Intranasal administration of a synthetic lipopeptide without adjuvant induces systemic immune responses.
Parenteral injection of a lipopeptide containing a human leucocyte antigen (HLA)-A*0201-restricted cytotoxic T-lymphocyte (CTL) epitope from the human cytomegalovirus (HCMV) immunodominant matrix protein pp65 efficiently induces systemic CTL responses in HLA-A*0201 transgenic mice. In this study, we demonstrate that intranasal (i.n.) administration of this lipopeptide, covalently linked to a universal T helper (Th) epitope (PADRE), also induces potent systemic CTL responses. Immune responses were substantially reduced when the unlipidated peptide analogue was used (P<0.01). The induced CTL were CD8+, major histocompatibility complex (MHC) class I-restricted and CMV specific. Moreover, i.n. administration of this lipidated peptide elicited both systemic and local mucosal CD4+ T-cell proliferative responses, as well as antigen-specific delayed type hypersensitivity (DTH) immune responses. In contrast, mice receiving the unlipidated peptide analogue developed substantially reduced Th or DTH responses (P<0.05). These results highlight the usefulness and potential of lipopeptides delivered via mucosal routes as painless, safe, and non-invasive vaccines.
BenMohamed
Lbachir
L
Laboratory of Vaccine Research, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
Krishnan
Radhika
R
Auge
Catherine
C
Primus
James F
JF
Diamond
Don J
DJ
D000281:Administration, Intranasal; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D022482:Cytomegalovirus Vaccines / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*
D000956:Antigens, Viral; D022482:Cytomegalovirus Vaccines; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D017780:Malaria Vaccines; C401223:PADRE 45; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa