ABSTRACT
Opportunistic infection remains the principal cause of mortality in allogeneic stem cell transplant recipients with active extensive chronic graft-versus-host disease. Human cytomegalovirus (HCMV) represents an important cause of disease in this setting and the toxicity of protracted and recurrent antiviral treatment together with eventual drug resistance represents a significant limitation to therapy. Although the expansion and adoptive transfer of HCMV-specific T cells from the healthy original donor can be an effective strategy to control viral replication, this is not possible when donors are seronegative or are subsequently inaccessible. Here we demonstrate for the first time, the successful expansion of HCMV-specific T cells from a seropositive transplant recipient of a seronegative graft with active HCMV disease and the long-term reconstitution of protective antiviral immunity following their adoptive transfer back into the patient.
Subject(s)
Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/therapy , Cytomegalovirus/immunology , Immunotherapy, Adoptive/methods , Stem Cell Transplantation/adverse effects , T-Lymphocytes/immunology , T-Lymphocytes/virology , Adult , Amino Acid Sequence , Antigens, Viral/administration & dosage , Antigens, Viral/genetics , Base Sequence , Cytomegalovirus/genetics , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/etiology , DNA Primers/genetics , Humans , Male , Polymerase Chain Reaction , Transplantation, Homologous , Viral Load , Viral Proteins/administration & dosage , Viral Proteins/genetics , Viral Proteins/immunologyABSTRACT
A mouse model of Helicobacter pylori infection was used to evaluate the vaccine antigen potential of the citrate synthase homologue protein purified from the H. pylori NCTC 11637 strain. Mice were immunised with the protein by intra-Peyer's patch immunisation. This route gives maximal intestinal immunisation and was used to screen oral vaccine candidate antigens without the added complication of simultaneously testing oral delivery systems. Two weeks post-immunisation mice were infected with Sydney strain H. pylori and 4 weeks after infection the mice were killed and the level of H. pylori infection in the stomach determined. Pre-immunisation with the 50/52-kDa protein led to a 84-91% reduction in H. pylori infection compared to unimmunised controls.