Profiling of Humoral Response to Influenza A(H1N1)pdm09 Infection and Vaccination Measured by a Protein Microarray in Persons with and without History of Seasonal Vaccination

Background

The influence of prior seasonal influenza vaccination on the antibody response produced by natural infection or vaccination is not well understood.

Methods

We compared the profiles of antibody responses of 32 naturally infected subjects and 98 subjects vaccinated with a 2009 influenza A(H1N1) monovalent MF59-adjuvanted vaccine (Focetria®, Novartis), with and without a history of seasonal influenza vaccination. Antibodies were measured by hemagglutination inhibition (HI) assay for influenza A(H1N1)pdm09 and by protein microarray (PA) using the HA1 subunit for seven recent and historic H1, H2 and H3 influenza viruses, and three avian influenza viruses. Serum samples for the infection group were taken at the moment of collection of the diagnostic sample, 10 days and 30 days after onset of influenza symptoms. For the vaccination group, samples were drawn at baseline, 3 weeks after the first vaccination and 5 weeks after the second vaccination.

Results

We showed that subjects with a history of seasonal vaccination generally exhibited higher baseline titers for the various HA1 antigens than subjects without a seasonal vaccination history. Infection and pandemic influenza vaccination responses in persons with a history of seasonal vaccination were skewed towards historic antigens.

Conclusions

Seasonal vaccination is of significant influence on the antibody response to subsequent infection and vaccination, and further research is needed to understand the effect of annual vaccination on protective immunity.     

Effects of Dementia-Care Mapping on Residents and Staff of Care Homes: A Pragmatic Cluster-Randomised Controlled Trial

Background

The effectiveness of dementia-care mapping (DCM) for institutionalised people with dementia has been demonstrated in an explanatory cluster-randomised controlled trial (cRCT) with two DCM researchers carrying out the DCM intervention. In order to be able to inform daily practice, we studied DCM effectiveness in a pragmatic cRCT involving a wide range of care homes with trained nursing staff carrying out the intervention.

Methods

Dementia special care units were randomly assigned to DCM or usual care. Nurses from the intervention care homes received DCM training and conducted the 4-months DCM-intervention twice during the study. The primary outcome was agitation, measured with the Cohen-Mansfield agitation inventory (CMAI). The secondary outcomes included residents’ neuropsychiatric symptoms (NPSs) and quality of life, and staff stress and job satisfaction. The nursing staff made all measurements at baseline and two follow-ups at 4-month intervals. We used linear mixed-effect models to test treatment and time effects.

Results

34 units from 11 care homes, including 434 residents and 382 nursing staff members, were randomly assigned. Ten nurses from the intervention units completed the basic and advanced DCM training. Intention-to-treat analysis showed no statistically significant effect on the CMAI (mean difference between groups 2·4, 95% CI −2·7 to 7·6; p = 0·34). More NPSs were reported in the intervention group than in usual care (p = 0·02). Intervention staff reported fewer negative and more positive emotional reactions during work (p = 0·02). There were no other significant effects.

Conclusions

Our pragmatic findings did not confirm the effect on the primary outcome of agitation in the explanatory study. Perhaps the variability of the extent of implementation of DCM may explain the lack of effect.

Trial Registration

Dutch Trials Registry NTR2314.     

Comparative analysis of avian influenza virus diversity in poultry and humans during a highly pathogenic avian influenza A (H7N7) virus outbreak

Although increasing data have become available that link human adaptation with specific molecular changes in nonhuman influenza viruses, the molecular changes of these viruses during a large highly pathogenic avian influenza virus (HPAI) outbreak in poultry along with avian-to-human transmission have never been documented. By comprehensive virologic analysis of combined veterinary and human samples obtained during a large HPAI A (H7N7) outbreak in the Netherlands in 2003, we mapped the acquisition of human adaptation markers to identify the public health risk associated with an HPAI outbreak in poultry. Full-length hemagglutinin (HA), neuraminidase (NA), and PB2 sequencing of A (H7N7) viruses obtained from 45 human cases showed amino acid variations at different codons in HA (n=20), NA (n=23), and PB2 (n=23). Identification of the avian sources of human virus infections based on 232 farm sequences demonstrated that for each gene about 50% of the variation was already present in poultry. Polygenic accumulation and farm-to-farm spread of known virulence and human adaptation markers in A (H7N7) virus-infected poultry occurred prior to farm-to-human transmission. These include the independent emergence of HA A143T mutants, accumulation of four NA mutations, and farm-to-farm spread of virus variants harboring mammalian host determinants D701N and S714I in PB2. This implies that HPAI viruses with pandemic potential can emerge directly from poultry. Since the public health risk of an avian influenza virus outbreak in poultry can rapidly change, we recommend virologic monitoring for human adaptation markers among poultry as well as among humans during the course of an outbreak in poultry.     

The use of Bartonella henselae-specific age dependent IgG and IgM in diagnostic models to discriminate diseased from non-diseased in Cat Scratch Disease serology

Cat Scratch Disease (CSD) is caused by Bartonella henselae infection and is a common cause of regional lymphadenopathy. The diagnosis of CSD largely depends on serology, but is hampered by both low sensitivity and specificity of the applied IgG and IgM assays. Using an in-house ELISA, we detected a significant age-dependent increase in the IgG levels in the general population compared to CSD patients. With this knowledge, we developed diagnostic models to differentiate diseased from non-diseased persons. Evaluation of these models using samples from PCR-positive patients (n=155) and age-matched controls (n=244) showed an important increase in the assay performance if the combination of the IgG and IgM results were taken into account. If the specificity was set at 98% the sensitivity was only 45% and 32% for the IgM and IgG ELISA, respectively but increased to 59% when these results were combined. Also the use of age-dependent factors further improved the clinical relevance of the outcome raising the sensitivity to 64%. Although the sensitivity of the ELISA remains low we conclude that the use of models using the combination of both IgM and IgG test results and age-depending factors can be a useful diagnostic tool in the serodiagnosis of CSD.     

Comparative Analyses of Data Independent Acquisition Mass Spectrometric Approaches: DIA,WiSIM‐DIA,and Untargeted DIA

Data‐independent acquisition (DIA) is an emerging technology for quantitative proteomics. Current DIA focusses on the identification and quantitation of fragment ions that are generated from multiple peptides contained in the same selection window of several to tens of m/z. An alternative approach is WiSIM‐DIA, which combines conventional DIA with wide‐SIM (wide selected‐ion monitoring) windows to partition the precursor m/z space to produce high‐quality precursor ion chromatograms. However, WiSIM‐DIA has been underexplored; it remains unclear if it is a viable alternative to DIA. We demonstrate that WiSIM‐DIA quantified more than 24 000 unique peptides over five orders of magnitude in a single 2 h analysis of a neuronal synapse‐enriched fraction, compared to 31 000 in DIA. There is a strong correlation between abundance values of peptides quantified in both the DIA and WiSIM‐DIA datasets. Interestingly, the S/N ratio of these peptides is not correlated. We further show that peptide identification directly from DIA spectra identified >2000 proteins, which included unique peptides not found in spectral libraries generated by DDA.     

Circular dichroism and structure- function relationships in cloacin DF13- immunity protein complex

Comparison of the circular dichroism (CD), of cloacin-immunity protein complex with that of cloacin and of a mutant cloacin lacking the ability to bind immunity protein, shows that the binding of immunity protein imposes a definite structure on the cloacin molecule. It is discussed that this structure probably is a prerequisite for an effective killing activity of the bacteriocin. The cloacin molecule itself probably has two domains, as was found by limited proteolysis. Comparison of the structure of two of the proteolytic fragments with that of the intact molecule by means of circular dichroism also suggests that cloacin is made up of a part without much periodic structure and of a part with more helicity. The former part being rather sensitive to proteolysis, the latter being comparatively insensitive.     

BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity

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