Production and Immunogenicity of FeLV Gag-Based VLPs Exposing a Stabilized FeLV Envelope Glycoprotein
Por:
Ortiz, R, Barajas, A, Pons-Grífols, A, Trinité, B, Tarrés-Freixas, F, Rovirosa, C, Urrea, V, Barreiro, A, Gonzalez-Tendero, A, Rovira-Rigau, M, Cardona, M, Ferrer, L, Clotet, B, Carrillo, J, Aguilar-Gurrieri, C and Blanco, J
Publicada:
1 jun 2024
Resumen:
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.
Filiaciones:
:
IrsiCaixa, Badalona 08916, Spain
Univ Autonoma Barcelona, Doctorate Sch, Microbiol Dept, Bellaterra 08193, Spain
:
IrsiCaixa, Badalona 08916, Spain
Univ Vic Cent Univ Catalonia UV UCC, Fac Med, Ctr Hlth & Social Care Res CESS, Vic 08500, Spain
Pons-Grífols, A:
IrsiCaixa, Badalona 08916, Spain
Univ Autonoma Barcelona, Doctorate Sch, Microbiol Dept, Bellaterra 08193, Spain
Trinité, B:
IrsiCaixa, Badalona 08916, Spain
Tarrés-Freixas, F:
IrsiCaixa, Badalona 08916, Spain
:
IrsiCaixa, Badalona 08916, Spain
Urrea, V:
IrsiCaixa, Badalona 08916, Spain
Barreiro, A:
HIPRA, Amer 17170, Spain
Gonzalez-Tendero, A:
HIPRA, Amer 17170, Spain
Rovira-Rigau, M:
HIPRA, Amer 17170, Spain
Cardona, M:
HIPRA, Amer 17170, Spain
Ferrer, L:
HIPRA, Amer 17170, Spain
:
IrsiCaixa, Badalona 08916, Spain
Univ Vic Cent Univ Catalonia UV UCC, Fac Med, Ctr Hlth & Social Care Res CESS, Vic 08500, Spain
Germans Trias I Pujol Hosp, Infect Dis Dept, Badalona 08916, Spain
Carrillo, J:
IrsiCaixa, Badalona 08916, Spain
:
IrsiCaixa, Badalona 08916, Spain
:
IrsiCaixa, Badalona 08916, Spain
Univ Vic Cent Univ Catalonia UV UCC, Fac Med, Ctr Hlth & Social Care Res CESS, Vic 08500, Spain
Germans Trias i Pujol Res Inst IGTP, Badalona 08916, Spain
ISCIII, CIBERINFEC, Madrid 28029, Spain
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