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

Author(s)

Nascimento, Ivan P. ^[1] ; Dias, Waldely O. ^[1] ; Quintilio, Wagner ^[2] ; Hsu, Tsungda ^[3] ; Jacobs, Jr., William R. ^{[4, 3]} ; Leite, Luciana C. C. ^[1]

Affiliation

^[1] Inst Butantan, Ctr Biotecnol, BR-05503900 Sao Paulo - Brazil

^[2] Inst Butantan, Div Controle Qualidade, BR-05503900 Sao Paulo - Brazil

^[3] Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10461 - USA

^[4] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 - USA

• Document type: Journal article
• Source: Vaccine; v. 27, n. 52, p. 7346-7351, DEC 9 2009.
• Web of Science Citations: 17

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-Delta lysine growth and expression of the pertussis antigen were stable, without the use of an antibiotic marker. Our results show that the complemented rBCG-Delta lysA-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. (C) 2009 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 96/11539-0 - Development of a recombinant BCG vaccine - DPT
• Grantee: Luciana Cezar de Cerqueira Leite
• Support Opportunities: Regular Research Grants