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1.
Sci Immunol ; : eabl9943, 2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1909566

ABSTRACT

Monoclonal antibodies are an efficacious therapy against SARS-CoV-2. However, rapid viral mutagenesis, led to escape from most of these therapies, outlining the need for an antibody cocktail with a broad neutralizing potency. Using an unbiased interrogation of the memory B cell repertoire of convalescent COVID-19 patients, we identified human antibodies with broad antiviral activity in vitro and efficacy in vivo against all tested SARS-CoV-2 variants of concern, including Delta, Omicron BA.1 and BA.2. Here, we describe an antibody cocktail IMM-BCP-01, that consists of three patient-derived broadly neutralizing antibodies directed at non-overlapping surfaces on the SARS-CoV-2 spike protein. Two antibodies, IMM20184 and IMM20190, directly blocked Spike binding to the ACE2 receptor. Binding of the third antibody, IMM20253, to its cryptic epitope on the outer surface of RBD, altered the conformation of the Spike Trimer, promoting release of Spike monomers. These antibodies decreased Omicron SARS-CoV-2 infection in the lungs of Syrian golden hamsters in vivo, and potently induced antiviral effector response in vitro, including phagocytosis, ADCC, and complement pathway activation. Our pre-clinical data demonstrated that the three antibody cocktail IMM-BCP-01 could be a promising means for preventing or treating infection of SARS-CoV-2 variants of concern, including Omicron BA.1 and BA.2, in susceptible individuals.

2.
Clin Infect Dis ; 74(6): 1081-1084, 2022 03 23.
Article in English | MEDLINE | ID: covidwho-1707490

ABSTRACT

The clinical significance of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) RNA in stool remains uncertain. We found that extrapulmonary dissemination of infection to the gastrointestinal tract, assessed by the presence of SARS-CoV-2 RNA in stool, is associated with decreased coronavirus disease 2019 (COVID-19) survival. Measurement of SARS-CoV-2 RNA in stool may have utility for clinical risk assessment.


Subject(s)
COVID-19 , SARS-CoV-2 , Feces , Gastrointestinal Tract , Humans , RNA, Viral , SARS-CoV-2/genetics
3.
Cell ; 184(19): 4969-4980.e15, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1333275

ABSTRACT

Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded antibodies from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found seven major antibody competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of antibody-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. Although emerging SARS-CoV-2 variants of concern escaped binding by many members of the groups associated with the most potent neutralizing activity, some antibodies in each of those groups retained affinity-suggesting that otherwise redundant components of a primary immune response are important for durable protection from evolving pathogens. Our results furnish a global atlas of S-specific memory B cell repertoires and illustrate properties driving viral escape and conferring robustness against emerging variants.

4.
Clin Infect Dis ; 74(6): 1081-1084, 2022 03 23.
Article in English | MEDLINE | ID: covidwho-1303899

ABSTRACT

The clinical significance of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) RNA in stool remains uncertain. We found that extrapulmonary dissemination of infection to the gastrointestinal tract, assessed by the presence of SARS-CoV-2 RNA in stool, is associated with decreased coronavirus disease 2019 (COVID-19) survival. Measurement of SARS-CoV-2 RNA in stool may have utility for clinical risk assessment.


Subject(s)
COVID-19 , SARS-CoV-2 , Feces , Gastrointestinal Tract , Humans , RNA, Viral , SARS-CoV-2/genetics
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