CD1d-dependent B-cell help by NK-like T cells leads to enhanced and sustained production of Bacillus anthracis lethal toxin-neutralizing antibodies

T. Scott Devera, Lindsay M. Aye, Gillian A. Lang, Sunil Joshi, Jimmy D. Ballard, Mark L. Lang

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The current Bacillus anthracis vaccine consists largely of protective antigen (PA), the protein of anthrax toxin that mediates entry of edema factor (EF) or lethal factor (LF) into cells. PA induces protective antibody (Ab)-mediated immunity against Bacillus anthracis but has limited efficacy and duration. We previously demonstrated that activation of CD1d-restricted natural killer-like T cells (NKT) with a CD1d-binding glycolipid led to enhanced Ab titers specific for foreign antigen (Ag). We therefore tested the hypothesis that activation of NKT cells with the CD1d ligand (α-galactosylceramide [α-GC]) at the time of immunization improves PA-specific Ab responses. We observed that α-GC enhanced PA-specific Ab titers in C57BL/6 mice. In CD1d-/- mice deficient in type I and type II NKT cells the anti-PA Ab response was diminished. In Jα281-/- mice expressing CD1d but lacking type I α-GC-reactive NKT cells, α-GC did not enhance the Ab response. In vitro neutralization assays were performed and showed that the Ab titers correlated with protection of macrophages against anthrax lethal toxin (LT). The neutralization capacity of the Ab was further tested in lethal challenge studies, which revealed that NKT activation leads to enhanced in vivo protection against LT. Anti-PA Ab titers, neutralization, and protection were then measured over a period of several months, and this revealed that NKT activation leads to a sustained protective Ab response. These results suggest that NKT-activating CD1d ligands could be exploited for the development of improved vaccines for Bacillus anthracis that increase not only neutralizing Ab titers but also the duration of the protection afforded by Ab.

Original languageEnglish (US)
Pages (from-to)1610-1617
Number of pages8
JournalInfection and Immunity
Volume78
Issue number4
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

Fingerprint

Natural Killer T-Cells
Neutralizing Antibodies
B-Lymphocytes
T-Lymphocytes
Antigens
Antibodies
Bacillus anthracis
Antibody Formation
Vaccines
Galactosylceramides
Ligands
Glycolipids
anthrax toxin
Inbred C57BL Mouse
Immunity
Immunization
Macrophages

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

CD1d-dependent B-cell help by NK-like T cells leads to enhanced and sustained production of Bacillus anthracis lethal toxin-neutralizing antibodies. / Devera, T. Scott; Aye, Lindsay M.; Lang, Gillian A.; Joshi, Sunil; Ballard, Jimmy D.; Lang, Mark L.

In: Infection and Immunity, Vol. 78, No. 4, 01.04.2010, p. 1610-1617.

Research output: Contribution to journalArticle

Devera, T. Scott ; Aye, Lindsay M. ; Lang, Gillian A. ; Joshi, Sunil ; Ballard, Jimmy D. ; Lang, Mark L. / CD1d-dependent B-cell help by NK-like T cells leads to enhanced and sustained production of Bacillus anthracis lethal toxin-neutralizing antibodies. In: Infection and Immunity. 2010 ; Vol. 78, No. 4. pp. 1610-1617.
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