Genetically detoxified mutants of heat-labile enterotoxin from Escherichia coli are effective adjuvants for induction of cytotoxic T-cell responses against HIV-1 gag-p55.
There is an urgent need for prophylactic and therapeutic vaccines against human immunodeficiency virus (HIV). Mucosal immunization strategies have great potential to elicit both mucosal and systemic cellular immunity required to protect against HIV-induced acquired immune deficiency syndrome (AIDS). However, mucosal immunizations with soluble protein antigens generally require adjuvants. In this study, we tested two mutants of the heat-labile enterotoxin (LT) from Escherichia coli, LTK63: with no measurable ADP-ribosyltransferase activity, and LTR72: with residual ADP-ribosyltransferase activity, as mucosal adjuvants for induction of cytotoxic T lymphocyte (CTL) responses to coadministered HIV gag p55 protein. We found that intranasal (i.n.) immunizations with HIV gag p55 protein coadministered with LTK63 or LTR72 induced systemic CTL responses comparable to that obtained following intramuscular (i. m.) immunizations with the same adjuvants. Moreover, oral coadministration of LTR72, but not LTK63, resulted in local as well as systemic p55-specific CTL responses in mesenteric lymph nodes (MLN) and spleens (SP) of the immunized mice. These data have important implications for current efforts to develop a safe vaccine against HIV.
Neidleman
J A
JA
Chiron Corporation, Emeryville, CA, USA.
Vajdy
M
M
Ugozzoli
M
M
Ott
G
G
O'Hagan
D
D
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D018929:Cell Culture Techniques; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D029968:Escherichia coli Proteins; D005260:Female; D015683:Gene Products, gag / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D011498:Protein Precursors / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D015683:Gene Products, gag; D011498:Protein Precursors; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; C027538:heat-labile enterotoxin, E coli