Addressing the unmet need for the West Nile virus control

A unique approach to develop immunogens to protect against the virus

In search of a broad immunity

Combining the two major arms of the immune response: humoral and cellular

At LWNVIVAT, we will use computational tools to analyse sequential variability of WNV and design immunogens based on conserved E glycoprotein regions that elicit highly-specific neutralising antibodies and does not induce cross-reactivity responses against other flaviviruses. We will also develop Virus Like Particles and antibodies as adjuvants to enhance vaccine efficacy. In addition, we will seek for a cellular response to ensure a long-lasting protection.

Testing the immunity

An evaluation of protective responses in human and animal samples in vitro and in vivo in preclinical models

Selected immunogens will be tested using in vitro assays with human blood cells and tonsil organoids to evaluate humoral and cellular immunogenicity. We will also use in vivo assays in preclinical models that elicit an immune response akin to that observed in humans, with the objective to understand the efficacy of the molecules in a context more closely resembling practical conditions.Selected antibodies will be evaluated for their prophylactic activity but also as a therapeutic option.

The potential impact of our project

Striving for a better health

Our project is funded by the Horizon Europe programme until 2027 and we are working to provide a vaccine candidate against WNV. If the vaccine is successful, morbidity and mortality associated with the WNV infection could be reduced. Prevention and reduction of future outbreaks of the virus could also benefit public health, especially where WNV is endemic, such as Southern and Eastern Europe and the US. Our project may also guide the development of effective vaccines against other viruses, particularly flaviviruses.

Work Packages

Design of novel structure stabilized immunogens against WNV based on B-cell and T-cell epitope constructs

Objectives: We will conduct a large-scale analysis of WNV proteome based on genomics, proteomics, bioinformatics and machine learning techniques to identify key viral antigens and epitopes able to trigger a protective immune response.

WP leader: BSC-CNS

Participant entities: HIPRA, IrsiCaixa

Production, purification and characterization of recombinant E immunogens

Objectives: The main objective of WP2 is the high-quality production and characterization of WNV recombinant proteins identified and designed in WP1.

WP leader: CRG

Participant entities: HIPRA, IRSICAIXA

Production and purification of VLP containing selected immunogens

Objective: The main objective of WP3 is the development of vaccine formulations of highly immunogenic Virus like particles displaying selected WNV targets. Two main strategies of VLP formulation will be followed, one seeking to increase the density of the antigens on the surface of retroviral particles and the other mimicking authentic WNV particles.

WP leader: TUBS

Participant entities: HIPRA, IRSICAIXA

In vitro immunogenicity prediction of WNV proteins-candidates combining tonsil organoids and peripheral blood cells

Objective: The WP4 aim to evaluate the immunogenicity of WNV proteins candidates as antigens for vaccine development. Here, WP4 will combine in vitro testing of protein candidates in both human tonsil organoids and peripheral blood cells to provide the required information of antigen immunogenicity and to generate novel information on the mechanistic insight in the priming of immune responses against WNV candidates in humans.

WP leader: IrsiCaixa

Participant entities: UCPH

In vivo immunogenicity studies

Objective: The aim of this WP is to define the immunogenicity of the vaccine prototypes (recombinant proteins and VLPs) designed, selected and produced in WP1, WP2 and WP3. Furthermore, we will define the optimal adjuvant system for the induction of long-lasting antibody responses in a preclinical model.

WP leader: IrsiCaixa

Participant entities: HIPRA, UM

Generation of novel anti-E monoclonal antibodies

Objective: The main objective of WP6 is the development of antibodies against WNV surface proteins. These antibodies will be used for informing about neutralizing and non-neutralizing epitopes, for the in vivo efficacy studies, and to evaluate their adjuvant-like effect, enhancing the immune response to a defined immunogen.

WP leader: TUBS

Participant entities: IrsiCaixa

In vivo efficacy studies

Objective: The objective of the WP7 is to define the effectiveness of candidate vaccines- and selected antibodies activity in prophylactic and therapeutic approaches in a mouse model of WNV infection.

WP leader: UM

Participant entities: INSERN

Regulatory activities and GMP manufacturing plan

Objective: The main objective of this work package is to provide scientific and regulatory support, and industrial guidance during the development of the WNV vaccine prototypes, with special focus on the manufacturability and industrial scale up of vaccine candidates according to regulatory requirements.

WP leader: HIPRA

Participant entities: IrsiCaixa, BSC, CRG

Communication, dissemination and exploitation

Objective: The main objective of this work package is to establish and execute a protection strategy of the results towards exploitation and to develop a business plan to ensure the exploitation of the different results of WNV vaccine prototype project. Moreover, a dissemination and communication strategy will be defined in collaboration with the consortium partners. Finally, Responsible Research and Innovation (RRI) activities, focused on the improvement of vaccine acceptation by the society, will be performed.