Efficient mucosal delivery of the HIV-1 Tat protein using the synthetic lipopeptide MALP-2 as adjuvant.
A major requirement for HIV/AIDS research is the development of a mucosal vaccine that stimulates humoral and cell-mediated immune responses at systemic and mucosal levels, thereby blocking virus replication at the entry port. Thus, a vaccine prototype based on biologically active HIV-1 Tat protein as antigen and the synthetic lipopeptide, macrophage-activating lipopeptide-2 (MALP-2), asa mucosal adjuvant was developed. Intranasal administration to mice stimulated systemic and mucosal anti-Tat antibody responses, and Tat-specific T cell responses, that were more efficient than those observed after i.p. immunization with Tat plus incomplete Freund's adjuvant. Major linear B cell epitopes mapped within aa 1-20 and 46-60, whereas T cell epitopes were identified within aa 36-50 and 56-70. These epitopes have also been described in vaccinated primates and in HIV-1-infected individuals with better prognosis. Analysis of the anti-Tat IgG isotypes in serum, and the cytokine profile of spleen cells indicated that a dominant Th1 helper response was stimulated by Tat plus MALP-2, as opposed to the Th2 response observed with Tat plus incomplete Freund's adjuvant. Tat-specific IFN-gamma-producing cells were significantly increased only in response to Tat plus MALP-2. These data suggest that Malp-2 may represent an optimal mucosal adjuvant for candidate HIV vaccines based on Tat alone or in combination with other HIV antigens.
Borsutzky
Stefan
S
Vaccine Research Group, Division of Microbiology, GBF-German Research Center for Biotechnology, Braunschweig, Germany.
Fiorelli
Valeria
V
Ebensen
Thomas
T
Tripiciano
Antonella
A
Rharbaoui
Faiza
F
Scoglio
Arianna
A
Link
Claudia
C
Nappi
Filomena
F
Morr
Michael
M
Buttó
Stefano
S
Cafaro
Aurelio
A
Mühlradt
Peter F
PF
Ensoli
Barbara
B
Guzmán
Carlos A
CA
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant; D015696:Gene Products, tat / Q000008:administration & dosage / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000097:blood; D015497:HIV-1 / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D055666:Lipopeptides; D008168:Lung / Q000276:immunology; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000276:immunology; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014621:Vagina / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000939:Epitopes; D015696:Gene Products, tat; D015483:HIV Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D055666:Lipopeptides; D008222:Lymphokines; D009842:Oligopeptides; C421254:human immunodeficiency virus type 1 Tat vaccine; D054322:tat Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma; D005620:Freund's Adjuvant; C106335:macrophage stimulatory lipopeptide 2