Sequence and structural diversity of transferrin receptors in Gram-negative porcine pathogens

Curran, David M.; Adamiak, Paul; Fegan, Jamie E.; Qian, Chenzhe; Yu, Rong-hua; Schryvers, Anthony B.

doi:10.1016/j.vaccine.2015.07.097

Cited by 17 publications

(39 citation statements)

References 31 publications

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“…For interpretation of the cross-reactivity of the sera (Fig. 1B ), it is important to recognize that there is considerable sequence diversity of the TbpBs that is independent of serovar 19 and that relatively high levels of Tf in sera that could compete for epitopes in the binding region. Notably there are cross-reactive epitopes present on both the N-lobe and C-lobe of TbpB expressed on the surface of different H. parasuis strains (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Since TbpB is a lipoprotein anchored to the outer membrane by the N-terminal anchor peptide region, both lobes of the protein may be accessible to antibody and other immune effector mechanisms. Thus, it is an important question as to whether less variable regions of the protein, primarily located in the C-lobe 19 , could be used to induce a more cross-protective response. Groups of pigs (6 per antigen) were immunized with the intact wild-type TbpB, Y167A mutant TbpB or with its constituent mutant N-lobe or C-lobe and were subjected to intratracheal challenge with 10 8 CFU of H. parasuis Nagasaki strain, along with control pigs (6 animals) treated with PBS + Montanide IMS 2215 VG PR.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, in pathogens such as H. parasuis that have variable and exchangeable surface antigens, whole-cell vaccines formulated with one or more serovars demonstrate variable degrees of protection 3 , 4 , 23 , 24 which might be limited by the type of adjuvant used 24 . The demonstration that antigenic variants of the Tf receptor proteins are distributed amongst three porcine pathogens, H. parasuis , A. pleuropneumoniae and A. suis 19 , indicates that reservoirs of antigenic variants outside of H. parasuis must be considered during the development of broadly cross-protective and long-lasting vaccines.…”

Section: Discussionmentioning

confidence: 99%

“…Follow up experiments suggested that the primary mechanism for superior protection induced by the mutant TbpB was a stronger T helper 2 response 18 . Analysis of the sequence and structural diversity of TbpBs from H. parasuis, A. pleuropneumoniae and A. suis revealed that this diversity was not associated with geographic region or species and that immunization with intact TbpB generated a substantially greater cross-reactive antibody response compared to the N-lobe, correlating with relative sequence and structural diversity 19 . The aim of this study was to evaluate whether these findings translate into functional antibody responses that could provide a foundation for developing broadly cross-protective vaccines.…”

Section: Introductionmentioning

confidence: 99%

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New insights about functional and cross-reactive properties of antibodies generated against recombinant TbpBs of Haemophilus parasuis

Barasuol

Guizzo

Fegan

et al. 2017

Sci Rep

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Vaccines have become fundamental in the control and elimination of Glässer Disease, a systemic disease of pigs caused by Haemophilus parasuis. The classic vaccines available for prevention of this infection were developed without a robust knowledge about host immunological mechanisms. In this study, we demonstrated the presence of cross-reactive epitopes on both the N-lobe and C-lobe of variants of transferrin binding protein B (TbpBs) expressed on the surface of 6 virulent serovars of H. parasuis. Antibodies against TbpB-derived antigens were capable of increasing the phagocytic capacity of neutrophils and were also capable of blocking porcine transferrin from binding to TbpB. Surprisingly, none of the pig or mice antisera from animals immunized with TbpB-derived antigens mixed with Montanide IMS 2215 VG PR adjuvant were able to activate the classical complement pathway (CCP). In contrast, antisera from mice immunized with TbpB-derived antigens adjuvanted with Freund’s adjuvants or Montanide Gel 01 were able to activate the CCP and kill H. parasuis. Our results demonstrate that the type of adjuvant can modulate the functional response induced by TbpB-derived antigens. Based on these results, we propose that a properly formulated TbpB-based vaccine may elicit a functional protective antibody response with broad cross-reactivity against heterologous strains of H. parasuis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

New insights about functional and cross-reactive properties of antibodies generated against recombinant TbpBs of Haemophilus parasuis

Barasuol

Guizzo

Fegan

et al. 2017

Sci Rep

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show abstract

“…Sera from CH, nTbpB, Y167A and CB pigs were added at a 1:100 dilution and incubated for 60 min at room temperature. After washing with PBST, goat anti-swine IgG (Sigma, Madrid, Spain) horseradish peroxidase-conjugated antibody at a 1:10,000 dilution was added, and the plates were developed at 450 nm (Curran et al, 2015).…”

Section: Enzyme-linked Immunosorbent Assays (Elisas)mentioning

confidence: 99%

A vaccine based on a mutant transferrin binding protein B of Haemophilus parasuis induces a strong T-helper 2 response and bacterial clearance after experimental infection

Martínez-Martínez

Frandoloso

Ferri

et al. 2016

Veterinary Immunology and Immunopathology

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This study aimed to characterize the type of immune response induced by an experimental vaccine based on a mutant Haemophilus parasuis transferrin binding protein (Tbp) B (Y167A) defective in its ability to bind porcine transferrin. Clinical and pathological signs, bacterial clearance, antibody response and the cytokine profile in alveolar macrophages and spleen after the vaccination and challenge of twenty-two colostrum-deprived pigs with 10(8) CFU of H. parasuis were analysed. Pigs vaccinated with Y167A were compared to those vaccinated with native TbpB (nTbpB), those treated with a commercial bacterin (CB) against Glässer's disease, those unvaccinated challenged (CH) and those unvaccinated unchallenged (UNCH) pigs. The rectal temperatures of Y167A pigs resembled those of UNCH pigs and were significantly lower than those of the nTbpB, CB and CH animals. A major reduction in pathological changes of the challenged pigs was observed in the Y167A group. H. parasuis was cleared from 88.9% of the samples from Y167A pigs versus 60.0% and 55.6% from those of the CB and nTbpB groups, respectively. The antibody response elicited by Y167A by ELISA was notably higher than that observed for nTbpB and CB pigs and was capable of preventing the expression and secretion of IL-8. The expression of IL-4 and IL-5, which were associated with the specific antibody levels, suggests that the main mechanism of protection conferred by Y167A vaccine is based on a strong T-helper 2 response.

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Are lactoferrin receptors in Gram-negative bacteria viable vaccine targets?

Chan

Andisi

et al. 2018

Biometals

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A number of important Gram-negative pathogens that reside exclusively in the upper respiratory or genitourinary tract of their mammalian host rely on surface receptors that specifically bind host transferrin and lactoferrin as a source of iron for growth. The transferrin receptors have been targeted for vaccine development due to their critical role in acquiring iron during invasive infection and for survival on the mucosal surface. In this study, we focus on the lactoferrin receptors, determining their prevalence in pathogenic bacteria and comparing their prevalence in commensal Neisseria to other surface antigens targeted for vaccines; addressing the issue of a reservoir for vaccine escape and impact of vaccination on the microbiome. Since the selective release of the surface lipoprotein lactoferrin binding protein B by the NalP protease in Neisseria meningitidis argues against its utility as a vaccine target, we evaluated the release of outer membrane vesicles, and transferrin and lactoferrin binding in N. meningitidis and Moraxella catarrhalis. The results indicate that the presence of NalP reduces the binding of transferrin and lactoferrin by cells and native outer membrane vesicles, suggesting that NalP may impact all lipoprotein targets, thus this should not exclude lactoferrin binding protein B as a target.

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Sequence and structural diversity of transferrin receptors in Gram-negative porcine pathogens

Cited by 17 publications

References 31 publications

New insights about functional and cross-reactive properties of antibodies generated against recombinant TbpBs of Haemophilus parasuis

New insights about functional and cross-reactive properties of antibodies generated against recombinant TbpBs of Haemophilus parasuis

A vaccine based on a mutant transferrin binding protein B of Haemophilus parasuis induces a strong T-helper 2 response and bacterial clearance after experimental infection

Are lactoferrin receptors in Gram-negative bacteria viable vaccine targets?

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