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 L. Haigwood, Piergiuseppe De Berardinis

Research output: Contribution to journalArticle

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
Pages (from-to)296-305
Number of pages10
JournalVirology
Volume407
Issue number2
DOIs
Publication statusPublished - Nov 25 2010

Keywords

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

ASJC Scopus subject areas

  • Virology
  • Medicine(all)

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