CD8+ T cells mediate protection against Zika virus induced by an NS3-based vaccine
Zika virus (ZIKV) is associated with congenital malformations in infants born to infected mothers, and with Guillain-Barré syndrome in infected adults. Development of ZIKV vaccines has focused predominantly on the induction of neutralizing antibodies, although a suboptimal antibody response may theoretically enhance disease severity through antibody-dependent enhancement (ADE). Here, we report induction of a protective anti-ZIKV CD8+ T cell response in the HLA-B*0702 Ifnar1-/- transgenic mice using an alphavirus-based replicon RNA vaccine expressing ZIKV nonstructural protein NS3, a potent T cell antigen. The NS3 vaccine did not induce a neutralizing antibody response but elicited polyfunctional CD8+ T cells that were necessary and sufficient for preventing death in lethally infected adult mice and fetal growth restriction in infected pregnant mice. These data identify CD8+ T cells as the major mediators of ZIKV NS3 vaccine-induced protection and suggest a new strategy to develop safe and effective anti-flavivirus vaccines.
LUNAR®-CF, an aerosolized mRNA replacement Therapy for Cystic Fibrosis Lung Disease
LUNAR®-CF is an aerosolized mRNA replacement therapy to treat Cystic Fibrosis (CF) Lung Disease, a therapeutic approach agnostic to a patient’s genotype. A healthy copy of the human CFTR mRNA is encapsulated into lipid nanoparticles (LUNAR®-hCFTR), aerosolized to patient’s airways using a vibrating mesh nebulizer to directly deliver a de novo human CFTR mRNA into epithelial cells. This human CFTR mRNA encodes a fully functional human CFTR protein that will be beneficial to facilitate mucociliary clearance and improve CF lung disease.