Dataset Information

Measles immune suppression: lessons from the macaque model.

ABSTRACT: Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV) infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulent in non-human primates. By performing a comprehensive study of virological, immunological, hematological and histopathological observations made in animals euthanized at different time points after MV infection, we developed a model explaining measles immune suppression which fits with the "measles paradox". Here we show that MV preferentially infects CD45RA(-) memory T-lymphocytes and follicular B-lymphocytes, resulting in high infection levels in these populations. After the peak of viremia MV-infected lymphocytes were cleared within days, followed by immune activation and lymph node enlargement. During this period tuberculin-specific T-lymphocyte responses disappeared, whilst strong MV-specific T-lymphocyte responses emerged. Histopathological analysis of lymphoid tissues showed lymphocyte depletion in the B- and T-cell areas in the absence of apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell follicles and reappearance of proliferating cells. Our findings indicate an immune-mediated clearance of MV-infected CD45RA(-) memory T-lymphocytes and follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this depletion, explaining the short duration of measles lymphopenia yet long duration of immune suppression.

SUBMITTER: de Vries RD

PROVIDER: S-EPMC3431343 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Measles immune suppression: lessons from the macaque model.

de Vries Rory D RD McQuaid Stephen S van Amerongen Geert G Yüksel Selma S Verburgh R Joyce RJ Osterhaus Albert D M E AD Duprex W Paul WP de Swart Rik L RL

PLoS pathogens 20120830 8

Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV) infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulen ...[more]

PMID: 22952446

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Project description:BACKGROUND: The Lives Saved Tool (LiST) has been developed to estimate the impact of health interventions and can consider multiple interventions simultaneously. Given its increasing usage by donor organizations and national program planner, we compare the LiST measles model to the widely used World Health Organization's Department of Immunization, Vaccines and Biologicals (WHO/IVB) measles model which is used to produce estimates serving as a major indicator of monitoring country measles epidemics and the progress of measles control. METHODS: We analyzed the WHO/IVB models and the LiST measles model and identified components and assumptions held in each model. We contrasted the important components, and compared results from the two models by applying historical measles containing vaccine (MCV) coverages and the default values of all parameters set in the models. We also conducted analyses following a hypothetical scenario to understand how both models performed when the proportion of population protected by MCV declined to zero percent in short time period. RESULTS: The WHO/IVB measles model and the LiST measles model structures differ: the former is a mixed model which applies surveillance data adjusted for reporting completeness for countries with good disease surveillance system and applies a natural history model for countries with poorer disease control program and surveillance system, and the latter is a cohort model incorporating country-specific cause-of-death (CoD) profiles among children under-five. The trends of estimates of the two models are similar, but the estimates of the first year are different in most of the countries included in the analysis. The two models are comparable if we adjust the measles CoD in the LiST to produce the same baseline estimates. In addition, we used the models to estimate the potential impact of stopping using measles vaccine over a 7-year period. The WHO/IVB model produced similar estimates to the LiST model with adjusted CoD. But the LiST model produced low estimates for countries with very low or eliminated measles infection that may be inappropriate. CONCLUSIONS: The study presents methodological and quantitative comparisons between the WHO/IVB and the LiST measles models that highlights differences in model structures and may help users to better interpret and contrast estimates of the measles death from the two models. The major differences are resulted from the usage of case-fatality rate (CFR) in the WHO/IVB model and the CoD profile in the LiST. Both models have their own advantages and limitations. Users should be aware of the issue and apply as update country parameters as possible. Advanced models are expected to validate the policy-planning tools in the future.

Dataset Information

Measles immune suppression: lessons from the macaque model.

Publications

Measles immune suppression: lessons from the macaque model.

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