title: Early and repeated IgG1Fc-pCons chimera vaccinations (GX101) improve the outcome in SLE-prone mice.
abstract: A previous study showed that a tolerogenic gene vaccine based on a IgG1Fc-pCons chimera (here named GX101) protects NZB/NZW mice from SLE development. The present study was aimed at identifying the most effective schedule of immunization and the possible involvement of CD4(+) Foxp3(+) Treg in the mechanism of action, in view of its eventual translation to the human studies. NZB/NZW mice were vaccinated with B lymphocytes made transgenic by spontaneous transgenesis with a gene coding for a chimeric IgG1Fc-pCons construct. Different schedules of vaccination were set in relation to the timing and number of administrations. Survival, proteinuria levels, and CD4(+) Foxp3(+) Treg frequency were monitored during the full experiments. GX101-treated mice showed delayed disease onset and delayed mortality than controls. GX101 effects were implemented by early as well as repeated vaccine administrations. GX101 vaccination was associated with increased frequencies of CD4(+) CD25(+) Foxp3(+) Treg with respect to controls. This study demonstrates that early and repeated immunizations with GX101 vaccine provide a better outcome than late or single vaccine administration regarding onset/development in SLE-prone mice, acting as a possible disease-modifying approach. Vaccine effects are likely related to CD4(+) Foxp3(+) Treg cell expansion.
authors: Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV n. 7, 16132, Genoa, Italy.
authors: Francesca
authors: F
authors: Ferrera
authors: Daniela
authors: D
authors: Fenoglio
authors: Maurizio
authors: M
authors: Cutolo
authors: Giuseppe
authors: G
authors: Balbi
authors: Alessia
authors: A
authors: Parodi
authors: Florinda
authors: F
authors: Battaglia
authors: Francesca
authors: F
authors: Kalli
authors: Domenico
authors: D
authors: Barone
authors: Francesco
authors: F
authors: Indiveri
authors: Domenico
authors: D
authors: Criscuolo
authors: Gilberto
authors: G
authors: Filaci
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007165:Immunosuppression Therapy; D008180:Lupus Erythematosus, Systemic / Q000473:pathology* / Q000517:prevention & control*; D051379:Mice; D011507:Proteinuria / Q000517:prevention & control; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*