Early and repeated IgG1Fc-pCons chimera vaccinations (GX101) improve the outcome in SLE-prone mice
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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.
KeywordsSLE DNA vaccination Immune tolerance Treg DMARD
This work was supported by a grant from Compagnia di San Paolo, Torino, entitled “Immunoterapia anti-tumorale: analisi d’efficacia dei principali protocolli tradizionali d’immunizzazione e validazione dell’efficacia dell’inibizione dell’interleuchina 10 nel trattamento del melanoma”, and by a grant from Genovax s.r.l. entitled “Analisi fenotipiche e funzionali su linfociti di topi lupus-prone sottoposti a differenti trattamenti vaccinali a scopo tollerogenico”.
Conflict of interest
GX101 has been licensed by the University of Genoa and the University of California, Los Angeles (UCLA), to Genovax s.r.l. Domenico Criscuolo is the President of Genovax; Domenico Barone is the consultant of Genovax for animal studies. Gilberto Filaci, Francesco Indiveri, Daniela Fenoglio, and Giuseppe Balbi are stockholders of Genovax; however, they worked at the project as academics so that they did not receive any payment by Genovax. These authors have no additional financial interests. All the other authors have no conflicting financial interests.
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