A safe and effective live-attenuated JUNV vaccine is licensed in Argentina and has been used with success within the JUNV endemic area to prevent AHF. However, the documented genetic and virulence heterogeneity of Candid#1, and the lack of understanding of the mechanisms underlying Candid#1 attenuation pose great barriers to its acceptance in the United States. Compared with its parental, as well as with other virulent JUNV strains, Candid#1 contains multiple amino acid changes in GP, NP and L that hinder the identification of the genetic markers of attenuation. Asthma is a complex disease caused by gene-gene and geneenvironment interactions. Many asthma susceptibility genes have been identified, several of which are expressed in the airway epithelium. The airway epithelium in asthma has a disrupted barrier function and an impaired repair response upon injury that might contribute to airway remodelling. In addition, the airway epithelium of asthmatics shows an enhanced immune response towards harmful agents by secreting increased Sphingosine-1-phosphate amounts of pro-inflammatory mediators such as IL-33, CCL20, GM-CSF or TSLP. Polymorphisms in asthma susceptibility genes expressed by airway epithelial cells, affecting the level or regulation of their expression, might therefore contribute to both altered barrier function of airway epithelial cells and to enhanced induction of an immune response upon airway epithelial injury. Previously, we identified protocadherin-1 as a novel susceptibility gene for airway hyperresponsiveness in asthma families. Interestingly, a strong linkage signal of PCDH1 with asthma and AHR was observed in S4 families exposed to environmental tobacco smoke. PCDH1 encodes for two main isoforms: a 3 exon and a 5 exon isoform that are expressed in the airway epithelium. In addition a putative third isoform was identified that lacks exon 1 and part of exon 2. Both main isoforms encode a protein containing an extracellular domain with seven cadherin repeats, a transmembrane domain, and an intracellular domain containing several Serine and Tyrosine residues, that have been found to be subject to phosphorylation. The third isoform only contains two extracellular cadherin repeats and the shared intracellular domain. In addition, both isoforms 2 and 3 encode an additional intracellular domain containing three intracellular conserved motifs, of which CM3 is the binding motif for protein phosphatase 1 alpha.