Heat shock protein gp96-Ig vaccine induces antigen specific CD8 T cell response in the placenta

Abstract

Abstract The placenta acts as a barrier against infections, due to multiple unique structural, cellular, and immune properties. The detrimental effects of congenital viruses, including Zika virus (ZIKV), on pregnancy and fetal outcomes occur in part because of impaired placental function and profound pathological changes have been observed infected placentas. Our hypothesis is that induction of appropriate vaccine-induced immune responses in the placenta are key to successful prevention of congenital viruses’ infections in developing fetus. The main goal of our study is to developed novel heat shock protein (HSP) based vaccine approach that will induce antigen-specific responses in the placenta and will lead to the prevention of the pathogen transmission to the fetus. HSP gp96 is a biological adjuvant that activates antigen-presenting cells and simultaneously delivers antigen specific peptides to MHC I for CD8 T cell activation. B6 females were mated with B6 mice and gestation day (GD) 0.5 was determined by the presence of vaginal plug. At GD 5.5, 0.5 million of OT1-gfp cells were injected in the tail vein. Two days after, 2.5 million 3T3-gp96-OVA-Ig or 3T3-gp96-Ig cells were injected subcutaneously (SC). Five days later, pregnant uteri were collected and placental and decidual single cells suspension was obtained. Frequency of OT1-gfp cells was determent by flow cytometry. We found that secreted gp96 vaccine delivered by SC route induces very high frequency of antigen specific CD8 T cells in the placenta (15%) and decidua (10%) without compromising placental or fetal viability. Our findings are highly supportive of development of novel gp96-Ig vaccine as unique systemic and placenta-homing, antigen-specific CD8 CTL vaccine strategy.