Biology subjects

Doria-Rose, N.

Publications and source records attributed to Doria-Rose, N..

2 recordsLinked to original sources

bioRxiv2021

Isolation and Characterization of Cross-Neutralizing Coronavirus Antibodies from COVID-19+ Subjects

SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterized 198 antibodies isolated from four COVID19+ subjects and identified 14 SARS-CoV-2 neutralizing antibodies. One targeted the NTD, one recognized an epitope in S2 and twelve bound the RBD. Three anti-RBD neutralizing antibodies cross-neutralized SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency rather than the antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. The anti-S2 antibody also neutralized SARS-CoV-1 and all four cross-neutralizing antibodies neutralized the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.

immunology↗

bioRxiv2021

Rapid selection of HIV envelopes that bind to neutralizing antibody B cell lineage members with functional improbable mutations

Elicitation of broadly neutralizing antibodies (bnAbs) by an HIV vaccine will involve priming the immune system to activate antibody precursors, followed by boosting immunizations to select for antibodies with functional features required for neutralization breadth. The higher the number of acquired mutations necessary for function, the more convoluted are the antibody developmental pathways. HIV bnAbs acquire a large number of somatic mutations, but not all mutations are functionally important. Here we identified a minimal subset of mutations sufficient for the function of the naturally occurring V3-glycan bnAb DH270.6. Using antibody library screening, candidate envelope immunogens that interacted with DH270.6-like antibodies containing this set of key mutations were identified and selected in vitro. Our results demonstrate that less complex B cell evolutionary pathways than those naturally observed exist for the induction of HIV bnAbs by vaccination, and establish rational approaches to identify boosting sequential envelope candidate immunogens.

immunology↗