Publications by authors named "V Chohan"

The recurring spillover of pathogenic coronaviruses and demonstrated capacity of sarbecoviruses, such SARS-CoV-2, to rapidly evolve in humans underscores the need to better understand immune responses to this virus family. For this purpose, we characterized the functional breadth and potency of antibodies targeting the receptor binding domain (RBD) of the spike glycoprotein that exhibited cross-reactivity against SARS-CoV-2 variants, SARS-CoV-1 and sarbecoviruses from diverse clades and animal origins with spillover potential. One neutralizing antibody, C68.

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Article Synopsis
  • The SARS-CoV-2 virus has evolved to evade immune responses created by vaccines and previous infections, particularly through mutations in the spike protein's receptor binding domain.
  • Researchers identified a group of S2 mAbs from convalescent individuals that target various regions in the spike protein, including one powerful mAb, C20.119, which effectively neutralizes multiple SARS-CoV-2 variants.
  • Some mAbs displayed antibody-dependent cellular cytotoxicity (ADCC) and targeted regions of the spike protein that could lead to effective treatments, suggesting potential for developing new therapies for future pandemics.
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Article Synopsis
  • The study highlights the need to understand immune responses to pathogenic coronaviruses, particularly in the context of rapid evolution, using antibodies targeting the receptor binding domain (RBD) of the spike glycoprotein.
  • An antibody named C68.61 was identified for its exceptional ability to neutralize SARS-CoV-2 variants as well as other sarbecoviruses without leading to escape variants, indicating a conserved target epitope.
  • The research also discovered 11 additional cross-reactive antibodies that can potentially serve as therapeutic options for pandemic preparedness by recognizing conserved regions across multiple sarbecoviruses.
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The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines.

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Human natural history and vaccine studies support a protective role of antibody dependent cellular cytotoxicity (ADCC) activity against many infectious diseases. One setting where this has consistently been observed is in HIV-1 vertical transmission, where passively acquired ADCC activity in HIV-exposed infants has correlated with reduced acquisition risk and reduced pathogenesis in HIV+ infants. However, the characteristics of HIV-specific antibodies comprising a maternal plasma ADCC response are not well understood.

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