An anthrax subunit vaccine candidate based on protective regions of Bacillus anthracis protective antigen and lethal factor

Les W Baillie, Theresa B Huwar, Stephen Moore, Gabriela Mellado-Sanchez, Liliana Rodriguez, Brendan N Neeson, Helen C Flick-Smith, Dominic C Jenner, Helen S Atkins, Rebecca J Ingram, Danny M Altmann, James P Nataro, Marcela F Pasetti

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Studies have confirmed the key role of Bacillus anthracis protective antigen (PA) in the US and UK human anthrax vaccines. However, given the tripartite nature of the toxin, other components, including lethal factor (LF), are also likely to contribute to protection. We examined the antibody and T cell responses to PA and LF in human volunteers immunized with the UK anthrax vaccine (AVP). Individual LF domains were assessed for immunogenicity in mice when given alone or with PA. Based on the results obtained, a novel fusion protein comprising D1 of LF and the host cell-binding domain of PA (D4) was assessed for protective efficacy. Murine protection studies demonstrated that both full-length LF and D1 of LF conferred complete protection against a lethal intraperitoneal challenge with B. anthracis STI spores. Subsequent studies with the LFD1-PAD4 fusion protein showed a similar level of protection. LF is immunogenic in humans and is likely to contribute to the protection stimulated by AVP. A single vaccine comprising protective regions from LF and PA would simplify production and confer a broader spectrum of protection than that seen with PA alone.
Original languageEnglish
Pages (from-to)6740-8
Number of pages9
JournalVaccine
Volume28
Issue number41
DOIs
Publication statusPublished - Sep 2010

ASJC Scopus subject areas

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

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