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 in mammalian cells. In different mammalian cell lines the protein follows the same folding pathway with identical folding intermediates, but folds with very different kinetics. To examine the effect of cellular context 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 more efficiently, still via the same folding intermediates as in vertebrate cells. Our results suggest that insect cells provide a highly efficient and effective folding environment for influenza virus HA and the ideal production platform for HA (emergency) vaccines.