Oral live vaccine strain-induced protective immunity against pulmonary francisella tularensis challenge is mediated by CD4 + T cells and antibodies, including immunoglobulin A

Heather J. Ray, Yu Cong, Ashlesh K. Murthy, Dale M. Selby, Karl E. Klose, Jeffrey R. Barker, M. Neal Guentzel, Bernard P. Arulanandam

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Francisella tularensis is an intracellular gram-negative bacterium and the etiological agent of pulmonary tularemia. Given the high degrees of infectivity in the host and of dissemination of bacteria following respiratory infection, immunization strategies that target mucosal surfaces are critical for the development of effective vaccines against this organism. In this study, we have characterized the efficacy of protective immunity against pneumonic tularemia following oral vaccination with F. tularensis LVS (live vaccine strain). Mice vaccinated orally with LVS displayed colocalization of LVS with intestinal M cells, with subsequent enhanced production of splenic antigen-specific gamma interferon and of systemic and mucosal antibodies, including immunoglobulin A (IgA). LVS-vaccinated BALB/c mice were highly protected against intranasal (i.n.) SCHU S4 challenge and exhibited significantly less bacterial replication in the lungs, liver, and spleen than mockimmunized animals. Depletion of CD4+ T cells significantly abrogated the protective immunity, and mice deficient in B cells or IgA displayed partial protection against SCHU S4 challenge. These results suggest that oral vaccination with LVS induces protective immunity against i.n. challenge with F. tularensis SCHU S4 by a process mediated cooperatively by CD4 + T cells and antibodies, including IgA.

Original languageEnglish (US)
Pages (from-to)444-452
Number of pages9
JournalClinical and Vaccine Immunology
Volume16
Issue number4
DOIs
StatePublished - Apr 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

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