TY  - JOUR
AU  - Minić, Rajna
AU  - Papić, Zlatko
AU  - Đorđević, Brižita
AU  - Michalickova, Danica
AU  - Ilić, Vesna
AU  - Mathiesen, Geir
AU  - Živković, Irena
AU  - Pantić, Visnja
AU  - Dimitrijević, Ljiljana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/508
AB  - The goal of this work was to elucidate similarities between microorganisms from the perspective of the humoral immune system reactivity in professional athletes. The reactivity of serum IgG of 14 young, individuals was analyzed to 23 selected microorganisms as antigens by use of the in house ELISA. Serum IgM and IgA reactivity was also analyzed and a control group of sex and age matched individuals was used for comparison. The obtained absorbance levels were used as a string of values to correlate the reactivity to different microorganisms. IgM was found to be the most cross reactive antibody class, Pearson's r = 0.7 +/- 0.92, for very distant bacterial species such as Lactobacillus and E. coli. High correlation in IgG levels was found for Gammaproteobacteria and LPS (from E. coli) (r = 0.77 for LPS vs. P. aeruginosa to r = 0.98 for LPS vs. E. coli), whereas this correlation was lower in the control group (r = 0.49 for LPS vs. P. aeruginosa to r = 0.66 for LPS vs. E. coli). The correlation was also analyzed between total IgG and IgG subclasses specific for the same microorganism, and IgG2 was identified as the main subclass recognising different microorganisms, as well as recognising LPS. Upon correlation of IgG with IgA for the same microorganism absence of or negative correlation was found between bacteria-specific IgA and IgG in case of Lactobacillus and Staphylococcusgeni, whereas correlation was absent or positive for Candida albicans, Enterococcusfaecalis, Streptococcus species tested in professional athletes. Opposite results were obtained for the control group. Outlined here is a simple experimental procedure and data analysis which yields functional significance and which can be used for determining the similarities between microorganisms from the aspect of the humoral immune system, for determining the main IgG subclass involved in an immune response as well as for the analysis of different target populations.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Profiling of microorganism-binding serum antibody specificities in professional athletes
IS  - 9
VL  - 13
DO  - 10.1371/journal.pone.0203665
ER  - 

@article{
author = "Minić, Rajna and Papić, Zlatko and Đorđević, Brižita and Michalickova, Danica and Ilić, Vesna and Mathiesen, Geir and Živković, Irena and Pantić, Visnja and Dimitrijević, Ljiljana",
year = "2018",
abstract = "The goal of this work was to elucidate similarities between microorganisms from the perspective of the humoral immune system reactivity in professional athletes. The reactivity of serum IgG of 14 young, individuals was analyzed to 23 selected microorganisms as antigens by use of the in house ELISA. Serum IgM and IgA reactivity was also analyzed and a control group of sex and age matched individuals was used for comparison. The obtained absorbance levels were used as a string of values to correlate the reactivity to different microorganisms. IgM was found to be the most cross reactive antibody class, Pearson's r = 0.7 +/- 0.92, for very distant bacterial species such as Lactobacillus and E. coli. High correlation in IgG levels was found for Gammaproteobacteria and LPS (from E. coli) (r = 0.77 for LPS vs. P. aeruginosa to r = 0.98 for LPS vs. E. coli), whereas this correlation was lower in the control group (r = 0.49 for LPS vs. P. aeruginosa to r = 0.66 for LPS vs. E. coli). The correlation was also analyzed between total IgG and IgG subclasses specific for the same microorganism, and IgG2 was identified as the main subclass recognising different microorganisms, as well as recognising LPS. Upon correlation of IgG with IgA for the same microorganism absence of or negative correlation was found between bacteria-specific IgA and IgG in case of Lactobacillus and Staphylococcusgeni, whereas correlation was absent or positive for Candida albicans, Enterococcusfaecalis, Streptococcus species tested in professional athletes. Opposite results were obtained for the control group. Outlined here is a simple experimental procedure and data analysis which yields functional significance and which can be used for determining the similarities between microorganisms from the aspect of the humoral immune system, for determining the main IgG subclass involved in an immune response as well as for the analysis of different target populations.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Profiling of microorganism-binding serum antibody specificities in professional athletes",
number = "9",
volume = "13",
doi = "10.1371/journal.pone.0203665"
}

Minić, R., Papić, Z., Đorđević, B., Michalickova, D., Ilić, V., Mathiesen, G., Živković, I., Pantić, V.,& Dimitrijević, L.. (2018). Profiling of microorganism-binding serum antibody specificities in professional athletes. in PLoS One
Public Library Science, San Francisco., 13(9).
https://doi.org/10.1371/journal.pone.0203665

Minić R, Papić Z, Đorđević B, Michalickova D, Ilić V, Mathiesen G, Živković I, Pantić V, Dimitrijević L. Profiling of microorganism-binding serum antibody specificities in professional athletes. in PLoS One. 2018;13(9).
doi:10.1371/journal.pone.0203665 .

Minić, Rajna, Papić, Zlatko, Đorđević, Brižita, Michalickova, Danica, Ilić, Vesna, Mathiesen, Geir, Živković, Irena, Pantić, Visnja, Dimitrijević, Ljiljana, "Profiling of microorganism-binding serum antibody specificities in professional athletes" in PLoS One, 13, no. 9 (2018),
https://doi.org/10.1371/journal.pone.0203665 . .

TY  - CONF
AU  - Minić, Rajna
AU  - Papić, Zlatko
AU  - Đorđević, Brižita
AU  - Michalickova, Danica
AU  - Ilić, Vesna
AU  - Mathiesen, Geir
AU  - Živković, Irena
AU  - Dimitrijević, Ljiljana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/507
PB  - Lippincott Williams & Wilkins, Philadelphia
C3  - Journal of Clinical Gastroenterology
T1  - Selected Microorganisms from an Antibody Binding Perspective in Professional Athletes
EP  - S99
SP  - S99
VL  - 52
UR  - https://hdl.handle.net/21.15107/rcub_intor_507
ER  - 

@conference{
author = "Minić, Rajna and Papić, Zlatko and Đorđević, Brižita and Michalickova, Danica and Ilić, Vesna and Mathiesen, Geir and Živković, Irena and Dimitrijević, Ljiljana",
year = "2018",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Journal of Clinical Gastroenterology",
title = "Selected Microorganisms from an Antibody Binding Perspective in Professional Athletes",
pages = "S99-S99",
volume = "52",
url = "https://hdl.handle.net/21.15107/rcub_intor_507"
}

Minić, R., Papić, Z., Đorđević, B., Michalickova, D., Ilić, V., Mathiesen, G., Živković, I.,& Dimitrijević, L.. (2018). Selected Microorganisms from an Antibody Binding Perspective in Professional Athletes. in Journal of Clinical Gastroenterology
Lippincott Williams & Wilkins, Philadelphia., 52, S99-S99.
https://hdl.handle.net/21.15107/rcub_intor_507

Minić R, Papić Z, Đorđević B, Michalickova D, Ilić V, Mathiesen G, Živković I, Dimitrijević L. Selected Microorganisms from an Antibody Binding Perspective in Professional Athletes. in Journal of Clinical Gastroenterology. 2018;52:S99-S99.
https://hdl.handle.net/21.15107/rcub_intor_507 .

Minić, Rajna, Papić, Zlatko, Đorđević, Brižita, Michalickova, Danica, Ilić, Vesna, Mathiesen, Geir, Živković, Irena, Dimitrijević, Ljiljana, "Selected Microorganisms from an Antibody Binding Perspective in Professional Athletes" in Journal of Clinical Gastroenterology, 52 (2018):S99-S99,
https://hdl.handle.net/21.15107/rcub_intor_507 .

TY  - JOUR
AU  - Kuczkowska, Katarzyna
AU  - Kleiveland, Charlotte R.
AU  - Minić, Rajna
AU  - Moen, Lars F.
AU  - Overland, Lise
AU  - Tjaland, Rannei
AU  - Carlsen, Harald
AU  - Lea, Tor
AU  - Mathiesen, Geir
AU  - Eijsink, Vincent G.H.
PY  - 2017
UR  - http://intor.torlakinstitut.com/handle/123456789/492
AB  - Tuberculosis (TB) remains among the most deadly diseases in the world. The only available vaccine against tuberculosis is the bacille Calmette-Guerin (BCG) vaccine, which does not ensure full protection in adults. There is a global urgency for the development of an effective vaccine for preventing disease transmission, and it requires novel approaches. We are exploring the use of lactic acid bacteria (LAB) as a vector for antigen delivery to mucosal sites. Here, we demonstrate the successful expression and surface display of a Mycobacterium tuberculosis fusion antigen (comprising Ag85B and ESAT-6, referred to as AgE6) on Lactobacillus plantarum. The AgE6 fusion antigen was targeted to the bacterial surface using two different anchors, a lipoprotein anchor directing the protein to the cell membrane and a covalent cell wall anchor. AgE6-producing L. plantarum strains using each of the two anchors induced antigen-specific proliferative responses in lymphocytes purified from TB-positive donors. Similarly, both strains induced immune responses in mice after nasal or oral immunization. The impact of the anchoring strategies was reflected in dissimilarities in the immune responses generated by the two L. plantarum strains in vivo. The present study comprises an initial step toward the development of L. plantarum as a vector for M. tuberculosis antigen delivery. IMPORTANCE This work presents the development of Lactobacillus plantarum as a candidate mucosal vaccine against tuberculosis. Tuberculosis remains one of the top infectious diseases worldwide, and the only available vaccine, bacille Calmette-Guerin (BCG), fails to protect adults and adolescents. Direct antigen delivery to mucosal sites is a promising strategy in tuberculosis vaccine development, and lactic acid bacteria potentially provide easy, safe, and low-cost delivery vehicles for mucosal immunization. We have engineered L. plantarum strains to produce a Mycobacterium tuberculosis fusion antigen and to anchor this antigen to the bacterial cell wall or to the cell membrane. The recombinant strains elicited proliferative antigenspecific T-cell responses in white blood cells from tuberculosis-positive humans and induced specific immune responses after nasal and oral administrations in mice.
PB  - Amer Soc Microbiology, Washington
T2  - Applied and Environmental Microbiology
T1  - Immunogenic Properties of Lactobacillus plantarum Producing Surface-Displayed Mycobacterium tuberculosis Antigens
IS  - 2
VL  - 83
DO  - 10.1128/AEM.02782-16
ER  - 

@article{
author = "Kuczkowska, Katarzyna and Kleiveland, Charlotte R. and Minić, Rajna and Moen, Lars F. and Overland, Lise and Tjaland, Rannei and Carlsen, Harald and Lea, Tor and Mathiesen, Geir and Eijsink, Vincent G.H.",
year = "2017",
abstract = "Tuberculosis (TB) remains among the most deadly diseases in the world. The only available vaccine against tuberculosis is the bacille Calmette-Guerin (BCG) vaccine, which does not ensure full protection in adults. There is a global urgency for the development of an effective vaccine for preventing disease transmission, and it requires novel approaches. We are exploring the use of lactic acid bacteria (LAB) as a vector for antigen delivery to mucosal sites. Here, we demonstrate the successful expression and surface display of a Mycobacterium tuberculosis fusion antigen (comprising Ag85B and ESAT-6, referred to as AgE6) on Lactobacillus plantarum. The AgE6 fusion antigen was targeted to the bacterial surface using two different anchors, a lipoprotein anchor directing the protein to the cell membrane and a covalent cell wall anchor. AgE6-producing L. plantarum strains using each of the two anchors induced antigen-specific proliferative responses in lymphocytes purified from TB-positive donors. Similarly, both strains induced immune responses in mice after nasal or oral immunization. The impact of the anchoring strategies was reflected in dissimilarities in the immune responses generated by the two L. plantarum strains in vivo. The present study comprises an initial step toward the development of L. plantarum as a vector for M. tuberculosis antigen delivery. IMPORTANCE This work presents the development of Lactobacillus plantarum as a candidate mucosal vaccine against tuberculosis. Tuberculosis remains one of the top infectious diseases worldwide, and the only available vaccine, bacille Calmette-Guerin (BCG), fails to protect adults and adolescents. Direct antigen delivery to mucosal sites is a promising strategy in tuberculosis vaccine development, and lactic acid bacteria potentially provide easy, safe, and low-cost delivery vehicles for mucosal immunization. We have engineered L. plantarum strains to produce a Mycobacterium tuberculosis fusion antigen and to anchor this antigen to the bacterial cell wall or to the cell membrane. The recombinant strains elicited proliferative antigenspecific T-cell responses in white blood cells from tuberculosis-positive humans and induced specific immune responses after nasal and oral administrations in mice.",
publisher = "Amer Soc Microbiology, Washington",
journal = "Applied and Environmental Microbiology",
title = "Immunogenic Properties of Lactobacillus plantarum Producing Surface-Displayed Mycobacterium tuberculosis Antigens",
number = "2",
volume = "83",
doi = "10.1128/AEM.02782-16"
}

Kuczkowska, K., Kleiveland, C. R., Minić, R., Moen, L. F., Overland, L., Tjaland, R., Carlsen, H., Lea, T., Mathiesen, G.,& Eijsink, V. G.H.. (2017). Immunogenic Properties of Lactobacillus plantarum Producing Surface-Displayed Mycobacterium tuberculosis Antigens. in Applied and Environmental Microbiology
Amer Soc Microbiology, Washington., 83(2).
https://doi.org/10.1128/AEM.02782-16

Kuczkowska K, Kleiveland CR, Minić R, Moen LF, Overland L, Tjaland R, Carlsen H, Lea T, Mathiesen G, Eijsink VG. Immunogenic Properties of Lactobacillus plantarum Producing Surface-Displayed Mycobacterium tuberculosis Antigens. in Applied and Environmental Microbiology. 2017;83(2).
doi:10.1128/AEM.02782-16 .

Kuczkowska, Katarzyna, Kleiveland, Charlotte R., Minić, Rajna, Moen, Lars F., Overland, Lise, Tjaland, Rannei, Carlsen, Harald, Lea, Tor, Mathiesen, Geir, Eijsink, Vincent G.H., "Immunogenic Properties of Lactobacillus plantarum Producing Surface-Displayed Mycobacterium tuberculosis Antigens" in Applied and Environmental Microbiology, 83, no. 2 (2017),
https://doi.org/10.1128/AEM.02782-16 . .

TY  - JOUR
AU  - Minić, Rajna
AU  - Gavrović-Jankulović, Marija
AU  - Petrušić, Vladimir
AU  - Živković, Irena
AU  - Eijsink, Vincent G.H.
AU  - Dimitrijević, Ljiljana
AU  - Mathiesen, Geir
PY  - 2015
UR  - http://intor.torlakinstitut.com/handle/123456789/447
AB  - Group I grass pollen allergens are major contributors to grass pollen-related seasonal allergic rhinitis, and as such a primary target for allergen specific immunotherapy. In this study the potential therapeutic role of oral application of Lactobacillus plantarum WCFS1, directing cell wall attachment of the recombinant Fes p1 allergen, from Festuca pratensis was tested in a mouse model of Fes p1 allergy. For surface expression of Fes p1 allergen in L. plantarum WCFS1 pSIP system with inducible expression was used. Balb/c mice were sensitized with Fes p1 protein in alum and subsequently received live recombinant L. plantarum orally. Antibody levels (IgE, total IgG, IgG1, IgG2a, and IgA) were determined by ELISA. Differential eosinophil count in peripheral blood was performed. Reduced peripheral blood eosinophilia and increased serum IgG2A levels was detected in both groups which received live L. plantarum orally. Specific serum IgA levels were increased only in mice treated with the recombinant bacteria. Oral application of L. plantarum WCFS1 has a beneficial therapeutic effect in a mouse model of Fes p1 allergy. Cell surface expression of Fes p1 allergen potentiates this phenomenon in an allergen specific way. (C) 2015 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - Journal of Biotechnology
T1  - Effects of orally applied Fes p1-displaying L. plantarum WCFS1 on Fes p1 induced allergy in mice
EP  - 28
SP  - 23
VL  - 199
DO  - 10.1016/j.jbiotec.2015.01.028
ER  - 

@article{
author = "Minić, Rajna and Gavrović-Jankulović, Marija and Petrušić, Vladimir and Živković, Irena and Eijsink, Vincent G.H. and Dimitrijević, Ljiljana and Mathiesen, Geir",
year = "2015",
abstract = "Group I grass pollen allergens are major contributors to grass pollen-related seasonal allergic rhinitis, and as such a primary target for allergen specific immunotherapy. In this study the potential therapeutic role of oral application of Lactobacillus plantarum WCFS1, directing cell wall attachment of the recombinant Fes p1 allergen, from Festuca pratensis was tested in a mouse model of Fes p1 allergy. For surface expression of Fes p1 allergen in L. plantarum WCFS1 pSIP system with inducible expression was used. Balb/c mice were sensitized with Fes p1 protein in alum and subsequently received live recombinant L. plantarum orally. Antibody levels (IgE, total IgG, IgG1, IgG2a, and IgA) were determined by ELISA. Differential eosinophil count in peripheral blood was performed. Reduced peripheral blood eosinophilia and increased serum IgG2A levels was detected in both groups which received live L. plantarum orally. Specific serum IgA levels were increased only in mice treated with the recombinant bacteria. Oral application of L. plantarum WCFS1 has a beneficial therapeutic effect in a mouse model of Fes p1 allergy. Cell surface expression of Fes p1 allergen potentiates this phenomenon in an allergen specific way. (C) 2015 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Journal of Biotechnology",
title = "Effects of orally applied Fes p1-displaying L. plantarum WCFS1 on Fes p1 induced allergy in mice",
pages = "28-23",
volume = "199",
doi = "10.1016/j.jbiotec.2015.01.028"
}

Minić, R., Gavrović-Jankulović, M., Petrušić, V., Živković, I., Eijsink, V. G.H., Dimitrijević, L.,& Mathiesen, G.. (2015). Effects of orally applied Fes p1-displaying L. plantarum WCFS1 on Fes p1 induced allergy in mice. in Journal of Biotechnology
Elsevier Science Bv, Amsterdam., 199, 23-28.
https://doi.org/10.1016/j.jbiotec.2015.01.028

Minić R, Gavrović-Jankulović M, Petrušić V, Živković I, Eijsink VG, Dimitrijević L, Mathiesen G. Effects of orally applied Fes p1-displaying L. plantarum WCFS1 on Fes p1 induced allergy in mice. in Journal of Biotechnology. 2015;199:23-28.
doi:10.1016/j.jbiotec.2015.01.028 .

Minić, Rajna, Gavrović-Jankulović, Marija, Petrušić, Vladimir, Živković, Irena, Eijsink, Vincent G.H., Dimitrijević, Ljiljana, Mathiesen, Geir, "Effects of orally applied Fes p1-displaying L. plantarum WCFS1 on Fes p1 induced allergy in mice" in Journal of Biotechnology, 199 (2015):23-28,
https://doi.org/10.1016/j.jbiotec.2015.01.028 . .

TY  - JOUR
AU  - Dimitrijević, Rajna
AU  - Ivanović, Nevena
AU  - Mathiesen, Geir
AU  - Petrušić, Vladimir
AU  - Živković, Irena
AU  - Đorđević, Brižita
AU  - Dimitrijević, Ljiljana
PY  - 2014
UR  - http://intor.torlakinstitut.com/handle/123456789/398
AB  - Probiotic bacteria have been used in human nutrition for centuries and are now attracting more attention. In order to examine the immunological aspects of probiotic consumption, Lactobacillus rhamnosus LA68 was orally administrated using gavage to healthy C57BL/6 mice. After one month splenocytes were isolated, and analysed by flow cytometry. The magnitude of splenocyte proliferation upon stimulation with lipopolysaccharide and peptidoglycan and cytokine levels (IFN-gamma, IL-6, IL-10 and IL-17) was assessed. Cytokine levels in the serum were also analysed. Oral application of strain LA68 leads to a significant decrease of CD3+, CD25+ and CD19+ cells, and an increase of CD11b+ and CD16/CD32+ positive cell populations in the mouse spleen. Increased sensitivity to stimulation through proliferation and IL-6 secretion was detected. Increased serum IFN-gamma and decreased IL-10 levels were found. Our results show increased responsiveness of splenocytes, activation of the Th1 type of immune response, and a shift of leucocyte populations towards monocyte/granulocyte populations.
PB  - Cambridge Univ Press, New York
T2  - Journal of Dairy Research
T1  - Effects of Lactobacillus rhamnosus LA68 on the immune system of C57BL/6 mice upon oral administration
EP  - 207
IS  - 2
SP  - 202
VL  - 81
DO  - 10.1017/S0022029914000028
ER  - 

@article{
author = "Dimitrijević, Rajna and Ivanović, Nevena and Mathiesen, Geir and Petrušić, Vladimir and Živković, Irena and Đorđević, Brižita and Dimitrijević, Ljiljana",
year = "2014",
abstract = "Probiotic bacteria have been used in human nutrition for centuries and are now attracting more attention. In order to examine the immunological aspects of probiotic consumption, Lactobacillus rhamnosus LA68 was orally administrated using gavage to healthy C57BL/6 mice. After one month splenocytes were isolated, and analysed by flow cytometry. The magnitude of splenocyte proliferation upon stimulation with lipopolysaccharide and peptidoglycan and cytokine levels (IFN-gamma, IL-6, IL-10 and IL-17) was assessed. Cytokine levels in the serum were also analysed. Oral application of strain LA68 leads to a significant decrease of CD3+, CD25+ and CD19+ cells, and an increase of CD11b+ and CD16/CD32+ positive cell populations in the mouse spleen. Increased sensitivity to stimulation through proliferation and IL-6 secretion was detected. Increased serum IFN-gamma and decreased IL-10 levels were found. Our results show increased responsiveness of splenocytes, activation of the Th1 type of immune response, and a shift of leucocyte populations towards monocyte/granulocyte populations.",
publisher = "Cambridge Univ Press, New York",
journal = "Journal of Dairy Research",
title = "Effects of Lactobacillus rhamnosus LA68 on the immune system of C57BL/6 mice upon oral administration",
pages = "207-202",
number = "2",
volume = "81",
doi = "10.1017/S0022029914000028"
}

Dimitrijević, R., Ivanović, N., Mathiesen, G., Petrušić, V., Živković, I., Đorđević, B.,& Dimitrijević, L.. (2014). Effects of Lactobacillus rhamnosus LA68 on the immune system of C57BL/6 mice upon oral administration. in Journal of Dairy Research
Cambridge Univ Press, New York., 81(2), 202-207.
https://doi.org/10.1017/S0022029914000028

Dimitrijević R, Ivanović N, Mathiesen G, Petrušić V, Živković I, Đorđević B, Dimitrijević L. Effects of Lactobacillus rhamnosus LA68 on the immune system of C57BL/6 mice upon oral administration. in Journal of Dairy Research. 2014;81(2):202-207.
doi:10.1017/S0022029914000028 .

Dimitrijević, Rajna, Ivanović, Nevena, Mathiesen, Geir, Petrušić, Vladimir, Živković, Irena, Đorđević, Brižita, Dimitrijević, Ljiljana, "Effects of Lactobacillus rhamnosus LA68 on the immune system of C57BL/6 mice upon oral administration" in Journal of Dairy Research, 81, no. 2 (2014):202-207,
https://doi.org/10.1017/S0022029914000028 . .