Construction of an unmarked recombinant BCG expressing a pertussis antigen by auxotrophic complementation: Protection against Bordetella pertussis challenge in neonates

Ivan P. Nascimento, Waldely O. Dias, Wagner Quintilio, Tsungda Hsu, William R. Jacobs, Luciana C.C. Leite

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Mycobacterium bovis BCG has long been investigated as a candidate for heterologous antigen presentation. We have previously described an rBCG-Pertussis that confers protection against challenge with Bordetella pertussis in neonate and adult mice. In order to obtain stable expression in vivo, we constructed an unmarked BCG lysine auxotrophic and a complementation vector containing the lysine and the genetically detoxified S1 pertussis toxin genes, both under control of the same promoter. Complemented BCG-Δlysine growth and expression of the pertussis antigen were stable, without the use of an antibiotic marker. Our results show that the complemented rBCG-ΔlysA-S1PT-lysA+(kan-), which is now suitable to be evaluated in clinical trials, maintains similar characteristics of the original rBCG-pNL71S1PT strain, such as the antigen expression level, cellular immune response and protection against the same model challenge in neonatal-immunized mice.

Original languageEnglish (US)
Pages (from-to)7346-7351
Number of pages6
JournalVaccine
Volume27
Issue number52
DOIs
StatePublished - Dec 9 2009

Keywords

  • Auxotroph
  • Complementation
  • Neonates
  • Pertussis
  • Recombinant BCG
  • Vaccine

ASJC Scopus subject areas

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

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