Production and Immunogenicity of FeLV Gag-Based VLPs Exposing a Stabilized FeLV Envelope Glycoprotein
Ortiz, Raquel (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Barajas Vélez, Ana (Universitat de Vic)
Pons-Grífols, Anna (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Trinité, Benjamin (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Tarrés-Freixas, Ferran (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Rovirosa, Carla (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Urrea, Víctor (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Barreiro Vázquez, Antonio (HIPRA (Amer, Catalunya))
Gonzalez-Tendero, Anna (HIPRA (Amer, Catalunya))
Rovira-Rigau, Maria (HIPRA (Amer, Catalunya))
Cardona, Maria (HIPRA (Amer, Catalunya))
Ferrer, Laura (HIPRA (Amer, Catalunya))
Clotet Sala, Bonaventura (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Carrillo, Jorge (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Aguilar-Gurrieri, Carmen (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Blanco, Julià (Centro de Investigación Biomédica en Red de Enfermedades Infecciosas)

Data:	2024
Resum:	The envelope glycoprotein (Env) of retroviruses, such as the Feline leukemia virus (FeLV), is the main target of neutralizing humoral response, and therefore, a promising vaccine candidate, despite its reported poor immunogenicity. The incorporation of mutations that stabilize analogous proteins from other viruses in their prefusion conformation (e. g. , HIV Env, SARS-CoV-2 S, or RSV F glycoproteins) has improved their capability to induce neutralizing protective immune responses. Therefore, we have stabilized the FeLV Env protein following a strategy based on the incorporation of a disulfide bond and an Ile/Pro mutation (SOSIP) previously used to generate soluble HIV Env trimers. We have characterized this SOSIP-FeLV Env in its soluble form and as a transmembrane protein present at high density on the surface of FeLV Gag-based VLPs. Furthermore, we have tested its immunogenicity in DNA-immunization assays in C57BL/6 mice. Low anti-FeLV Env responses were detected in SOSIP-FeLV soluble protein-immunized animals; however, unexpectedly no responses were detected in the animals immunized with SOSIP-FeLV Gag-based VLPs. In contrast, high humoral response against FeLV Gag was observed in the animals immunized with control Gag VLPs lacking SOSIP-FeLV Env, while this response was significantly impaired when the VLPs incorporated SOSIP-FeLV Env. Our data suggest that FeLV Env can be stabilized as a soluble protein and can be expressed in high-density VLPs. However, when formulated as a DNA vaccine, SOSIP-FeLV Env remains poorly immunogenic, a limitation that must be overcome to develop an effective FeLV vaccine.
Ajuts:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00452
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Env ; Vaccine ; Virus-like particle (VLP) ; FeLV ; SOSIP ; Veterinary science
Publicat a:	Viruses, Vol. 16 (june 2024) , ISSN 1999-4915

DOI: 10.3390/v16060987
PMID: 38932278

14 p, 1.9 MB

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