Folding of influenza virus hemagglutinin in insect cells is fast and efficient

Folding of influenza virus hemagglutinin (HA) in the endoplasmic reticulum has been well defined inmammalian cells. In different mammalian cell lines the protein follows the same folding pathway withidentical folding intermediates, but folds with very different kinetics. To examine the effect of cellularcontext on HA folding and to test to which extent insect cells would support the HA folding process,we expressed HA in Sf9 insect cells. Strikingly, in this invertebrate system HA folded faster and moreefficiently, still via the same folding intermediates as in vertebrate cells. Our results suggest that insectcells provide a highly efficient and effective folding environment for influenza virus HA and the idealproduction platform for HA (emergency) vaccines.