Preclinical studies on immunogenicity of the HIV-1 p17-based synthetic peptide AT20-KLH.
Several studies have suggested that HIV-1 p17 matrix protein may play an important role in AIDS pathogenesis, since anti-p17 antibodies represent a serological marker of disease progression during HIV-1 infection both in adults and children. Moreover, it has been recently reported that the viral protein is capable of significantly increasing the proliferation of preactivated T lymphocytes and the release of proinflammatory cytokines. Recombinant HIV-1 p17 also has induced an increased rate of HIV-1 replication in vitro. All p17 biological activities are exerted after its binding to a specific cellular receptor expressed on activated T lymphocytes. The functional p17 epitope involved in receptor binding was found to be located at the NH(2)-terminal region of the viral protein. Immunization of C57BL/6 mice with a 20 amino acid synthetic peptide representative of the HIV-1 p17 functional region (AT20) coupled to the carrier protein keyhole limpet hemocyanin (KLH) and given in Freund's incomplete adjuvant, resulted in the development of p17-neutralizing antibodies capable of blocking p17/p17 receptor interaction, and consequently, all biological activities of the viral protein. Moreover, it was possible to skew the humoral response induced by priming mice with AT20-KLH toward cell-mediated immune responses, boosting animals with p17. Our findings may provide a new strategy to develop a synthetic AIDS vaccine based on a potentially effective and safe subunit vaccine against the HIV-1 cytokine-like matrix protein p17. Preclinical immunogenicity data for AT20-KLH provide the basis for evaluation of the peptide-based vaccine, alone and in combination with p17 or p17 DNA vaccines, in Phase I clinical trials.
Fiorentini
Simona
S
Department of Experimental and Applied Medicine, University of Brescia Medical School, Brescia, Italy. sfiorent@med.unibs.it
Marini
Elena
E
Bozzo
Luisa
L
Trainini
Laura
L
Saadoune
Lamiaa
L
Avolio
Manuela
M
Pontillo
Angela
A
Bonfanti
Carlo
C
Sarmientos
Paolo
P
Caruso
Arnaldo
A
D016915:AIDS Vaccines / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D015683:Gene Products, gag / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis; D015488:HIV Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015683:Gene Products, gag; D015483:HIV Antibodies; D015488:HIV Antigens; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1