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Structure and Function-based Design of Vaccine Antigens and Antiviral Immunotherapies

Project description

Designing novel vaccine antigens and antiviral immunotherapies

Vaccines are essential for combatting viral diseases. Viral glycoproteins play a major role in immunity as antigenic components of vaccines because they trigger immune responses. However, for many viruses, there is not enough biological knowledge to support the transformation of viral glycoproteins into effective vaccine antigens. To address this, the ERC-funded VaxVision project aims to investigate the structural dynamics and functional potential of certain viral glycoproteins to design effective antigens. Using nanobody repertoire screens, it will comprehensively map glycoprotein surfaces and epitopes. VaxVision will then use a novel deep learning approach to design glycoproteins with enhanced antigenic form, applying this method to dangerous viruses such as Hendra, Nipah, Lassa, tick-borne encephalitis and Borna disease virus.

Objective

Vaccines are critical in preventing viral diseases, and recent advances in vaccine development and delivery platforms have enhanced their reach and efficacy. Viral glycoproteins that mediate host cell entry are the primary target of the humoral immune response and thus the main antigenic component of vaccines. However, for many viruses, we lack fundamental biological insights that would easily allow transforming their glycoproteins into highly effective vaccine antigens.
In this proposal, I introduce a completely novel approach to thoroughly extract structural and functional insights of viral glycoproteins for rational design of superior antigens. By conducting nanobody repertoire screens, I will bypass common constraints encountered in antibody screening, such as immunodominance bias and redundancy. Contrasting with conventional techniques that narrowly target a limited selection of epitopes, my approach promises an exhaustive mapping of glycoprotein surfaces and epitopes. This paradigm shift enables antigen rather than antibody or nanobody characterization. By determining high-resolution cryoEM structures of nanobodies bound to glycoproteins in transitional states, we will understand their structural dynamics.
Equipped with these unparalleled insights, we will harness pioneering deep learning methods to computationally design glycoproteins with enhanced antigenic form and exposed neutralizing surfaces. I will showcase this method for viruses with high case fatality rates, including Hendra, Nipah, Lassa, Tick-borne encephalitis, and Borna disease viruses.
VaxVision is set to offer a comprehensive framework for the antigen design of these and genetically or structurally related viruses.
My work aims to capitalize on the unused potential for vaccine antigen improvement and will provide an innovative workflow for extracting mechanistic insights and leveraging them for vaccine antigen design, with the potential to drive vaccine innovations beyond just viral pathogens.

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Programme(s)

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-STG

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Host institution

KAROLINSKA INSTITUTET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 499 525,00
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 499 525,00

Beneficiaries (1)

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