Vaccination Response in Individual Monozygotic Twins

Overview

Respiratory viruses are known to be risk factors for asthma (e.g respiratory syncytial viruses, RSVs, and Human Rhinoviruses, HRVs, may induce bronchiolitis, and wheezing illnesses respectively). The common flu is also known to be a risk factor and the Centers for Disease Control and Prevention (CDC) recommends that asthmatics receive the annual flu vaccine, as a high-risk group for related asthma exacerbations. The investigators will be evaluating the variation in individual responses over time after controlled immune activation following influenza vaccination of monozygotic twins, both discordant for asthma, and concordant non-asthmatic. The transition from initial healthy to immune-system activated physiological states post vaccination will provide unprecedented molecular (omics) data on the molecular dynamics of immune response to vaccination, and novel insight into the flu response. The investigators will infer novel networks and pathways and as well as the dynamics of genes and mechanisms involved in asthma, flu vaccination, and individual responses, and correlate them to evaluated personalized genetic risks in the same study. The investigators will be able to also contrast the vaccination response in asthmatic and non-asthmatic individuals, in a longitudinal approach which has never been performed before using multiple-omics that included an immunization response.

Asthma pathogenesis and exacerbations have been associated to multiple risk factors, particularly respiratory viruses. In children respiratory syncytial viruses (RSVs) may induce bronchiolitis, and Human Rhinoviruses (HRVs) also may induce wheezing illnesses. RSVs and HRVs are age dependent risk factors for asthma, with the influenza virus also considered a prominent risk factor in adults. The Center for Disease Control recommends influenza vaccination in asthmatics annually. Both HRV and RSV infections were detected in a pilot integrative personal omics investigation, and provided a unique temporal expression signature in the non-asthmatic subject, with the involvement of a common set of antigen and defense response genes, as well as immune related pathways. These observed patterns in addition to the results of the vaccination study will be used as a guide, to find differences in healthy versus asthmatic patients' pathway activations which will provide insights into the genes and mechanisms involved in asthma pathogenesis and immune response to influenza vaccination. The twin paradigm will allow us to control for multiple confounding factors and focus on the individual genetic and possible epigenetic variation. The investigators will be able to infer novel networks and pathways and get into the genes and mechanisms involved in asthma, flu vaccination, and individual responses, while evaluating personalized genetic risks compared to medical history in the same study. Our primary investigation involves integrative multi-omics monitoring of individual monozygotic twins, healthy or discordant for asthma, following their flu vaccination, over a period of two annual vaccination cycles. The investigators will be collecting blood samples from monozygotic twin volunteers, for multiple time-points post influenza vaccination. The measurements will be repeated the following year after a second vaccination. Genomic sequencing will be used to evaluate the volunteer's genomic risks based on variants with known disease association. Full transcriptome (via RNA-Sequencing), proteome and metabolome profiling (via mass spectrometry) will be performed per time-point, as well as cytokine profiling. This will allow the dynamic monitoring of thousands of molecular components and their responses to vaccination, capturing both the initial innate response reaction in addition to the adaptive response and return to baseline. The study involves following responses in blood and saliva components after influenza vaccination. Two annual vaccinations will be considered, one per year for 2 years, and at 8 time points samples will be collected. This study involves a simple blood draw, saliva collection, standard FDA-approved influenza vaccine administration and Spirometry.