Mucosal delivery of the human immunodeficiency virus-1 Tat protein in mice elicits systemic neutralizing antibodies, cytotoxic T lymphocytes and mucosal IgA.
Human immunodeficiency virus (HIV)-1 Tat protein induces protection in non-human primates upon systemic vaccination. In view of the design of mucosal vaccines against HIV-1 we studied the immune response to native Tat (aa 1-86) in mice following intranasal delivery of the protein with two mucosal adjuvants, Escherichia coli heat-labile enterotoxin (LT) and LT-R72, a non-toxic mutant of LT. Immunization with Tat and the two adjuvants induced in BALB/c but not in C57BL/6 mice high and persistent levels of serum IgG and secretory IgA in vaginal and intestinal fluids. Mice sera neutralized Tat and recognized two epitopes mapping in the regions 1-20 and 46-60. Furthermore, their splenocytes proliferated and secreted IFN-gamma and IL-6 in response to Tat. Finally, CTLs were also elicited and they recognized an epitope localized within aa 11-40 of Tat.
Marinaro
Mariarosaria
M
Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Riccomi
Antonella
A
Rappuoli
Rino
R
Pizza
Mariagrazia
M
Fiorelli
Valeria
V
Tripiciano
Antonella
A
Cafaro
Aurelio
A
Ensoli
Barbara
B
De Magistris
Maria Teresa
MT
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D004768:Enterotoxins / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D029968:Escherichia coli Proteins; D005260:Female; D015696:Gene Products, tat / Q000008:administration & dosage / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007422:Intestines / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology*; D014621:Vagina / Q000276:immunology
D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D015696:Gene Products, tat; D015483:HIV Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C027538:heat-labile enterotoxin, E coli