Discovery and Optimization of Broadly Protective Merbecovirus Neutralizing Antibodies
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) infection has the highest mortality rate (36%) of any of the known human-pathogenic Betacoronaviruses. MERS-CoV continues to circulate in the Middle East, and due to global travel has spread to 27 other countries making it a global health priority. A number of viruses related to MERS-CoV have been identified in mammals worldwide, and several have been found to utilize human DPP4- or ACE2-receptors for cell entry. Therefore, the MERS-related betacoronaviruses (Merbecoviruses, MERBs) have considerable zoonotic potential. While many medical countermeasures like vaccines and antibody therapeutics were developed to fight SARS-CoV-2, these countermeasures do not prevent disease caused by MERBs. The long-term goal of this proposal is to generate such MERB broadly neutralizing antibody (bnAb) therapeutics. The significance of this project includes the identification of broadly protective antibodies (Abs) and their epitopes, enabling rational design of antibody-based therapeutics and vaccines against a deadly virus. While previous research has focused on identifying potent neutralizing antibodies against MERS-CoV, no antibodies have been shown to be cross- protective against MERS-CoV and other MERBs. In preliminary studies in vaccinated rhesus macaques (RMs), we elicited robust cross-binding and cross-neutralizing plasma Abs against multiple MERBs. Post- vaccination RM B cells bound both MERS-CoV receptor binding domain (RBD) and bat MERS-CoV-related virus NL140422 RBD. Individual Abs from these RMs bound to as many as 7 different MERS-CoV-related RBDs and MERS-CoV. The objectives of this study are to 1) determine the neutralization breadth of monoclonal nAbs from these vaccinated RMs, 2) determine the critical features of the binding interface between cross-reactive nAb and virus spike RBD, and 3) determine the cross-protective efficacy of the mAbs. The innovations of this project include human, bat, and pangolin live-virus MERB models (MERS-CoV, PDF2180, NL140422 (MERS 422), MjHKU4r, HKU-5), 13 genetically diverse MERB spike and RBD antigens, MERS-CoV and MjHKU4 mouse challenge models, and the use of a machine-learning Ab optimization to improve natural Abs. The impact of this project includes the demonstration that vaccination can elicit broad MERB nAbs against multiple conserved epitopes, the development of trispecific immunotherapies, and the definition of bnAb epitopes that inform rational design of immunogens targeting cross-protective B cells. Our Abs will be potential tools to combat MERS-CoV outbreaks and prepare for future outbreaks from pre- emergent MERBs.
Grant Summary
Discovery and Optimization of Broadly Protective Merbecovirus Neutralizing Antibodies is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $830K for university, nonprofit, healthcare org. Applications are due 2031-03-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $830K
2031-03-31
- 1Confirm your organization is eligible for Discovery and Optimization of Broadly Protective Merbecovirus Neutralizing Antibodies from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIAID - National Institute of Allergy and Infectious Diseases before the deadline.
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Discovery and Optimization of Broadly Protective Merbecovirus Neutralizing Antibodies: Frequently Asked Questions
Who is eligible for the Discovery and Optimization of Broadly Protective Merbecovirus Neutralizing Antibodies?
Discovery and Optimization of Broadly Protective Merbecovirus Neutralizing Antibodies is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Discovery and Optimization of Broadly Protective Merbecovirus Neutralizing Antibodies provide?
Discovery and Optimization of Broadly Protective Merbecovirus Neutralizing Antibodies provides up to $830K per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Discovery and Optimization of Broadly Protective Merbecovirus Neutralizing Antibodies deadline?
Applications for Discovery and Optimization of Broadly Protective Merbecovirus Neutralizing Antibodies are due 2031-03-31 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Discovery and Optimization of Broadly Protective Merbecovirus Neutralizing Antibodies?
To apply for Discovery and Optimization of Broadly Protective Merbecovirus Neutralizing Antibodies, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.