Abstract:
:The recent development of acellular pertussis vaccines has been a significant improvement in the conventional whole-cell diphtheria-pertussis-tetanus toxoid vaccines, but high production costs will limit its widespread use in developing countries. Since Mycobacterium bovis BCG vaccination against tuberculosis is used in most developing countries, a recombinant BCG-pertussis vaccine could be a more viable alternative. We have constructed recombinant BCG (rBCG) strains expressing the genetically detoxified S1 subunit of pertussis toxin 9K/129G (S1PT) in fusion with either the beta-lactamase signal sequence or the whole beta-lactamase protein, under control of the upregulated M. fortuitum beta-lactamase promoter, pBlaF*. Expression levels were higher in the fusion with the whole beta-lactamase protein, and both were localized to the mycobacterial cell wall. The expression vectors were relatively stable in vivo, since at two months 85% of the BCG recovered from the spleens of vaccinated mice maintained kanamycin resistance. Spleen cells from rBCG-S1PT-vaccinated mice showed elevated gamma interferon (IFN-gamma) and low interleukin-4 (IL-4) production, as well as increased proliferation, upon pertussis toxin (PT) stimulation, characterizing a strong antigen-specific Th1-dominant cellular response. The rBCG-S1PT strains induced a low humoral response against PT after 2 months. Mice immunized with rBCG-S1PT strains displayed high-level protection against an intracerebral challenge with live Bordetella pertussis, which correlated with the induction of a PT-specific cellular immune response, reinforcing the importance of cell-mediated immunity in the protection against B. pertussis infection. Our results suggest that rBCG-expressing pertussis antigens could constitute an effective, low-cost combined vaccine against tuberculosis and pertussis.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Nascimento IP,Dias WO,Mazzantini RP,Miyaji EN,Gamberini M,Quintilio W,Gebara VC,Cardoso DF,Ho PL,Raw I,Winter N,Gicquel B,Rappuoli R,Leite LCdoi
10.1128/iai.68.9.4877-4883.2000keywords:
subject
Has Abstractpub_date
2000-09-01 00:00:00pages
4877-83issue
9eissn
0019-9567issn
1098-5522journal_volume
68pub_type
杂志文章abstract::Endocarditis isolates of Enterococcus faecalis produced biofilm significantly more often than nonendocarditis isolates, and 39% of 79 versus 6% of 84 isolates produced strong biofilm (P < 0.0001). esp was not required, but its presence was associated with higher amounts of biofilm (P < 0.001). Mutants disrupted in dlt...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.72.6.3658-3663.2004
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journal_title:Infection and immunity
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doi:10.1128/IAI.60.9.3620-3629.1992
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journal_title:Infection and immunity
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doi:10.1128/IAI.01995-06
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.73.3.1695-1705.2005
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.62.4.1406-1409.1994
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journal_title:Infection and immunity
pub_type: 杂志文章
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journal_title:Infection and immunity
pub_type: 杂志文章
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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doi:10.1128/IAI.62.11.5075-5084.1994
更新日期:1994-11-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.57.2.602-608.1989
更新日期:1989-02-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.60.5.1747-1755.1992
更新日期:1992-05-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.66.11.5107-5112.1998
更新日期:1998-11-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/IAI.00470-08
更新日期:2009-05-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.20.1.130-135.1978
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journal_title:Infection and immunity
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doi:10.1128/IAI.66.10.4788-4796.1998
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doi:10.1128/IAI.15.1.124-131.1977
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.58.5.1360-1368.1990
更新日期:1990-05-01 00:00:00
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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doi:10.1128/IAI.51.1.250-253.1986
更新日期:1986-01-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:2004-09-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:1992-01-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.26.1.1-3.1979
更新日期:1979-10-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:2019-10-18 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.12.4.901-909.1975
更新日期:1975-10-01 00:00:00
abstract::Infection with Mycobacterium avium subsp. paratuberculosis is associated with high levels of morbidity, decreased production, and early culling in dairy cattle. Clinical symptoms of Johne's disease include persistent diarrhea, inappetence, and resultant weight loss due to chronic inflammation of the small intestine. A...
journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:2003-11-01 00:00:00