Induction of SIV capsid-specific CTL and mucosal sIgA in mice immunized with a recombinant S. typhimurium aro A mutant

Peter J. Valentine, Krista Meyer, Martin Muy Rivera, Craig Lipps, David Pauza, Richard Maziarz, Magdalene So, Fred Heffron

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

We have developed a new expression system based on the E. coli groEL promoter. The suicide vector constructed (called APC vector) allows simultaneous attenuation of a Salmonella strain by disruption of the coding sequence for aroA and stable integration of a gene into the bacterial chromosome. High-level expression of antigen is achieved after Salmonella is taken up by macrophages, a major antigen processing cell of the host. The chloramphenicol acetyltransferase (CAT) and the simian immunodeficiency virus capsid (p27gag) genes were cloned downstream of the groEL promoter and expressed within S. typhimurium. By measuring CAT activity, we showed that the groEL promoter was up-regulated during infection of the J774 macrophage line. The immune response to SIV capsid was assessed in Balb/c mice given one oral dose of vaccine. A local mucosal secretory IgA response against SIV capsid was detected but no systemic antibody response to the same antigen. A systemic CTL response was detected as early as 28 days to as late as 70 days post-immunization. CTL activity was MHC restricted (H-2d) and was mediated by CD3+, CD8+, CD4- T-lymphocytes. These results indicate that with only one oral dose of recombinant Salmonella using the APC vector, a systemic CTL response and a mucosal secretory response against the SIV capsid antigen are elicited in a mouse model.

Original languageEnglish (US)
Pages (from-to)138-146
Number of pages9
JournalVaccine
Volume14
Issue number2
DOIs
StatePublished - Feb 1996

Fingerprint

capsid
Capsid
Salmonella
chloramphenicol acetyltransferase
antigens
mutants
Chloramphenicol O-Acetyltransferase
promoter regions
mice
Antigens
mouth
macrophages
Macrophages
Bacterial Chromosomes
Simian immunodeficiency virus
Secretory Immunoglobulin A
Simian Immunodeficiency Virus
suicide
Antigen Presentation
dosage

Keywords

  • Cytotoxic T-lymphocyte
  • groEL promoter
  • Salmonella
  • Vaccine

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

Cite this

Induction of SIV capsid-specific CTL and mucosal sIgA in mice immunized with a recombinant S. typhimurium aro A mutant. / Valentine, Peter J.; Meyer, Krista; Rivera, Martin Muy; Lipps, Craig; Pauza, David; Maziarz, Richard; So, Magdalene; Heffron, Fred.

In: Vaccine, Vol. 14, No. 2, 02.1996, p. 138-146.

Research output: Contribution to journalArticle

Valentine, Peter J. ; Meyer, Krista ; Rivera, Martin Muy ; Lipps, Craig ; Pauza, David ; Maziarz, Richard ; So, Magdalene ; Heffron, Fred. / Induction of SIV capsid-specific CTL and mucosal sIgA in mice immunized with a recombinant S. typhimurium aro A mutant. In: Vaccine. 1996 ; Vol. 14, No. 2. pp. 138-146.
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