(2)O(2))-inactivated WNV Kunjin strain (WNV-KUNV) vaccine as a candidate for further development. Both young and aged mice vaccinated with H(2)O(2)-inactivated WNV-KUNV produced robust adaptive B and T cell immune responses and were protected against stringent and lethal intracranial challenge with a heterologous virulent North American WNV strain. Our studies suggest that the H(2)O(2)-inactivated WNV-KUNV vaccine is safe and immunogenic and may be suitable for protection against WNV infection in vulnerable populations