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

Astroglial phenotypes in traumatic brain injury and their relationship with neuronal degeneration

Astrocytes are key players in the Central Nervous System injury.By not completely defined pathways, reactive astrocytes may suffer a pathological remodeling engaging a pro-inflammatory phenotype that is very stable and promote further neuroinflammation andneurodegeneration. We here aimed to define the spatio-temporaldistribution of astroglial phenotypes after traumatic brain injury andthe consequences for neuronal survival and behavioral parameters.Following a stereotaxic stab wound injury (0.8 mm needle, coordinates 2 mm posterior and lateral to Bregma; 1 mm depth) performedin C57BL/6 mice and immunohistochemistry on brain sections, weclassified GFAP reactive astrocytes in five different phenotypes defined using Sholl analysis (Auzmendi et al., Molec. Neurobiol. 2019).While at 1 day post-injury (DPI) GFAP+ astrocytes were not differentfrom contralateral non-injured hemisphere, at 3DPI and 7DPI highly reactive phenotypes colocalized with altered neurons in lesionpenumbra. At 14DPI highly reactive astrocytes and altered neuronswere abundant only in the lesion core. Pro-inflammatory gain offunction paradigm was achieved by administering LPS (5 mg/Kg i.p)in lesioned animals, and that resulted in a greater number of complex reactive astrocytes at 7DPI (p<0.05) and a population of C3+astrocytes. On the other hand, loss of function paradigm with chemical NFkB blocker sulfasalazine (150 mg/kg i.p) significantly reducedhighly reactive astrocytes (p<0.05) and showed reduced neuronaldeath. Animal motor deficits were analyzed by computer-assistedopen field, but at 7DPI we were unable to detect significative differences among groups probably due to the small lesion size. Weconclude that increased GFAP+ higher complexity astrocytes areassociated with increased neuronal death and that NFkB pathway islikely to be involved in the pathological conversion to the pro-inflammatory-neurodegenerative phenotype.Fil: Cieri, M. B.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Mailing, Ingrid Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Villarreal, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ramos, Alberto Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaLXV Reunión anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Asociación Argentina de FisiologíaArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de Fisiologí

A mycobacterial growth inhibition assay (MGIA) for bovine TB vaccine development

Human tuberculosis remains a significant cause of mortality and morbidity throughout the world. The global economic impact of bovine TB is considerable. An effective vaccine would be the most cost-effective way to control both epidemics, particularly in emerging economies. TB vaccine research would benefit from the identification of an immune correlate of protection with which vaccines could be gated at both preclinical and clinical levels. In-vitro mycobacterial growth inhibition assays (MGIA) are functional assays that include most aspects of the complex host immune response to mycobacteria, and they may serve as functional immune correlates for vaccine development. We applied to cattle an MGIA that was developed for use with human and murine samples. Several technical difficulties were encountered while transferring it to the cattle model. However, our data demonstrate that the assay was not discriminatory in cattle and further work is needed before using it for bovine TB vaccine development

First records of the iceryine scale insects \u3ci\u3eCrypticerya brasiliensis\u3c/i\u3e (Hempel) and \u3ci\u3eCrypticerya genistae\u3c/i\u3e (Hempel) (Hemiptera: Monophlebidae) for Colombia

Abstract. Crypticerya brasiliensis (Hempel) and Crypticerya genistae (Hempel) (Hemiptera: Monophlebidae: Iceryini) are herein reported for the fi rst time in Colombia. The above two species and Crypticerya multicicatrices Kondo and Unruh and Crypticerya zeteki (Cockerell) are briefl y diagnosed based on the adult females. The presence of C. zeteki in Colombia is confi rmed and a key to the adult females of species of the tribe Iceryini reported in Colombia is provided. Resumen. Se reportan por primera vez a Crypticerya brasiliensis (Hempel) y Crypticerya genistae (Hempel) (Hemiptera: Monophlebidae: Iceryini) en Colombia. Las dos especies arriba mencionadas junto con Crypticerya multicicatrices Kondo y Unruh y Crypticerya zeteki (Cockerell) se diagnostican brevemente con base en morfología de las hembras adultas. Se confi rma la presencia de C. zeteki en Colombia y se provee una clave para las hembras adultas de las especies de la tribu Iceryini registradas en Colombia

A multi-antigenic adenoviral-vectored vaccine improves BCG-induced protection of goats against pulmonary tuberculosis infection and prevents disease progression

The “One world, one health” initiative emphasizes the need for new strategies to control human and animal tuberculosis (TB) based on their shared interface. A good example would be the development of novel universal vaccines against Mycobacterium tuberculosis complex (MTBC) infection. This study uses the goat model, a natural TB host, to assess the protective effectiveness of a new vaccine candidate in combination with Bacillus Calmette-Guerin (BCG) vaccine. Thirty-three goat kids were divided in three groups: Group 1) vaccinated with BCG (week 0), Group 2) vaccinated with BCG and boosted 8 weeks later with a recombinant adenovirus expressing the MTBC antigens Ag85A, TB10.4, TB9.8 and Acr2 (AdTBF), and Group 3) unvaccinated controls. Later on, an endobronchial challenge with a low dose of M. caprae was performed (week 15). After necropsy (week 28), the pulmonary gross pathology was quantified using high resolution Computed Tomography. Small granulomatous pulmonary lesions (< 0.5 cm diameter) were also evaluated through a comprehensive qualitative histopathological analysis. M. caprae CFU were counted from pulmonary lymph nodes. The AdTBF improved the effects of BCG reducing gross lesion volume and bacterial load, as well as increasing weight gain. The number of Ag85A-specific gamma interferon-producing memory T-cells was identified as a predictor of vaccine efficacy. Specific cellular and humoral responses were measured throughout the 13-week post-challenge period, and correlated with the severity of lesions. Unvaccinated goats exhibited the typical pathological features of active TB in humans and domestic ruminants, while vaccinated goats showed only very small lesions. The data presented in this study indicate that multi-antigenic adenoviral vectored vaccines boosts protection conferred by vaccination with BCG

Defining the Genes Required for Survival of Mycobacterium bovis in the Bovine Host Offers Novel Insights into the Genetic Basis of Survival of Pathogenic Mycobacteria

Supplementary dataset from "Defining the genes required for survival of Mycobacterium bovis in the bovine host offers novel insights into the genetic basis of survival of pathogenic mycobacteria

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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