title: HIV-1 Gag p17 presented as virus-like particles on the E2 scaffold from Geobacillus stearothermophilus induces sustained humoral and cellular immune responses in the absence of IFNγ production by CD4+ T cells.
abstract: We have constructed stable virus-like particles displaying the HIV-1 Gag(p17) protein as an N-terminal fusion with an engineered protein domain from the Geobacillus stearothermophilus pyruvate dehydrogenase subunit E2. Mice immunized with the Gag(p17)-E2 60-mer scaffold particles mounted a strong and sustained antibody response. Antibodies directed to Gag(p17) were boosted significantly with additional immunizations, while anti-E2 responses reached a plateau. The isotype of the induced antibodies was biased towards IgG1, and the E2-primed CD4+ T cells did not secrete IFNγ. Using transgenic mouse model systems, we demonstrated that CD8+ T cells primed with E2 particles were able to exert lytic activity and produce IFNγ. These results show that the E2 scaffold represents a powerful vaccine delivery system for whole antigenic proteins or polyepitope engineered proteins, evoking antibody production and antigen specific CTL activity even in the absence of IFNγ-producing CD4+ T cells.
authors.affiliation: Institute of Protein Biochemistry, C.N.R., via P. Castellino 111, 80131 Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Caivano
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Doria-Rose
authors.forename: Benjamin
authors.initials: B
authors.lastname: Buelow
authors.forename: Rossella
authors.initials: R
authors.lastname: Sartorius
authors.forename: Maria
authors.initials: M
authors.lastname: Trovato
authors.forename: Luciana
authors.initials: L
authors.lastname: D'Apice
authors.forename: Gonzalo J
authors.initials: GJ
authors.lastname: Domingo
authors.forename: William F
authors.initials: WF
authors.lastname: Sutton
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Haigwood
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: De Berardinis
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000217:Acyltransferases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors; D001411:Geobacillus stearothermophilus / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015483:HIV Antibodies / Q000097:blood*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014771:Virion / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D016915:AIDS Vaccines; D001426:Bacterial Proteins; D015483:HIV Antibodies; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C473991:p17 gag peptide, human immunodeficiency virus; D007371:Interferon-gamma; D000217:Acyltransferases