Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
169
result(s) for
"Tanner, Rachel"
Sort by:
The Humoral Immune Response to BCG Vaccination
Bacillus Calmette Guérin (BCG) is the only currently available vaccine against tuberculosis (TB), but it confers incomplete and variable protection against pulmonary TB in humans and bovine TB (bTB) in cattle. Insights into the immune response induced by BCG offer an underexploited opportunity to gain knowledge that may inform the design of a more efficacious vaccine, which is urgently needed to control these major global epidemics. Humoral immunity in TB and bTB has been neglected, but recent studies supporting a role for antibodies in protection against TB has driven a growing interest in determining their relevance to vaccine development. In this manuscript we review what is known about the humoral immune response to BCG vaccination and re-vaccination across species, including evidence for the induction of specific B cells and antibodies; and how these may relate to protection from TB or bTB. We discuss potential explanations for often conflicting findings and consider how factors such as BCG strain, manufacturing methodology and route of administration influence the humoral response. As novel vaccination strategies include BCG prime-boost regimens, the literature regarding off-target immunomodulatory effects of BCG vaccination on non-specific humoral immunity is also reviewed. Overall, reported outcomes to date are inconsistent, but indicate that humoral responses are heterogeneous and may play different roles in different species, populations, or individual hosts. Further study is warranted to determine whether a new TB vaccine could benefit from the targeting of humoral as well as cell-mediated immunity.
Journal Article
Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review
BCG vaccination can have heterologous or non-specific effects (NSE) that confer resistance against pathogens other than its target Mycobacterium tuberculosis, but the underlying mechanisms are not fully understood.
We conducted a systematic review synthesising existing literature on immune mechanisms mediating the heterologous/NSE of BCG. Searches were conducted using MEDLINE and Scopus.
1032 original records were identified, of which 67 were deemed eligible. Several potentially relevant immune pathways were identified, although there may be variation by pathogen. Recent studies have focused on trained immunity whereby innate cells, or the hematopoietic stem and progenitor cells from which they are derived, undergo epigenetic and metabolic reprogramming allowing them to respond more effectively to antigen exposures unrelated to the original stimulus. However, other processes such as granulopoiesis and cross-reactive adaptive immunity may also play a role. Heterologous immunity and NSEs may be influenced by several endogenous and exogenous variables.
We discuss the quality of available data, the importance of understanding mechanisms of heterologous protection, and its implications for vaccination strategies.
https://www.crd.york.ac.uk/PROSPERO/view/CRD42023400375, identifier CRD42023400375.
Journal Article
Tuberculosis in patients with systemic lupus erythematosus
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis ( M. tb ), with approximately 10 million new cases reported worldwide annually. Patients with immunocompromised states or those receiving immunosuppressive therapy for autoimmune diseases are at higher risk of M. tb infection or reactivation. The chronic autoimmune disease, systemic lupus erythematosus (SLE), is associated with a higher risk of M. tb infection and TB disease during conventional treatment with corticosteroids and immunosuppressants. However, whether risk of TB is influenced by the immune disturbances associated with active SLE when patients are not receiving immunosuppressant treatment remains unclear. In this review, we describe the pathogenesis of TB and SLE and consider how autoimmune responses in SLE could influence TB risk.
Journal Article
Development and application of the direct mycobacterial growth inhibition assay: a systematic review
First described by Wallis et al. in 2001 for the assessment of TB drugs, the direct mycobacterial growth inhibition assay (MGIA) offers a tractable
tool measuring the combined influences of host immunity, strain virulence and intervention effects. Over the past 13 years, we have led efforts to adapt the direct MGIA for the assessment of TB vaccines including optimisation, harmonisation and validation of BCG vaccine-induced responses as a benchmark, as well as assay transfer to institutes worldwide.
We have performed a systematic review on the primary published literature describing the development and applications of the direct MGIA from 2001 to June 2023 in accordance with the PRISMA reporting guidelines.
We describe 63 studies in which the direct MGIA has been applied across species for the evaluation of TB drugs and novel TB vaccine candidates, the study of clinical cohorts including those with comorbidities, and to further understanding of potential immune correlates of protection from TB. We provide a comprehensive update on progress of the assay since its conception and critically evaluate current findings and evidence supporting its utility, highlighting priorities for future directions.
While further standardisation and validation work is required, significant advancements have been made in the past two decades. The direct MGIA provides a potentially valuable tool for the early evaluation of TB drug and vaccine candidates, clinical cohorts, and immune mechanisms of mycobacterial control.
https://www.crd.york.ac.uk/prospero/, identifier CRD42023423491.
Journal Article
MMR Vaccine Attitude and Uptake Research in the United Kingdom: A Critical Review
This review critically assesses the body of research about Measles-Mumps-and-Rubella (MMR) vaccine attitudes and uptake in the United Kingdom (UK) over the past 10 years. We searched PubMed and Scopus, with terms aimed at capturing relevant literature on attitudes about, and uptake of, the MMR vaccine. Two researchers screened for abstract eligibility and after de-duplication 934 studies were selected. After screening, 40 references were included for full-text review and thematic synthesis by three researchers. We were interested in the methodologies employed and grouped findings by whether studies concerned: (1) Uptake and Demographics; (2) Beliefs and Attitudes; (3) Healthcare Worker Focus; (4) Experimental and Psychometric Intervention; and (5) Mixed Methods. We identified group and individual level determinants for attitudes, operating directly and indirectly, which influence vaccine uptake. We found that access issues, often ignored within the public “anti-vax” debate, remain highly pertinent. Finally, a consistent theme was the effect of misinformation or lack of knowledge and trust in healthcare, often stemming from the Wakefield controversy. Future immunisation campaigns for children, including for COVID-19, should consider both access and attitudinal aspects of vaccination, and incorporate a range of methodologies to assess progress, taking into account socio-economic variables and the needs of disadvantaged groups.
Journal Article
Inflammation and immune activation are associated with risk of Mycobacterium tuberculosis infection in BCG-vaccinated infants
Tuberculosis vaccine development is hindered by the lack of validated immune correlates of protection. Exploring immune correlates of risk of disease and/or infection in prospective samples can inform this field. We investigate whether previously identified immune correlates of risk of TB disease also associate with increased risk of
M.tb
infection in BCG-vaccinated South African infants, who became infected with
M.tb
during 2-3 years of follow-up.
M.tb
infection is defined by conversion to positive reactivity in the QuantiFERON test. We demonstrate that inflammation and immune activation are associated with risk of
M.tb
infection. Ag85A-specific IgG is elevated in infants that were subsequently infected with
M.tb
, and this is coupled with upregulated gene expression of immunoglobulin-associated genes and type-I interferon. Plasma levels of IFN-
α
2, TNF-
α
, CXCL10 (IP-10) and complement C2 are also higher in infants that were subsequently infected with
M.tb
.
The identification of immune correlates of protection in humans would inform on the design and development of tuberculosis vaccine candidates. In this work, authors examine samples collected from South African infants, to determine whether the correlates of risk of tuberculosis disease, previously identified in this population, are also correlates of risk of M. tuberculosis infection.
Journal Article
The Chorioallantoic Membrane Assay in Nanotoxicological Research—An Alternative for In Vivo Experimentation
Nanomaterials unveil many applicational possibilities for technical and medical purposes, which range from imaging techniques to the use as drug carriers. Prior to any human application, analysis of undesired effects and characterization of their toxicological profile is mandatory. To address this topic, animal models, and rodent models in particular, are most frequently used. However, as the reproducibility and transferability to the human organism of animal experimental data is increasingly questioned and the awareness of animal welfare in society increases at the same time, methodological alternatives are urgently required. The chorioallantoic membrane (CAM) assay is an increasingly popular in ovo experimental organism suitable for replacement of rodent experimentation. In this review, we outline several application fields for the CAM assay in the field of nanotoxicology. Furthermore, analytical methods applicable with this model were evaluated in detail. We further discuss ethical, financial, and bureaucratic aspects and benchmark the assay with other established in vivo models such as rodents.
Journal Article
Early mucosal responses following a randomised controlled human inhaled infection with attenuated Mycobacterium bovis BCG
The development of an effective vaccine against
Mycobacterium tuberculosis
is hampered by an incomplete understanding of immunoprotective mechanisms. We utilise an aerosol human challenge model using attenuated
Mycobacterium bovis
BCG, in BCG-naïve UK adults. The primary endpoint of this study (NCT03912207) was to characterise the early immune responses induced by aerosol BCG infection, the secondary endpoint was to identify immune markers associated with in-vitro protection. Blinded volunteers were randomised to inhale 1 × 10
7
CFU aerosolised BCG or 0.9% saline (20:6); and sequentially allocated to bronchoscopy at day 2 or 7 post-inhalation (10 BCG, 3 saline each timepoint). In the bronchoalveolar lavage post-aerosol BCG infection, there was an increase in frequency of eosinophils, neutrophils, NK cells and Donor-Unrestricted T cells at day 7, and the frequency of antigen presenting cells decreased at day 7 compared with day 2. The frequency of interferon-gamma+ BCG-specific CD4+ T cells increased in the BAL and peaked in the blood at day 7 post-BCG infection compared to day 2. BAL cells at day 2 and day 7 upregulated gene pathways related to phagocytosis, MHC-II antigen loading, T cell activation and proliferation. BCG’s lack of key virulence factors and its failure to induce granulomas, may mean the observed immune responses do not fully recapitulate
Mycobacterium tuberculosis
infection. However, human infection models can provide unique insights into early immune mechanisms, informing vaccine design for complex pathogens.
In this study, Marshall et al. studied early immune responses in the lung and blood after an aerosol infection with BCG. Understanding which cells respond to this infection can help us understand how to design new tuberculosis vaccines.
Journal Article
Chronovaccination: Harnessing circadian rhythms to optimize immunisation strategies
Vaccination, as a public health measure, offers effective protection of populations against infectious diseases. Optimising vaccination efficacy, particularly for higher-risk individuals, like the elderly whose immunocompromised state can prevent the development of robust vaccine responses, is vital. It is now clear that 24-hour circadian rhythms, which govern virtually all aspects of physiology, can generate oscillations in immunological responses. Consequently, vaccine efficacy may depend critically on the time of day of administration(s), including for Covid-19, current vaccines, and any future diseases or pandemics. Published clinical vaccine trials exploring diurnal immune variations suggest this approach could represent a powerful adjunct strategy for optimising immunisation, but important questions remain to be addressed. This review explores the latest insights into diurnal immune variation and the outcomes of circadian timing of vaccination or ‘chronovaccination’.
Journal Article