Bette Korber - August 26, 2020

Bette Korber, PhD, Laboratory Fellow, Los Alamos National Laboratory, "The D614G mutation in Spike: increased infectivity and neutralizing antibody sensitivity and the underlying mechanism"

The talk started with the introduction of G614, which is a part of the G clade that came out of Europe and has been followed by GISAID since early spring. Epidemiological evidence showed that G514 is more transmissible, especially, the recurring increases in frequency are not consistent with founder effects. The research study showed that RBD antibodies can be more potent against G614 than D614. The D614G mutant Spike prefers the “one up” conformation which allows ACE2 interactions and exposes the RBD epitope regions. The research followed the procedure that systematically extracted all GISAID regional data where both forms were co-circulating, there was enough time to see a change, and there were enough sequences for statistical assessment. A comprehensive and global search of all geographic regions in GISAD continued to show that the G form almost always became dominant at every level, continent, country, state, city. If random founder effects were driving shifts in population, these founder effects would not always go towards the G form. To summarize, more research needs to understand the biology of this virus. The virus is different and more transmissible than it was when the world began to shelter in place mid-March. Specifically, G614 is in itself an inspiration for greater caution, which could help inform epidemiological models. Finally, more research is needed to know the impact of G614 on vaccines and therapeutics. G614 is sensitive to polyclonal antibodies from sera, more sensitive to D614 vaccine raised Nabs than is D614. G614’s greater infectivity makes it easier to use in a pseudovirus assay than D614. G614 may be useful as a vaccine antigen because the RBD, a key neutralizing target, is more exposed.