tetano
Editor, Senior Moderator
Cell Rep
. 2021 Oct 5;109838.
doi: 10.1016/j.celrep.2021.109838. Online ahead of print.
In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential
Brandon Lam[SUP] 1 [/SUP], Yu Jui Kung[SUP] 2 [/SUP], John Lin[SUP] 2 [/SUP], Ssu-Hsueh Tseng[SUP] 2 [/SUP], Ya Chea Tsai[SUP] 2 [/SUP], Liangmei He[SUP] 2 [/SUP], Gianni Castiglione[SUP] 3 [/SUP], Emily Egbert[SUP] 4 [/SUP], Elia J Duh[SUP] 3 [/SUP], Evan M Bloch[SUP] 2 [/SUP], Aaron A R Tobian[SUP] 2 [/SUP], Aaron M Milstone[SUP] 5 [/SUP], Richard B S Roden[SUP] 6 [/SUP], Tzyy-Choou Wu[SUP] 7 [/SUP], Chien-Fu Hung[SUP] 8 [/SUP]
Affiliations
Abstract
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads, variants with enhanced virulence and transmissibility have emerged. Although in vitro systems allow 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 coronavirus disease 2019 (COVID-19)+ or vaccinated antibody isotypes, titers, variant receptor binding domain (RBD) binding, and neutralization potential are studied, revealing numerous significant correlations. Immune escape of the K417N + E484K variant is observed because 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 animals receiving high-antibody-tier plasma, a phenomenon that can only be appreciated in vivo.
Keywords: COVID-19; N501Y; SARS-CoV-2; immune escape; in vivo modeling; pseudovirus.
. 2021 Oct 5;109838.
doi: 10.1016/j.celrep.2021.109838. Online ahead of print.
In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential
Brandon Lam[SUP] 1 [/SUP], Yu Jui Kung[SUP] 2 [/SUP], John Lin[SUP] 2 [/SUP], Ssu-Hsueh Tseng[SUP] 2 [/SUP], Ya Chea Tsai[SUP] 2 [/SUP], Liangmei He[SUP] 2 [/SUP], Gianni Castiglione[SUP] 3 [/SUP], Emily Egbert[SUP] 4 [/SUP], Elia J Duh[SUP] 3 [/SUP], Evan M Bloch[SUP] 2 [/SUP], Aaron A R Tobian[SUP] 2 [/SUP], Aaron M Milstone[SUP] 5 [/SUP], Richard B S Roden[SUP] 6 [/SUP], Tzyy-Choou Wu[SUP] 7 [/SUP], Chien-Fu Hung[SUP] 8 [/SUP]
Affiliations
- PMID: 34648735
- DOI: 10.1016/j.celrep.2021.109838
Abstract
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads, variants with enhanced virulence and transmissibility have emerged. Although in vitro systems allow 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 coronavirus disease 2019 (COVID-19)+ or vaccinated antibody isotypes, titers, variant receptor binding domain (RBD) binding, and neutralization potential are studied, revealing numerous significant correlations. Immune escape of the K417N + E484K variant is observed because 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 animals receiving high-antibody-tier plasma, a phenomenon that can only be appreciated in vivo.
Keywords: COVID-19; N501Y; SARS-CoV-2; immune escape; in vivo modeling; pseudovirus.