Project description:To study the plasmablast response to influenza vaccines We want to test and see that LAIV, TIV and ID TIV induced different plasmablast response We take peripheral plasmablast and test its response to influenza vaccines at day 7 after vaccination. This array data set is for day 0 (before vaccines)
Project description:The normal response to influenza A infection is to remain asymptomatic; indeed, a study of volunteers who tested positive for antibodies against 2009 H1N1 revealed that a majority did not experience symptoms. However, studies of influenza pandemics since the 20th century, and to a lesser degree seasonal flu, suggest that pregnancy increases influenza-associated morbidity and mortality. The confounding effect of pregnancy has been well established to adversely alter the clinical course of influenza, with short term complications to mother and baby apparent, and long-term consequences to the fetus hypothesized. However, how the condition of pregnancy impacts long-term maternal anti-influenza immunity remains contentious; while vaccination studies suggest humoral responses sufficient for protection, published research on adaptive immune responses against influenza formed during pregnancy is limited. This study expands upon published work from our lab and others by comprehensively examining compartmental and systemic changes following pandemic A/California/07/2009 influenza infection. Previously, we linked seasonal influenza infection to clinical observations of adverse outcomes in pregnancy, enhanced lung and placental histopathology, and reduced control of viral replication in lungs of infected pregnant mothers. Here, we observe that the results of a lower infectious dose of pandemic influenza are similar to that of seasonal influenza. Importantly, we expand upon work which suggests infection during pregnancy may also affect humoral immunity. Our observations of reduced early antibody hemagglutinin inhibition and virus neutralization which resolved within 8 weeks of delivery demonstrate that influenza infection impacts antibody maturation mechanisms without alterations to B cell frequency or antibody secretion. This hypothesis is further supported by plasmablast transcriptional data, which demonstrates downregulated B cell metabolism and post-translational modification systems only among pregnant animals. These findings corroborate a link between adverse pregnancy outcomes and severe pathology observed during influenza infection, and propose resolving humoral deficiencies following influenza infection confounded by pregnancy. Additional studies are required to specify the involvement of plasmablast metabolism with early humoral immunity abnormalities to best guide vaccination strategies and improve our understanding of the immunological consequences of pregnancy.
Project description:Seasonal influenza is a primary public health burden in the USA and globally. Annual vaccination programs are designed on the basis of circulating influenza viral strains. However, the effectiveness of the seasonal influenza vaccine is highly variable between seasons and among individuals. A number of factors are known to influence vaccination effectiveness including age, sex, and comorbidities. Here, we sought to determine whether whole blood gene expression profiling prior to vaccination is informative about pre-existing immunological status and the immunological response to vaccine. We performed whole transcriptome analysis using RNA sequencing (RNAseq) of whole blood samples obtained prior to vaccination from participants enrolled in an annual influenza vaccine trial. Serological status prior to vaccination and 28 days following vaccination were assessed using the hemagglutination inhibition assay (HAI) to define baseline immune status and the response to vaccination. We find evidence that genes with immunological functions are increased in expression in individuals with higher pre-existing immunity and in those individuals who mount a greater response to vaccination. Using a random forest model we find that this set of genes can be used to predict vaccine response with a performance similar to a model that incorporates physiological and prior vaccination status alone. Our study shows that increased expression of immunological genes, possibly reflecting greater plasmablast cell populations, prior to vaccination is associated with an enhanced response to vaccine. Furthermore, in the absence of demographic and physiological information gene expression signatures are informative about the likely response of an individual to seasonal influenza vaccination.
Project description:<p>We developed an improved high throughput sequencing approach to measure the quantities and sequences of the repertoire of antibody heavy chain RNA in a blood sample. Using this approach we analyzed the antibody repertoire in response to yearly vaccinations with influenza vaccines TIV and LAIV in healthy adults in two subsequent years. We determined vaccine response patterns specific to LAIV and TIV and found antibody sequences that were shared between two samples of the same individuals following influenza vaccination in subsequent years, thereby providing a genetic measurement of B-cell memory recall.</p>
Project description:To study the plasmablast response to influenza vaccines We want to test and see that LAIV, TIV and ID TIV induced different plasmablast response
Project description:To study the plasmablast response to influenza vaccines We want to test and see that LAIV, TIV and ID TIV induced different plasmablast response
Project description:To investigate the nasal transcriptional response and peripheral plasmablast response in acute influenza infection 1. To investigate the nasal transcriptional response with real time PCR. 2. To measure plasmablast response by PPAb analysis.