en
Scientific article
Open access
English

Priming with a recombinant pantothenate auxotroph of Mycobacterium bovis BCG and boosting with MVA elicits HIV-1 Gag specific CD8+ T cells

Published inPloS one, vol. 7, no. 3, e32769
Publication date2012
Abstract

A safe and effective HIV vaccine is required to significantly reduce the number of people becoming infected with HIV each year. In this study wild type Mycobacterium bovis BCG Pasteur and an attenuated pantothenate auxotroph strain (BCGΔpanCD) that is safe in SCID mice, have been compared as vaccine vectors for HIV-1 subtype C Gag. Genetically stable vaccines BCG[pHS400] (BCG-Gag) and BCGΔpanCD[pHS400] (BCGpan-Gag) were generated using the Pasteur strain of BCG, and a panothenate auxotroph of Pasteur respectively. Stability was achieved by the use of a codon optimised gag gene and deletion of the hsp60-lysA promoter-gene cassette from the episomal vector pCB119. In this vector expression of gag is driven by the mtrA promoter and the Gag protein is fused to the Mycobacterium tuberculosis 19 kDa signal sequence. Both BCG-Gag and BCGpan-Gag primed the immune system of BALB/c mice for a boost with a recombinant modified vaccinia virus Ankara expressing Gag (MVA-Gag). After the boost high frequencies of predominantly Gag-specific CD8(+) T cells were detected when BCGpan-Gag was the prime in contrast to induction of predominantly Gag-specific CD4(+) T cells when priming with BCG-Gag. The differing Gag-specific T-cell phenotype elicited by the prime-boost regimens may be related to the reduced inflammation observed with the pantothenate auxotroph strain compared to the parent strain. These features make BCGpan-Gag a more desirable HIV vaccine candidate than BCG-Gag. Although no Gag-specific cells could be detected after vaccination of BALB/c mice with either recombinant BCG vaccine alone, BCGpan-Gag protected mice against a surrogate vaccinia virus challenge.

Keywords
  • AIDS Vaccines/administration & dosage/genetics/immunology
  • Animals
  • BCG Vaccine/administration & dosage/genetics/immunology
  • CD8-Positive T-Lymphocytes/immunology/metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Gene Products, gag/genetics/immunology
  • HIV Infections/immunology/metabolism/prevention & control
  • HIV-1/genetics/immunology
  • Immunization, Secondary/methods
  • Interferon-gamma/immunology/metabolism
  • Interleukin-6/immunology/metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Mycobacterium bovis/genetics/immunology/metabolism
  • Pantothenic Acid/metabolism
  • Spleen/cytology/immunology/metabolism
  • Tumor Necrosis Factor-alpha/immunology/metabolism
  • Vaccination/methods
  • Vaccinia virus/genetics
Funding
  • Swiss National Science Foundation - 3200A0-118196
Citation (ISO format)
CHAPMAN, Rosamund et al. Priming with a recombinant pantothenate auxotroph of Mycobacterium bovis BCG and boosting with MVA elicits HIV-1 Gag specific CD8+ T cells. In: PloS one, 2012, vol. 7, n° 3, p. e32769. doi: 10.1371/journal.pone.0032769
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal1932-6203
578views
304downloads

Technical informations

Creation11/07/2013 4:54:00 PM
First validation11/07/2013 4:54:00 PM
Update time03/14/2023 8:44:21 PM
Status update03/14/2023 8:44:21 PM
Last indexation02/12/2024 11:18:13 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack