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

Antonella Caivano, Nicole A. Doria-Rose, Benjamin Buelow, Rossella Sartorius, Maria Trovato, Luciana D'Apice, Gonzalo J. Domingo, William F. Sutton, Nancy Haigwood, Piergiuseppe De Berardinis

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    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.

    Original languageEnglish (US)
    Pages (from-to)296-305
    Number of pages10
    JournalVirology
    Volume407
    Issue number2
    DOIs
    StatePublished - Nov 25 2010

    Fingerprint

    Geobacillus stearothermophilus
    Humoral Immunity
    Cellular Immunity
    Virion
    HIV-1
    T-Lymphocytes
    Antibody Formation
    gag Gene Products
    Antibodies
    Pyruvic Acid
    Transgenic Mice
    Immunization
    Oxidoreductases
    Proteins
    Vaccines
    Immunoglobulin G
    Antigens

    Keywords

    • E2 scaffold
    • Gag (p17)
    • HIV
    • Vaccine
    • Virus-like particles

    ASJC Scopus subject areas

    • Virology
    • Medicine(all)

    Cite this

    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. / Caivano, Antonella; Doria-Rose, Nicole A.; Buelow, Benjamin; Sartorius, Rossella; Trovato, Maria; D'Apice, Luciana; Domingo, Gonzalo J.; Sutton, William F.; Haigwood, Nancy; De Berardinis, Piergiuseppe.

    In: Virology, Vol. 407, No. 2, 25.11.2010, p. 296-305.

    Research output: Contribution to journalArticle

    Caivano, Antonella ; Doria-Rose, Nicole A. ; Buelow, Benjamin ; Sartorius, Rossella ; Trovato, Maria ; D'Apice, Luciana ; Domingo, Gonzalo J. ; Sutton, William F. ; Haigwood, Nancy ; De Berardinis, Piergiuseppe. / 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. In: Virology. 2010 ; Vol. 407, No. 2. pp. 296-305.
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