title: Vaccination with a mutated variant of human Vascular Endothelial Growth Factor (VEGF) blocks VEGF-induced retinal neovascularization in a rabbit experimental model.
abstract: Vascular Endothelial Growth Factor (VEGF) is a key driver of the neovascularization and vascular permeability that leads to the loss of visual acuity of eye diseases like wet age-related macular degeneration, diabetic macular edema, and retinopathy of premature. Among the several anti-VEGF therapies under investigation for the treatment of neovascular eye diseases, our group has developed the vaccine candidate CIGB-247-V that uses a mutated form of human VEGF as antigen. In this work we evaluated if the vaccine could prevent or attenuate VEGF-induced retinal neovascularization in the course of a rabbit eye neovascularization model, based on direct intravitreal injection of human VEGF. Our experimental findings have shown that anti-VEGF IgG antibodies induced by the vaccine were available in the retina blood circulation, and could neutralize in situ the neovascularization effect of VEGF. CIGB-247-V vaccination proved to effectively reduce retinal neovascularization caused by intravitreal VEGF injection. Altogether, these results open the way for human studies of the vaccine in neovascular eye syndromes, and inform on the potential mechanisms involved in its effect.
authors.affiliation: Cancer Immunotherapy Laboratory, Department of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Ave. 31/158 and 190, Cubanacán, Playa, Havana 10600, Cuba. Electronic address: yanelys.morera@cigb.edu.cu.
authors.forename: Yanelys
authors.initials: Y
authors.lastname: Morera
authors.affiliation: Cuban Institute of Ophthalmology "Ramón Pando Ferrer", Ave. 76 # 3104 %31 and 41, Marianao, Havana 10600, Cuba.
authors.forename: Rafael
authors.initials: R
authors.lastname: González
authors.affiliation: Cancer Immunotherapy Laboratory, Department of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Ave. 31/158 and 190, Cubanacán, Playa, Havana 10600, Cuba.
authors.forename: Humberto
authors.initials: H
authors.lastname: Lamdan
authors.affiliation: Cancer Immunotherapy Laboratory, Department of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Ave. 31/158 and 190, Cubanacán, Playa, Havana 10600, Cuba.
authors.forename: Lincidio
authors.initials: L
authors.lastname: Pérez
authors.affiliation: Cuban Institute of Ophthalmology "Ramón Pando Ferrer", Ave. 76 # 3104 %31 and 41, Marianao, Havana 10600, Cuba.
authors.forename: Yorlandis
authors.initials: Y
authors.lastname: González
authors.affiliation: Cuban Institute of Ophthalmology "Ramón Pando Ferrer", Ave. 76 # 3104 %31 and 41, Marianao, Havana 10600, Cuba.
authors.forename: Judith
authors.initials: J
authors.lastname: Agüero
authors.affiliation: Animal Facility, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Ave. 31/158 and 190, Cubanacán, Playa, Havana 10600, Cuba.
authors.forename: Jorge
authors.initials: J
authors.lastname: Castro
authors.affiliation: Animal Facility, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Ave. 31/158 and 190, Cubanacán, Playa, Havana 10600, Cuba.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Romero
authors.affiliation: Cancer Immunotherapy Laboratory, Department of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Ave. 31/158 and 190, Cubanacán, Playa, Havana 10600, Cuba.
authors.forename: Ana Yansy
authors.initials: AY
authors.lastname: Etchegoyen
authors.affiliation: Cancer Immunotherapy Laboratory, Department of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Ave. 31/158 and 190, Cubanacán, Playa, Havana 10600, Cuba.
authors.forename: Marta
authors.initials: M
authors.lastname: Ayala
authors.affiliation: Cancer Immunotherapy Laboratory, Department of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Ave. 31/158 and 190, Cubanacán, Playa, Havana 10600, Cuba.
authors.forename: Jorge V
authors.initials: JV
authors.lastname: Gavilondo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005451:Fluorescein Angiography; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D058449:Intravitreal Injections; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control*; D012171:Retinal Vessels / Q000473:pathology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology* / Q000633:toxicity; D014822:Vitreous Body / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D014614:Vaccines, Synthetic; D042461:Vascular Endothelial Growth Factor A
keywords: CIGB-247-V; VEGF; angiogenesis; retinal neovascularization; vaccine