| Autor: |
Ortiz R; IrsiCaixa, 08916 Badalona, Spain.; Doctorate School, Microbiology Department, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Barajas A; IrsiCaixa, 08916 Badalona, Spain.; Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Spain., Pons-Grífols A; IrsiCaixa, 08916 Badalona, Spain.; Doctorate School, Microbiology Department, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Trinité B; IrsiCaixa, 08916 Badalona, Spain., Tarrés-Freixas F; IrsiCaixa, 08916 Badalona, Spain., Rovirosa C; IrsiCaixa, 08916 Badalona, Spain., Urrea V; IrsiCaixa, 08916 Badalona, Spain., Barreiro A; HIPRA, 17170 Amer, Spain., Gonzalez-Tendero A; HIPRA, 17170 Amer, Spain., Rovira-Rigau M; HIPRA, 17170 Amer, Spain., Cardona M; HIPRA, 17170 Amer, Spain., Ferrer L; HIPRA, 17170 Amer, Spain., Clotet B; IrsiCaixa, 08916 Badalona, Spain.; Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Spain.; Infectious Diseases Department, Germans Trias I Pujol Hospital, 08916 Badalona, Spain., Carrillo J; IrsiCaixa, 08916 Badalona, Spain., Aguilar-Gurrieri C; IrsiCaixa, 08916 Badalona, Spain., Blanco J; IrsiCaixa, 08916 Badalona, Spain.; Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Spain.; Germans Trias I Pujol Research Institute (IGTP), 08916 Badalona, Spain.; CIBERINFEC, ISCIII, 28029 Madrid, Spain. |
| Abstrakt: |
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. |
