In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential

Lam, Brandon; Kung, Yu Jui; Lin, John; Tseng, Ssu-Hsueh; Tsai, Ya Chea; He, Liangmei; Castiglione, Gianni; Egbert, Emily; Duh, Elia J.; Bloch, Evan M.; Tobian, Aaron A.R.; Milstone, Aaron M.; Roden, Richard B.S.; Wu, T. C.; Hung, Chien-Fu

As SARS-CoV-2 spreads, variants with enhanced virulence and transmissibility have emerged. While in vitro systems allow for rapid characterization, they do not fully recapitulate the dynamic interaction of virions and neutralizing antibodies in the airway. Here, we demonstrate that the N501Y variant permits respiratory infection in unmodified mice. We utilize N501Y to survey in vivo pseudovirus infection dynamics and susceptibility to reinfection with the L452R (Los Angeles), K417N + E484K (South Africa), and L452R + K417N + E484Q (India) variants. Human COVID-19+ or vaccinated antibody isotypes, titers, variant RBD binding, and neutralization potential are studied, revealing numerous significant correlations. Immune escape of the K417N + E484K variant is observed, as infection can be appreciated in the nasopharynx, but not lungs, of mice transferred with low antibody-tier plasma. Conversely, near-complete protection is observed in the animals receiving high antibody-tier plasma, a phenomenon that can only be appreciated in vivo.