| Autor: |
Raquel Ortiz, Ana Barajas, Anna Pons-Grífols, Benjamin Trinité, Ferran Tarrés-Freixas, Carla Rovirosa, Víctor Urrea, Antonio Barreiro, Anna Gonzalez-Tendero, Maria Rovira-Rigau, Maria Cardona, Laura Ferrer, Bonaventura Clotet, Jorge Carrillo, Carmen Aguilar-Gurrieri, Julià Blanco |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Viruses, Vol 16, Iss 6, p 987 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1999-4915 |
| DOI: |
10.3390/v16060987 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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