Identification, structures and ontogenies of SARS-CoV-2 antibodies

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Tongqing  Zhou
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $427,403
Funding agency: National Institute of Allergy and Infectious Diseases

Though COVID-19 has been less disruptive than it used to be during the earlier waves of the pandemic, it has not been eradicated. Variants of the causative SARS-CoV-2 virus continue to emerge and evade neutralization by antibodies elicited by vaccination or natural infection of early variants. In the first study, we examined both innate immune responses (such as those from macrophages and dendritic cells) and adaptive responses (like antigen-specific peripheral T and B cells) triggered by the mRNA-1273 vaccine in non-human primates with a panel of staining cocktail consisting of antibodies and probes. This study provides a detailed analysis of the immune responses, confirming a lasting pro-inflammatory state, T cell activation, and B cell activation, to understand how these interactions contribute to vaccine efficacy. In a separate study, we investigated the effects of an adjuvanted SARS-CoV-2 spike protein vaccine on the generation of long-lived plasma cells in nonhuman primates and found such vaccination can induce a robust, long-lasting, cross-reactive neutralizing response against SARS-CoV-2. In a third study, we explored a high-affinity ACE2 antagonist designed to block SARS-CoV-2 from binding to its receptor ACE2 and inhibit viral replication. The antagonist suppresses virus replication in both upper and lower airways, demonstrating its effectiveness in limiting viral replication. The ACE2 antagonist showed effectiveness against a broad range of SARS-CoV-2 variants, indicating its potential as a "variant-proof" therapeutic option.

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