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IFN-I blockade improves the immunogenicity of viral vector vaccines
Ist Teil von
The Journal of immunology (1950), 2019-05, Vol.202 (1_Supplement), p.75-75.8
Erscheinungsjahr
2019
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ）
Beschreibungen/Notizen
Abstract
Type I interferons (IFN-I) are critical for antiviral immunity. Studies in the lymphocytic choriomeningitis virus (LCMV) model show that IFN-I signaling improves the control of acute infection, but IFN-I signaling can be immunosuppressive and impair the control of chronic infection. The role of IFN-I after vaccination, however, remains understudied. Vaccination is biologically distinct from natural infection, as immune responses with the former are elicited after in situ challenge with a low dose of an attenuated pathogen, resulting in a benign localized infection that induces immunological memory. To evaluate the role of IFN-I in this setting, we immunized C57BL/6 mice intramuscularly with LCMV-based vaccines expressing model antigens, including SIV Gag, co-administered with IFN-I receptor blocking antibodies. IFN-I blockade resulted in significant improvement of CD8 T cell and B cell responses. Furthermore, IFN-I blockade also improved the immunogenicity of other viral vectors, including rhabdovirus- and poxvirus-based vectors. Improvement of vaccine-elicited immunity was also observed in BALB/c mice using alternative immunization routes. Importantly, transient IFN-I blockade did not affect vaccine clearance, but it abrogated the influx of T regulatory cells (Tregs) to the site of immunization. Our data suggest a model in which IFN-I recruits Tregs to the site of immunization, resulting in in situ regulation of vaccine-induced immunity. Altogether, we show in multiple viral vector regimens, different MHC backgrounds, and different routes, that localized IFN-I modulation improves vaccine-induced immunity. Our findings may be important to develop more potent viral vector vaccines against infectious diseases.