Development and Characterization of Protective
            <i>Haemophilus parasuis</i>
            Subunit Vaccines Based on Native Proteins with Affinity to Porcine Transferrin and Comparison with Other Subunit and Commercial Vaccines

Frandoloso, Rafael; Martı́nez, Sonia; Ferri, Elías Fernando Rodríguez; García‐Iglesias, M. J.; Pérez-Martínez, Claudia; Martínez-Fernández, B.; Gutiérrez-Martín, César B.

doi:10.1128/cvi.00314-10

Cited by 41 publications

(49 citation statements)

References 39 publications

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“…One study showed that a TbpA fragment from H. parasuis serovar 5 can induce an immunological response and might be useful as an antigen for a vaccine. Furthermore, the rTbpA fragment (38.5 kDa, corresponding to 200 amino acids) showed significant bactericidal activity but very poor protection partly because of the reduced length of the tpbA gene fragment (10,28). A previous study in our laboratory showed that three fragments of the rTbpA1, rTbpA2, and rTbpA3 proteins with sizes of 62, 54, and 44 kDa were successfully expressed in E. coli.…”

Section: Discussionmentioning

confidence: 99%

“…In H. parasuis, the expression of the tbpB gene has been reported. Unfortunately, the rTbpB protein gave no protection in piglets (10,24,25 useful as a candidate target for H. parasuis vaccination. One study showed that a TbpA fragment from H. parasuis serovar 5 can induce an immunological response and might be useful as an antigen for a vaccine.…”

Section: Discussionmentioning

confidence: 99%

“…The lack of effective vaccines against a broad spectrum of strains has limited disease control. With the development of modern vaccines based on molecular techniques, subunit vaccines have attracted more attention, with particular interest in the identification of proteinbased vaccine candidates (10)(11)(12). It has been shown that recombinant vaccines based on outer membrane proteins (OMPs) provided partial protection against a challenge with H. parasuis (13).…”

mentioning

confidence: 99%

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Cross-Protective Efficacy of Recombinant Transferrin-Binding Protein A of Haemophilus parasuis in Guinea Pigs

Huang

et al. 2013

Clin Vaccine Immunol

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bThe causative agent of Glasser's disease in swine is Haemophilus parasuis. Commercial bacterins are widely used for protection of the swine population. However, cross protection is limited because H. parasuis has more than 15 serovars. Transferrin-binding protein A has shown potential as a broad-spectrum vaccine candidate against homologous and heterologous strains. Here we amplified the full-length tbpA gene from an H. parasuis serovar 13 isolate and cloned it into a pET-SUMO expression vector. We then expressed and purified the TbpA protein by Ni affinity chromatography. First, the immunogenicity and protective efficacy of the protein were evaluated in guinea pigs by two subcutaneous immunizations with different doses of Montanide IMS 206 VG adjuvant. The immunized guinea pigs were, respectively, challenged on week 3 after a booster immunization with homologous strain LJ3 (serovar 13) and heterologous strain FX1 (serovar 4), and vaccine-inoculated groups were compared with nonvaccinated controls. All immunized groups showed serum antibody titers higher than those of negative-control groups. Furthermore, the cytokine and chemokine levels were evaluated at the transcriptional level by the real-time PCR analysis of six cytokines and chemokines. Gamma interferon and interleukin-5 in groups immunized with 100 g were elevated more than 15-fold over those in negative-control groups. The protection rates were 80 and 60% after a challenge with strains LJ3 and FX1, respectively, in the groups vaccinated with 100 g of recombinant TbpA protein. Subsequently, the data showed that guinea pigs immunized with a single dose (100 g) were protected at levels of 80, 80, and 60% against LJ3, FX1, and another heterologous strain, SZ (serovar 14), respectively. The results indicate for the first time that TbpA protein cross protects guinea pigs against serovars 13, 4, and 14 of H. parasuis. Taken together, these results suggest that the recombinant TbpA protein is a promising vaccine candidate that needs to be confirmed in a swine population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Cross-Protective Efficacy of Recombinant Transferrin-Binding Protein A of Haemophilus parasuis in Guinea Pigs

Huang

et al. 2013

Clin Vaccine Immunol

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“…In order to compare the immunogenicity of the H. parasuis Hp5 wild-type and Y167A mutant TbpBs, an immunization and challenge experiment was implemented similar to those performed previously (24). Groups of pigs were immunized with PBS (control group, 5 pigs), a commercial vaccine (PorcillisGlässer group, 5 pigs), the wild-type TbpB (native TbpB group, 6 pigs), or the Y167A mutant TbpB (mutant TbpB group, 6 pigs).…”

Section: Generating Tf Binding Mutants Of Tbpb With Minimal Structuramentioning

confidence: 99%

“…None of the studies with other human pathogens (19,22,23) have extended to further trials in humans, and thus they have not provided further insights into the performance of intact TbpB antigens in the natural host. Studies evaluating the potential of Tf receptor based vaccines in food production animals (20,21,24) were performed directly in the natural host and thus did not lead to questions regarding their relative performance in the natural and heterologous host.…”

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confidence: 99%

Nonbinding Site-Directed Mutants of Transferrin Binding Protein B Exhibit Enhanced Immunogenicity and Protective Capabilities

et al. 2015

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A common adaptation among several highly host-adapted Gram-negative species from the Pasteurellaceae, Neisseriaceae, and Moraxellaceae families that exclusively reside in the upper respiratory tract is the ability to directly bind host transferrin (Tf) and use it as a source of iron for growth (1, 2). Iron-loaded transferrin is captured by surface receptors that remove iron from Tf and transport the iron across the outer membrane, where it is subsequently transported into the cell through a periplasm binding protein-dependent ABC (ATP binding cassette) transport system. Early observations that the interaction of the bacterial receptors with Tf was highly host specific (3-5) provided a rational explanation for the strict host specificity of these bacterial pathogens.The initial capture of iron-loaded Tf is mediated by a surface lipoprotein, Tf binding protein B (TbpB), which consists of two structurally equivalent lobes preceded by a relatively long anchoring peptide that would allow the protein to extend far from the outer membrane surface (6). The role of TbpB is to capture the iron-loaded form of Tf and deliver it to Tf binding protein A (TbpA), the integral outer membrane protein that serves as the channel for transporting iron across the outer membrane. The structure of a Tf-TbpB complex has recently been determined (7), revealing that that the process of binding iron-loaded Tf does not involve substantial changes in the conformation of the TbpB Nlobe or the Tf C-lobe and effectively traps the Tf C-lobe in the iron-loaded state. In contrast, binding of Tf to TbpA involves substantial conformational changes in the TbpB C-lobe, resulting in substantial separation of the C1 and C2 domains that both contribute ligands for coordination of iron (8). In the absence of structural information for TbpA alone one can only speculate on the conformational changes that occur in the surface loop structures of TbpA upon binding Tf.The process by which TbpB mediates the initial capture of iron-loaded Tf and transfers it to TbpA is only partly understood. The variable association of the anchoring peptide with the C-lobe (9) and its requirement for formation of the ternary complex (10) may indicate that modulation of the anchor peptide may be involved. Although structural models can be developed for the ternary complex (2, 8), these are not based on high-resolution structural information for the actual complex, and how TbpB maintains an interaction with Tf upon domain separation is still not resolved. Similarly, the process by which iron is released and transported across the outer membrane and the degree to which different regions of TbpB participate in this process is uncertain.Since the first discovery of the bacterial Tf receptors (11, 12) and the demonstration of their exquisite host specificity (4), they were postulated to be essential for survival in the native host and thus potentially ideal vaccine targets. The importance of the receptor proteins has been confirmed in a male gonococcal infection

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The Family Pasteurellaceae

et al. 2014

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Development and Characterization of Protective Haemophilus parasuis Subunit Vaccines Based on Native Proteins with Affinity to Porcine Transferrin and Comparison with Other Subunit and Commercial Vaccines

Cited by 41 publications

References 39 publications

Cross-Protective Efficacy of Recombinant Transferrin-Binding Protein A of Haemophilus parasuis in Guinea Pigs

Cross-Protective Efficacy of Recombinant Transferrin-Binding Protein A of Haemophilus parasuis in Guinea Pigs

Nonbinding Site-Directed Mutants of Transferrin Binding Protein B Exhibit Enhanced Immunogenicity and Protective Capabilities

The Family Pasteurellaceae

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