Development of Dendritic Cell Vaccine Against Measles for Patients Following Hematopoietic Cell Transplantation.

Abstract

Measles virus (MV) remains one of the serious pathogens among patients following hematopoietic cell transplantation (HCT). According to our questionnaires reported in Japan Society for Pediatric Hematology from 170 institutes in 2001, 37 patients from 21 institutes were affected with measles after HCT and 3 out of these patients died. This high mortality rate is mainly due to secondary infection, which developed on the basis of immune suppression induced by MV infection. However, only 29 of 170 institutions performed measles vaccination after HCT. It is speculated that the potential of immune suppression by vaccine strain of MV is one of the major reasons for hesitating vaccination following HCT. MV-producing glycoproteins expressed in MV-infected cells play important roles in the induction of immune suppression. MV-infected DCs express measles glycoprotein complexes consisted of fusion (F) and hemagglutinin (HA) protein. During DC-T cell interaction, the signal transmitted from F-HA complex interferes with Jak/STAT and PI3-k/Akt kinase pathways, and eventually inhibits the survival and proliferation of T cells. Here, we produced a DC-based vaccine against MV by loading DCs with MV-infected autologous DCs. MV in the infected DC was inactivated using ultraviolet-B before loaded. The DC-based vaccine neither expressed HA nor inhibited allogeneic T cell proliferation, while induced the production of interferon (IFN)-gamma by autologous CD4+ and CD8+ naive T cells. Importantly, 19 out of 20 DC-vaccines effectively induced IFN-gamma producing cells in vitro, even when prepared from patients who suffered from acute or chronic GvHD, and were taking immunosuppressives. Surprisingly, IFN-gamma producing cells were induced in all 8 patients who had undergone HCT within a year (2 patients in 1 month, 2 in 2 months, 1 in 6 months, 2 in 7 months, and 1 in 10 months). These findings indicate that our DC-based MV vaccine induces MV-specific immunity even in post-HCT patients without immune suppression, and enable early immunization safely following HCT.