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

doi:10.1016/j.vaccine.2009.09.043

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

Microbiology & Immunology

Research output: Contribution to journal › Article › peer-review

26 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 language	English (US)
Pages (from-to)	7346-7351
Number of pages	6
Journal	Vaccine
Volume	27
Issue number	52
DOIs	https://doi.org/10.1016/j.vaccine.2009.09.043
State	Published - Dec 9 2009

Keywords

Auxotroph
Complementation
Neonates
Pertussis
Recombinant BCG
Vaccine

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.vaccine.2009.09.043

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@article{35798c4fdeb54a5385d31d518fa0449a,

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

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.",

keywords = "Auxotroph, Complementation, Neonates, Pertussis, Recombinant BCG, Vaccine",

author = "Nascimento, {Ivan P.} and Dias, {Waldely O.} and Wagner Quintilio and Tsungda Hsu and Jacobs, {William R.} and Leite, {Luciana C.C.}",

note = "Funding Information: The experiments reported herein were performed according to principles set forth in the Guide for Care and Use of Laboratory Animals and approved by the Committee for Ethics in the Use of the Animals of Instituto Butantan. This work was supported by the Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo-FAPESP (Ref. No. 96/11539-0), Conselho Nacional de Desenvolvimento Cient{\'i}fico e Tecnol{\'o}gico (CNPq) and Funda{\c c}{\~a}o Butantan, S{\~a}o Paulo, SP, Brazil . I.P. Nascimento was supported by a FAPESP Post-Doctoral fellowship (Ref. No. 02/01748-4). We thank Dr. Michelle Darrieux for assistance in the preparation of the manuscript.",

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language = "English (US)",

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T1 - Construction of an unmarked recombinant BCG expressing a pertussis antigen by auxotrophic complementation

T2 - Protection against Bordetella pertussis challenge in neonates

AU - Nascimento, Ivan P.

AU - Dias, Waldely O.

AU - Quintilio, Wagner

AU - Hsu, Tsungda

AU - Jacobs, William R.

AU - Leite, Luciana C.C.

N1 - Funding Information: The experiments reported herein were performed according to principles set forth in the Guide for Care and Use of Laboratory Animals and approved by the Committee for Ethics in the Use of the Animals of Instituto Butantan. This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP (Ref. No. 96/11539-0), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação Butantan, São Paulo, SP, Brazil . I.P. Nascimento was supported by a FAPESP Post-Doctoral fellowship (Ref. No. 02/01748-4). We thank Dr. Michelle Darrieux for assistance in the preparation of the manuscript.

PY - 2009/12/9

Y1 - 2009/12/9

N2 - 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.

AB - 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.

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KW - Complementation

KW - Neonates

KW - Pertussis

KW - Recombinant BCG

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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