Characterization of immune responses elicited in mice by intranasal co-immunization with HIV-1 Tat, gp140 DeltaV2Env and/or SIV Gag proteins and the nontoxicogenic heat-labile Escherichia coli enterotoxin.
The development of a vaccine against HIV/AIDS capable of inducing broad humoral and cellular responses at both systemic and mucosal sites, able to stop or reduce viral infection at the portal of entry, represents the only realistic way to control the infection caused by HIV world-wide. The promising results obtained with the HIV-1 Tat-based vaccines in preclinical and clinical settings, the evidence that a broad immunity against HIV correlates with reduced viral load or virus control, as well as the availability of novel gp140 V2-loop deleted HIV-1 Env (DeltaV2Env) immunogens capable of inducing cross-reactive neutralizing antibodies, have led to the design of new vaccine strategies based on the combination of non-structural and structural proteins. In this study, we demonstrate that immunization with a biologically active HIV-1 Tat protein in combination with the oligomeric HIV-1 gp140 DeltaV2Env and/or SIV Gag proteins, delivered intranasally with the detoxified LTK63 mucosal adjuvant, whose safety has been recently shown in humans, elicits long-lasting local and systemic antibody and cellular immune responses against the co-administered antigens in a fashion similar to immune responses induced by vaccination with Tat, DeltaV2Env and Gag proteins alone. The results indicate lack of antigen interference implying that HIV-1 Tat is an optimal co-antigen for combined vaccine strategies employing DeltaV2Env and/or Gag proteins.
Caputo
Antonella
A
Department of Histology, Microbiology and Medical Biotechnology, University of Padova, Via A. Gabelli 63, 35122 Padova, Italy. antonella.caputo@unipd.it
Brocca-Cofano
Egidio
E
Castaldello
Arianna
A
Voltan
Rebecca
R
Gavioli
Riccardo
R
Srivastava
Indresh K
IK
Barnett
Susan W
SW
Cafaro
Aurelio
A
Ensoli
Barbara
B
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology*; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D015683:Gene Products, gag / Q000276:immunology*; D015696:Gene Products, tat / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D051379:Mice; D008807:Mice, Inbred BALB C; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C033904:GP 140; D015683:Gene Products, gag; D015696:Gene Products, tat; D006023:Glycoproteins; D015483:HIV Antibodies; C421254:human immunodeficiency virus type 1 Tat vaccine; C027538:heat-labile enterotoxin, E coli