Characterization of B-cell Responses to Zika Virus (ZIKV)

Objective: Most ZIKV infections occur in regions endemic for the related dengue virus (DENV). Anti-DENV antibodies have been demonstrated to cross-react with ZIKV. Some neutralize ZIKV infection while others mediate antibody-dependent enhancement (ADE), exacerbating ZIKV infection and complicating diagnosis of the etiologic agent. We aimed to characterize the humoral immune response in a ZIKV+, DENV- experienced individual in order to explore this anamnestic response and identify antibodies that may be useful in the development of therapeutic agents. Design and Methodology: Peripheral blood mononuclear cells (PBMCs) were collected from an individual (TT66) who was newly infected with ZIKV but had two previous DENV infections. Plasmablasts were isolated and analyses conducted using Atreca's Immune Repertoire CaptureTM technology. Monoclonal antibodies (mAbs) derived from TT66 during their acute and convalescent phase of ZIKV infection were screened in vitro for ZIKV and DENV binding and neutralization activity. Epitopes were then mapped using a shotgun mutagenesis approach. Results: We observed clonal expansion of two distinct antibody lineages representing 70% of total immunoglobulin sequences from TT66. We screened 18 mAbs representing two major lineages and five smaller families for neutralization and ADE between DENV and ZIKV. No highly typespecific mAbs were observed but rather a diverse pattern of neutralization, even within an individual lineage. Shotgun mutagenesis epitope mapping demonstrated epitopes for two of these broadly neutralizing mAb lineages lay within domain II ofE, close to the fusion loop. Conclusions: Results suggest that neutralizing antibody responses to ZIKV are extensively shaped by previous DENV exposure.

Immunological abnormalities in HTLV-1 infected Jamaican children (abstract)

This paper reports on the immunological findings of a case control study of 50 infective dermatitis (ID) patients and 36 atopic eczema (AE) patients undertaken between December 1990 and August 1991. It also reports on a comparison of these results with those of age and sex matched normal controls, and age and sex matched HTLV-I infected asymptomatic children. Investigations of their immune systems showed that both ID and AE patients had normal responses to delayed hypersensitivity skin tests, and normal compliment levels. However there was a marked increase in the activity of both T and B lymphocyte systems, with all immunoglobulin levels being significantly increased in ID patients versus others. The CD4:CD8 ratio was increased, with an increase in the CD4 counts. Monoclonal antibody tests showed increased T cell activation. The results confirm immune dysfunction though the precise mechanism of the immunodysregulation remains to be determined. (AU)

Respiratory allergy

Asthma is the most common chronic disease of childhood in North America. In recent years there has been an increase in the number of asthma deaths, this increase in mortality is occurring despite advances in understanding and medical management. In diagnosing allergy, the history is all important. Precipitating factors is the single most helpful item in separating allergic from non-allergic rhinitis and asthma. Antigens such as pollen, animal danders, insect-derived dust and mould spores are the main offenders. Two approaches have been adopted in the prevention and treatment. One is the avoidance of antigens in early infancy, to prevent the allergic state from developing. The second is antigen avoidance after the allergic state has developed, in order to reduce the symptoms

Mononuclear cells in sickle cell disease: subpopulations and in vitro response to mitogens

The subpopulations of mononuclear cells and the lymphocyte proliferative capacity following mitogen stimulation were studied in 22 patients with homozygous sickle cell (SS) disease and 25 controls with a normal haemoglobin (AA) genotype. The total number of lymphocytes in peripheral blood samples was higher in SS patients compared to controls. Expressed as a percentage of total lymphocytes, the number of B lymphocytes (detected by membrane immunoglobulin Fluorescence) was normal and of T lymphocytes (identified by sheep erythocyte rosetting) was slightly reduced in SS disease. Expressed in absolute numbers, both B and T lymphoctes were increased. Lymphocyte proliferation measured by tritium labelled thymidine incorporation following stimulation with phytohaemaeglutin A and concanavalin A was normal. Following pokeweed mitogen stimulation, thymidine incorporation was significantly increased in SS disease although normal when expressed as a stimualtion index. These results do not suggest a major defect in cell mediated immunity in sickle cell disease. The number of circulating monocytes was increased in SS disease and correlated inversely with the number of reticulocyytes (r= -0.58, p < 0.005) (AU)