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Evaluating Antibody Mediated Protection against Alpha, Beta, and Delta SARS-CoV-2 Variants of Concern in K18-hACE2 Transgenic Mice

Evaluating Antibody Mediated Protection against Alpha, Beta, and Delta SARS-CoV-2 Variants of Concern in K18-hACE2 Transgenic Mice

Authors :
Ting Y. Wong
Alexander M. Horspool
Brynnan P. Russ
Chengjin Ye
Katherine S. Lee
Michael T. Winters
Justin R. Bevere
Olivia A. Miller
Nathaniel A. Rader
Melissa Cooper
Theodore Kieffer
Julien Sourimant
Alexander L. Greninger
Richard K. Plemper
James Denvir
Holly A. Cyphert
Mariette Barbier
Jordi B. Torrelles
Ivan Martinez
Luis Martinez-Sobrido
F. Heath Damron
Source :
Journal of Virology. 96
Publication Year :
2022
Publisher :
American Society for Microbiology, 2022.

Abstract

SARS-CoV-2 variants of concern (VoC) are impacting responses to the COVID-19 pandemic. Here, we utilized passive immunization using human convalescent plasma (HCP) obtained from a critically ill COVID-19 patient in the early pandemic to study the efficacy of polyclonal antibodies generated to ancestral SARS-CoV-2 against the Alpha, Beta, and Delta VoC in the K18 human angiotensin converting enzyme 2 (hACE2) transgenic mouse model. HCP protected mice from challenge with the original WA-1 SARS-CoV-2 strain; however, only partially protected mice challenged with the Alpha VoC (60% survival) and failed to save Beta challenged mice from succumbing to disease. HCP treatment groups had elevated receptor binding domain (RBD) and nucleocapsid IgG titers in the serum; however, Beta VoC viral RNA burden in the lung and brain was not decreased due to HCP treatment. While mice could be protected from WA-1 or Alpha challenge with a single dose of HCP, six doses of HCP could not decrease mortality of Delta challenged mice. Overall, these data demonstrate that VoC have enhanced immune evasion and this work underscores the need for

Details

ISSN :
10985514 and 0022538X
Volume :
96
Database :
OpenAIRE
Journal :
Journal of Virology
Accession number :
edsair.doi.dedup.....2b79849e969f4db9ec0604d47bf75cdd
Full Text :
https://doi.org/10.1128/jvi.02184-21