Measles virus-specific murine T cell clones: characterization of fine specificity function.

Measles virus (MV)-specific murine helper T cell clones (Thy-1.2+, CD4+, CD8-) were generated from mice immunized with MV-infected mouse brain homogenate by limiting dilution and in vitro stimulation of spleen cells with UV-inactivated MV Ag. The protein specificity of 7 out of 37 stable T cell clones, which displayed MHC-restricted MV Ag recognition, could be assessed by using purified MV proteins. Two fusion (F) protein-specific, two hemagglutinin-specific, and three nucleoprotein- or matrix protein-specific clones were shown to be established. The F protein-specific T cell clones together with a pane

Host resistance to rat cytomegalovirus (RCMV) and immune function in adult PVG rats fed herring from the contaminated Baltic Sea

The immunotoxic potential of many classes of environmental contaminants has been well established in laboratory studies, with much attention being focussed on aryl hydrocarbon (Ah)-receptor binding polychlorinated biphenyl (PCB), polychlorinated dibenzo-p-dioxin (PCDD), and polychlorinated dibenzofuran (PCDF) congeners. In a semi-field study, we previously showed that harbour seals (Phoca vitulina) fed herring from the contaminated Baltic Sea had lower natural killer cell activity, T-lymphocyte functionality and delayed-type hypersensitivity responses than seals fed herring from the relatively uncontaminated Atlantic Ocean. While ethical and practical constraints preclude in-depth studies in seals, specific reagents and a wider array of immune function tests allow such studies in laboratory rats. We therefore carried out a feeding study in rats aimed at extending our observations of contaminant-induced immunosuppression in harbour seals. The same two herring batches used in the seal study were freeze-dried, supplemented and fed. to female adult PVG rats for a period of 4 1/4 months. Daily contaminant intakes of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalents (TEQ) were estimated to be 0.3 ng/kg body weight and 1.6 ng/kg in the Atlantic and Baltic groups, respectively. At the end of the feeding experiment, no contaminant-related changes in spleen CD4+/CD8+cellularity, natural killer cell activity, or mitogen-induced proliferative responses of thymus or spleen cells could be detected. However, total thymocyte numbers and thymus CD4+/CD8+ratios were reduced in the Baltic group. A novel model was established to assess the specific T-cell response to rat cytomegalovirus (RCMV). When applied to the feeding study, no differences between the Atlantic and Baltic groups in the RCMV-induced proliferative T-lymphocyte responses could be detected, but virus titres in salivary glands of infected rats of the Baltic Sea group were higher. These elevated RCMV titres and changes in thymus cellularity suggest that the dietary exposure to low levels of contaminants may have been immunotoxic at a level which our immune function test could not otherwise detect. While the herring diet per se appeared to have an effect on several immune function parameters, lower plasma thyroid hormone levels in the Baltic Sea group of rats confirmed that exposure to the environmental mixture of contaminants led to adverse PHAH-related health effects

Dynamics of the serologic response in vaccinated and unvaccinated mumps cases during an epidemic

In the last decade, several mumps outbreaks were reported in various countries despite high vaccination coverage. In most cases,

Epidemic of mumps among vaccinated persons, the Netherlands, 2009-2012

To analyze the epidemiology of a nationwide mumps epidemic in the Netherlands, we reviewed 1,557 notified mumps cases in persons who had disease onset during September 1, 2009-August 31, 2012. Seasonality peaked in sprin

Comparison of norovirus genogroup I, II and IV seroprevalence among children in the Netherlands, 1963, 1983 and 2006

Noroviruses are a major cause of acute gastroenteritis worldwide and are a genetically diverse group of viruses. Since 2002, an increasing number of norovirus outbreaks have been reported globally, but it is not clear whether this increase has been caused by a higher awareness or reflects the emergence of new genogroup II genotype 4 (GII.4) variants. The hypothesis that norovirus prevalence has increased post-2002 and is related to the emergence of GII.4 is tested in this study. Sera collected from children aged <5 years of three Dutch cross-sectional population based cohorts in 1963, 1983 and 2006/2007 (n=143, n=130 and n=376, respectively) were tested for specific serum IgG by protein array using antigens to GII.4 and a range of other antigens representing norovirus GI, GII and GIV genotypes. The protein array was validated by paired sera of norovirus infected patients and supernatants of B-cell cultures with single epitope specificity. Evidence for norovirus infection was found to be common among Dutch children in each cohort, but the prevalence towards different genotypes changed over time. At the genogroup level, GI seroprevalence decreased significantly between 1963 and 2006/2007, while a significant increase of GII and, in particular, specific antibodies of the genotype GII.4 was detected in the 2006/2007 cohort. There were no children with only GII.4 antibodies in the 1963 cohort. This study shows that the high GII.4 norovirus incidence in very young children is a recent phenomenon. These findings are of importance for vaccine development and trials that are currently focusing mostly on GII.4 viruses

Additional evidence on serological correlates of protection against measles: An observational cohort study among once vaccinated children exposed to measles

To assess correlates of protection against measles and against subclinical measles virus (MV) infection, we recruited once-vaccinated children from geographic regions associated with increased MV circulation and/or at schools with low vaccination coverage in the Netherlands. Paired blood samples were collected shortly after onset of the measles outbreak and after the outbreak. A questionnaire was used to document the likelihood of exposure to MV and occurrence of measles-like symptoms. All blood samples were tested for MV-specific antibodies with five different assays. Correlates of protection were assessed by considering the lowest neutralizing antibody levels in children without MV infection, and by ROC analyses. Among 91 participants, two seronegative children (2%) developed measles, and an additional 19 (23%) experienced subclinical MV infection. The correlate of protection against measles was lower than 0.345 IU/mL. We observed a decreasing attack rate of subclinical MV infection with increasing levels of specific antibodies until 2.1 IU/mL, above which no subclinical MV infections were detected. The ROC analyses found a correlate of protection of 1.71 IU/mL (95% CI 1.01–2.11) for subclinical MV infection. Our correlates of protection were consistent with previous estimates. This information supports the analyses of serosurveys to detect immunity gaps that require targeted intervention strategies

An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment

The world is entering a new era of the COVID-19 pandemic in which there is an increasing call for reliable antibody testing. To support decision making on the deployment of serology for either population screening or diagnostics, we present a detailed comparison of serological COVID-19 assays. We show that among the selected assays there is a wide diversity in assay performance in different scenarios and when correlated to virus neutralizing antibodies. The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, has the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies. The large variety of available serological assays requires proper assay validation before deciding on deployment of assays for specific applications

Mumps virus pathogenesis: Insights and knowledge gaps

The recent mumps outbreaks among MMR vaccinated persons have raised questions about the biological mechanisms related to mumps symptoms and complications in the background of waning immunity. Contrary to other paramyxoviruses, the understanding of mumps virus pathogenesis is limited, and further in-depth clinical studies are required to provide answers to important research questions

Viral replication and development of specific immunity in macaques after infection with different measles virus strains.

Cynomolgus monkeys (Macaca fascicularis) were experimentally infected with a wild type measles virus (MV) strain (MV-BIL). Following intratracheal inoculation with different infectious doses, the virus could be isolated from peripheral blood mononuclear cells (PBMC), lung lavage cells, and pharyngeal cells. The kinetics of the cell-associated viremia was similar in all infected animals. They developed specific serum IgM, IgG, and neutralizing antibody responses as well as MV-specific T cell-mediated immunity. Monkeys infected intratracheally or intramuscularly with the wild type MV-Edmonston or the attenuated MV-Schwartz strain showed a lower level of PBMC-associated viremia and less pronounced specific IgM responses. Nine months after infection with MV strains, all of the monkeys were protected from intratracheal reinfection with MV-BIL. This monkey model is suitable for study of new generations of vaccines and vaccination strategies for measles