VLPs generated by the fusion of RSV-F or hMPV-F glycoprotein to HIV-Gag show improved immunogenicity and neutralizing response in mice

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccines have been long overdue. Structure-based vaccine design created a new momentum in the last decade, and the first RSV vaccines have finally been approved in older adults and pregnant individuals. These vaccines are based on re...

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Detalles Bibliográficos
Autores: Trinité, Benjamin|||0000-0003-3809-042X, Durr, Eberhard|||0000-0003-0601-1117, Pons-Grífols, Anna|||0000-0002-8402-3941, O'Donnell, Gregory, Aguilar-Gurrieri, Carmen|||0000-0002-5701-7650, Rodriguez, Silveria, Urrea, Víctor|||0000-0002-2577-856X, Tarrés-Freixas, Ferran|||0000-0002-1569-0126, Mane, Joel, Ortiz, Raquel|||0000-0002-6919-2026, Rovirosa, Carla|||0000-0002-7111-0253, Carrillo, Jorge|||0000-0003-0221-5948, Clotet Sala, Bonaventura|||0000-0003-3232-4598, Zhang, Lan, Blanco, Julià|||0000-0002-2225-0217
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:311579
Acceso en línea:https://ddd.uab.cat/record/311579
https://dx.doi.org/urn:doi:10.1016/j.vaccine.2024.04.048
Access Level:acceso abierto
Palabra clave:Respiratory syncytial virus
Human metapneumovirus
Vaccine
HIV Gag
Fusion protein
Virus lies particles
Immunogenicity
Neutralizing antibodies
Descripción
Sumario:Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccines have been long overdue. Structure-based vaccine design created a new momentum in the last decade, and the first RSV vaccines have finally been approved in older adults and pregnant individuals. These vaccines are based on recombinant stabilized pre-fusion F glycoproteins administered as soluble proteins. Multimeric antigenic display could markedly improve immunogenicity and should be evaluated in the next generations of vaccines. Here we tested a new virus like particles-based vaccine platform which utilizes the direct fusion of an immunogen of interest to the structural human immunodeficient virus (HIV) protein Gag to increase its surface density and immunogenicity. We compared, in mice, the immunogenicity of RSV-F or hMPV-F based immunogens delivered either as soluble proteins or displayed on the surface of our VLPs. VLP associated F-proteins showed better immunogenicity and induced superior neutralizing responses. Moreover, when combining both VLP associated and soluble immunogens in a heterologous regimen, VLP-associated immunogens provided added benefits when administered as the prime immunization.

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