{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wong TY"],"funding":["NIAID NIH HHS","NIH HHS","NIGMS NIH HHS","WV High Education Policy Commission"],"pagination":["e0218421"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8941865"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["96(6)"],"pubmed_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 <i>in vivo</i> models to evaluate future emerging strains. <b>IMPORTANCE</b> Emerging SARS-CoV-2 VoC are posing new problems regarding vaccine and monoclonal antibody efficacy. To better understand immune evasion tactics of the VoC, we utilized passive immunization to study the effect of early-pandemic SARS-CoV-2 HCP against, Alpha, Beta, and Delta VoC. We observed that HCP from a human infected with the original SARS-CoV-2 was unable to control lethality of Alpha, Beta, or Delta VoC in the K18-hACE2 transgenic mouse model of SARS-CoV-2 infection. Our findings demonstrate that passive immunization can be used as a model to evaluate immune evasion of emerging VoC strains."],"journal":["Journal of virology"],"pubmed_title":["Evaluating Antibody Mediated Protection against Alpha, Beta, and Delta SARS-CoV-2 Variants of Concern in K18-hACE2 Transgenic Mice."],"pmcid":["PMC8941865"],"funding_grant_id":["P20 GM121322","Research Challenge Grant","S10 OD016165","R43 AI165089","P20 GM103434","R01 AI161363","R01 AI161175"],"pubmed_authors":["Cooper M","Martinez-Sobrido L","Russ BP","Ye C","Torrelles JB","Miller OA","Bevere JR","Kieffer T","Wong TY","Cyphert HA","Martinez I","Lee KS","Plemper RK","Horspool AM","Rader NA","Winters MT","Denvir J","Sourimant J","Barbier M","Damron FH","Greninger AL"],"additional_accession":[]},"is_claimable":false,"name":"Evaluating Antibody Mediated Protection against Alpha, Beta, and Delta SARS-CoV-2 Variants of Concern in K18-hACE2 Transgenic Mice.","description":"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 <i>in vivo</i> models to evaluate future emerging strains. <b>IMPORTANCE</b> Emerging SARS-CoV-2 VoC are posing new problems regarding vaccine and monoclonal antibody efficacy. To better understand immune evasion tactics of the VoC, we utilized passive immunization to study the effect of early-pandemic SARS-CoV-2 HCP against, Alpha, Beta, and Delta VoC. We observed that HCP from a human infected with the original SARS-CoV-2 was unable to control lethality of Alpha, Beta, or Delta VoC in the K18-hACE2 transgenic mouse model of SARS-CoV-2 infection. Our findings demonstrate that passive immunization can be used as a model to evaluate immune evasion of emerging VoC strains.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2025-04-22T09:52:52.287Z","creation":"2025-04-05T23:15:12.268Z"},"accession":"S-EPMC8941865","cross_references":{"pubmed":["35080423"],"doi":["10.1128/jvi.02184-21"]}}