Protection of macaques against Mycobacterium tuberculosis infection by a subunit vaccine based on a fusion protein of antigen 85B and ESAT-6

Langermans, Jan A. M.; Doherty, T. Mark; Vervenne, Richard A. W.; Laan, Tridia van der; Lyashchenko, Konstantin P.; Greenwald, Rena; Agger, Else Marie; Aagaard, Claus; Weiler, H.; Soolingen, Dick van; Dalemans, Wilfried; Thomas, Alan W.; Andersen, Peter

doi:10.1016/j.vaccine.2004.11.051

Cited by 221 publications

(138 citation statements)

References 38 publications

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“…While examinations of newly developed attenuated virulent MTB and recombinant BCG strains have shown comparable efficacy with the current BCG vaccine, both involve use of live bacteria, with no comparative history of clinical safety [42][43][44][45][46]. The current BCG vaccine is the most widely administered vaccine in the world, and has a long established history of known benefits and risks [47].…”

Section: Discussionmentioning

confidence: 99%

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Hwang¹,

Kruzel

Actor³

2009

Biochimie

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The current vaccine for tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an attenuated strain of Mycobacterium bovis bacillus Calmette-Guerin (BCG). BCG has proven to be effective in children, however, efficacy wanes in adulthood. Lactoferrin, a natural protein with immunomodulatory properties, is a potential adjuvant candidate to enhance efficacy of BCG. These studies define bovine lactoferrin as an enhancer of the BCG vaccine, functioning in part by modulating macrophage ability to present antigen and stimulate T-cells. BCG-infected bone marrow derived macrophages (BMMs) cultured with bovine lactoferrin increased the number of MHC II + expressing cells. Addition of IFN-γ and lactoferrin to BCG-infected BMMs enhanced MHC II expressiona dna increased the ratio of CD86/CD80. Lactoferrin treated BCG-infected BMMs were able to stimulate an increase in IFN-γ production from presensitized CD3 + splenocytes. Together, these results demonstrate that bovine lactoferrin is capable of modulating BCG-infected macrophages to enhance T-cell stimulation through increased surface expression of antigen presentation and costimulatory molecules, which potentially explains the observed in vivo bovine lactoferrin enhancement of BCG vaccine efficacy to protect against virulent MTB infection.

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Section: Discussionmentioning

confidence: 99%

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Hwang¹,

Kruzel

Actor³

2009

Biochimie

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“…Although the potential Ag85-binding site is near the link between Fn14 and Fn13, the position of Fn13 in the Fn12-Fn14 crystal structure would not sterically inhibit Ag85 binding to Fn14. This docking site fails to explain the effect of mutations at positions Leu 19 through Ser 21 , but because these residues are sandwiched between two other ␤-sheets, they are less exposed for Ag85 interactions. Also, the N-terminal end of the Ag85-binding region ( 17 SLLVSW 22 ) is more hydrophobic and therefore more likely to be involved in nonspecific binding interac- tions.…”

Section: Volume 287 • Number 3 • January 13 2012mentioning

confidence: 99%

Novel Mycobacteria Antigen 85 Complex Binding Motif on Fibronectin

Kuo

Bell

Hsieh

et al. 2012

Journal of Biological Chemistry

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“…Cationic liposomes are very efficient delivery systems for protein antigens and have recently been tested and found highly efficient for the delivery of Ag85B-ESAT-6 in various animal models of TB [30,31]. We therefore examined the effect of liposome delivery of the adenovirus constructs on the immune response induced.…”

Section: Liposome Delivery Of Adenovirus Potentiates the T Cell Respomentioning

confidence: 99%

Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

et al. 2006

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To analyze the effect of vaccine delivery systems on antigen recognition and vaccine efficacy, we compared immune responses in mice immunized either with an adenovirus vector expressing a fusion of Ag85B and ESAT-6 or with the recombinant fusion protein in a liposomal adjuvant. Both vaccines induced high levels of antigen-specific IFN-c production. The adjuvanted protein vaccine induced primarily a CD4 T cell response directed to the epitope Ag85B 241-255 and gave efficient protection against subsequent Mycobacterium tuberculosis infection. In contrast, the adenoviral construct induced a strong CD8 response predominantly targeted to the epitope ESAT-6 15-29 and no significant protection against infection. Vaccination with the protein vaccine resulted in highly accelerated recall of Ag85B 241-255 -specific T cells immediately post M. tuberculosis challenge whereas the ESAT-6 15-29 epitope was barely recognized during infection. Delivery of the viral construct in cationic liposomes switched the immune response to a protective one dominated by CD4 T cells targeted to the Ag85B [241][242][243][244][245][246][247][248][249][250][251][252][253][254][255] epitope. These data demonstrate that the nature of the T cell response to a vaccine antigen is more important than its magnitude with respect to protective efficacy and that vaccine-mediated changes in immunodominance can result in T cell responses of limited relevance during the natural infection.

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Protection of macaques against Mycobacterium tuberculosis infection by a subunit vaccine based on a fusion protein of antigen 85B and ESAT-6

Cited by 221 publications

References 38 publications

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Novel Mycobacteria Antigen 85 Complex Binding Motif on Fibronectin

Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

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