IE1-pp65 recombinant protein from human CMV combined with a nanoparticulate carrier, SMBV, as a potential source for the development of anti-human CMV adoptive immunotherapy.
BACKGROUND
Human cytomegalovirus (HCMV) infection and reactivation following allogeneic bone marrow transplantation is a major source of complications in grafted patients including pneumonitis, graft rejection and even death. Adoptive immunotherapy consisting in transfer of CD4(+) and CD8(+) T cells directed against HCMV has proved its worth. Nevertheless, established procedures have to be improved in terms of safety and waiting period required to obtain specific T cells.


METHODS
As an alternative to infectious virus used in current strategies, we purified a recombinant protein IE1-pp65 resulting from the fusion of the regulatory IE1 and matrix pp65 proteins, both known as the major targets of the overall anti-HCMV T cell response. Based on our previous data demonstrating its use for in vitro stimulation and expansion of anti-HCMV CD4(+) and CD8(+) T cells (Vaz-Santiago et al, 2001, J.Virol, 75:7840-47) from peripheral blood mononuclear cells (PBMC) of seropositive donors, we planned to improve its in vitro immunogenicity through association with a nanoparticulate carrier, SMBV.


RESULTS
We demonstrated that using of SMBV/IE1-pp65 formulation allowed to potentiate in vitro activation of T cells and to expand more CD8(+) T cells than with soluble IE1-pp65, following stimulation of PBMC.


CONCLUSIONS
These data suggest the use of SMBV/IE1-pp65 formulation as a potential source of antigen for efficient T cells expansion in the development of safe anti-HCMV immunotherapy.
Vaz-Santiago
J
J
Biovector Therapeutics, 31676, Labège Cédex, France.
Lulé
J
J
Rohrlich
P
P
Kravtzoff
R
R
Le Roy
E
E
Davignon
J-L
JL
Betbeder
D
D
Davrinche
C
C
D000956:Antigens, Viral / Q000235:genetics; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000628:therapy*; D004337:Drug Carriers; D006801:Humans; D017874:Immediate-Early Proteins / Q000008:administration & dosage / Q000235:genetics*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation; D010750:Phosphoproteins / Q000008:administration & dosage / Q000235:genetics*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014763:Viral Matrix Proteins / Q000008:administration & dosage / Q000235:genetics*; D014764:Viral Proteins
D000956:Antigens, Viral; D004337:Drug Carriers; C088645:IE1 protein, cytomegalovirus; C464970:IE1-pp65 recombinant protein, Human cytomegalovirus; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C065418:cytomegalovirus matrix protein 65kDa