A Combination of Recombinant Mycobacterium bovis BCG Strains Expressing Pneumococcal Proteins Induces Cellular and Humoral Immune Responses and Protects against Pneumococcal Colonization and Sepsis.

Goulart, C; Rodriguez, D; Kanno, AI; Converso, TR; Lu, Y-J; Malley, R; Leite, LCC

A Combination of Recombinant Mycobacterium bovis BCG Strains Expressing Pneumococcal Proteins Induces Cellular and Humoral Immune Responses and Protects against Pneumococcal Colonization and Sepsis.

Goulart, C

Rodriguez, D Kanno, AI Converso, TR Lu, Y-J Malley, R Leite, LCC

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Publisher:: AMER SOC MICROBIOLOGY
Publication Type:: Journal Article
Citation:: Clin Vaccine Immunol, 2017, 24, (10)
Issue Date:: 2017-10

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Field	Value	Language
dc.contributor.author	Goulart, C https://orcid.org/0000-0003-2981-1934
dc.contributor.author	Rodriguez, D
dc.contributor.author	Kanno, AI
dc.contributor.author	Converso, TR
dc.contributor.author	Lu, Y-J
dc.contributor.author	Malley, R
dc.contributor.author	Leite, LCC
dc.date.accessioned	2022-03-22T23:55:07Z
dc.date.available	2017-07-28
dc.date.available	2022-03-22T23:55:07Z
dc.date.issued	2017-10
dc.identifier.citation	Clin Vaccine Immunol, 2017, 24, (10)
dc.identifier.issn	1556-6811
dc.identifier.issn	1556-679X
dc.identifier.uri	http://hdl.handle.net/10453/155471
dc.description.abstract	Pneumococcal diseases remain a substantial cause of mortality in young children in developing countries. The development of potentially serotype-transcending vaccines has been extensively studied; ideally, such a vaccine should include antigens that are able to induce protection against colonization (likely mediated by interleukin-17A [IL-17A]) and invasive disease (likely mediated by antibody). The use of strong adjuvants or alternative delivery systems that are able to improve the immunological response of recombinant proteins has been proposed but poses potential safety and practical concerns in children. We have previously constructed a recombinant Mycobacterium bovis BCG strain expressing a pneumococcal surface protein A (PspA)-PdT fusion protein (rBCG PspA-PdT) that was able to induce an effective immune response and protection against sepsis in a prime-boost strategy. Here, we constructed two new rBCG strains expressing the pneumococcal proteins SP 0148 and SP 2108, which confer IL-17A-dependent protection against pneumococcal colonization in mouse models. Immunization of mice with rBCG 0148 or rBCG 2108 in a prime-boost strategy induced IL-17A and gamma interferon (IFN-γ) production. The combination of these rBCG strains with rBCG PspA-PdT (rBCG Mix), followed by a booster dose of the combined recombinant proteins (rMix) induced an IL-17A response against SP 0148 and SP 2108 and a humoral response characterized by increased levels of IgG2c against PspA and functional antibodies against pneumolysin. Furthermore, immunization with the rBCG Mix prime/rMix booster (rBCG Mix/rMix) provides protection against pneumococcal colonization and sepsis. These results suggest the use of combined rBCG strains as a potentially serotype-transcending pneumococcal vaccine in a prime-boost strategy, which could provide protection against pneumococcal colonization and sepsis.
dc.format	Electronic-Print
dc.language	eng
dc.publisher	AMER SOC MICROBIOLOGY
dc.relation.ispartof	Clin Vaccine Immunol
dc.relation.isbasedon	10.1128/CVI.00133-17
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1107 Immunology
dc.subject.classification	Immunology
dc.subject.classification	Microbiology
dc.subject.mesh	Animals
dc.subject.mesh	Antibodies, Bacterial
dc.subject.mesh	Antigens, Bacterial
dc.subject.mesh	BCG Vaccine
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Female
dc.subject.mesh	Immunity, Cellular
dc.subject.mesh	Immunity, Humoral
dc.subject.mesh	Immunization
dc.subject.mesh	Immunization, Secondary
dc.subject.mesh	Immunoglobulin G
dc.subject.mesh	Interferon-gamma
dc.subject.mesh	Interleukin-17
dc.subject.mesh	Mice
dc.subject.mesh	Mycobacterium bovis
dc.subject.mesh	Pneumococcal Infections
dc.subject.mesh	Pneumococcal Vaccines
dc.subject.mesh	Sepsis
dc.subject.mesh	Streptococcus pneumoniae
dc.subject.mesh	Vaccines, Synthetic
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Mycobacterium bovis
dc.subject.mesh	Streptococcus pneumoniae
dc.subject.mesh	Pneumococcal Infections
dc.subject.mesh	Sepsis
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Immunoglobulin G
dc.subject.mesh	Vaccines, Synthetic
dc.subject.mesh	Interleukin-17
dc.subject.mesh	Pneumococcal Vaccines
dc.subject.mesh	BCG Vaccine
dc.subject.mesh	Antibodies, Bacterial
dc.subject.mesh	Antigens, Bacterial
dc.subject.mesh	Immunization
dc.subject.mesh	Immunization, Secondary
dc.subject.mesh	Immunity, Cellular
dc.subject.mesh	Female
dc.subject.mesh	Interferon-gamma
dc.subject.mesh	Immunity, Humoral
dc.title	A Combination of Recombinant Mycobacterium bovis BCG Strains Expressing Pneumococcal Proteins Induces Cellular and Humoral Immune Responses and Protects against Pneumococcal Colonization and Sepsis.
dc.type	Journal Article
utslib.citation.volume	24
utslib.location.activity	United States
utslib.for	1107 Immunology
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.date.updated	2022-03-22T23:55:00Z
pubs.issue	10
pubs.publication-status	Published online
pubs.volume	24
utslib.citation.issue	10

Abstract:

Pneumococcal diseases remain a substantial cause of mortality in young children in developing countries. The development of potentially serotype-transcending vaccines has been extensively studied; ideally, such a vaccine should include antigens that are able to induce protection against colonization (likely mediated by interleukin-17A [IL-17A]) and invasive disease (likely mediated by antibody). The use of strong adjuvants or alternative delivery systems that are able to improve the immunological response of recombinant proteins has been proposed but poses potential safety and practical concerns in children. We have previously constructed a recombinant Mycobacterium bovis BCG strain expressing a pneumococcal surface protein A (PspA)-PdT fusion protein (rBCG PspA-PdT) that was able to induce an effective immune response and protection against sepsis in a prime-boost strategy. Here, we constructed two new rBCG strains expressing the pneumococcal proteins SP 0148 and SP 2108, which confer IL-17A-dependent protection against pneumococcal colonization in mouse models. Immunization of mice with rBCG 0148 or rBCG 2108 in a prime-boost strategy induced IL-17A and gamma interferon (IFN-γ) production. The combination of these rBCG strains with rBCG PspA-PdT (rBCG Mix), followed by a booster dose of the combined recombinant proteins (rMix) induced an IL-17A response against SP 0148 and SP 2108 and a humoral response characterized by increased levels of IgG2c against PspA and functional antibodies against pneumolysin. Furthermore, immunization with the rBCG Mix prime/rMix booster (rBCG Mix/rMix) provides protection against pneumococcal colonization and sepsis. These results suggest the use of combined rBCG strains as a potentially serotype-transcending pneumococcal vaccine in a prime-boost strategy, which could provide protection against pneumococcal colonization and sepsis.

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http://hdl.handle.net/10453/155471