Investigating the candidacy of lipopolysaccharide-based glycoconjugates as vaccines to combat Mannheimia haemolytica

Michael, Frank St.; Cairns, Chantelle M.; Filion, Amy Lea; Dhamodharan, Neelamegan; Lacelle, Suzanne; Cox, Andrew D.

doi:10.1007/s10719-011-9339-0

Cited by 10 publications

(5 citation statements)

References 31 publications

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“…This may be because bovine M. haemolytica isolates often do not elaborate an O-antigen, which is the most immunogenic component of LPS (Ali et al ., 1992). Alternatively, the core lipopolysaccharide of M. haemolytica LPS has been analyzed, and glycoconjugates of LPS core were shown to be immunogenic in rabbits and stimulated complement-mediated killing of M. haemolytica (St Michael et al ., 2011 a , 2011 b ).…”

Section: Virulence Factors and Potential Immunogensmentioning

confidence: 99%

Mannheimia haemolyticain bovine respiratory disease: immunogens, potential immunogens, and vaccines

Confer

Ayalew

2018

Anim. Health. Res. Rev.

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Mannheimia haemolytica is the major cause of severe pneumonia in bovine respiratory disease (BRD). Early M. haemolytica bacterins were either ineffective or even enhanced disease in vaccinated cattle, which led to studies of the bacterium's virulence factors and potential immunogens to determine ways to improve vaccines. Studies have focused on the capsule, lipopolysaccharide, various adhesins, extracellular enzymes, outer membrane proteins, and leukotoxin (LKT) resulting in a strong database for understanding immune responses to the bacterium and production of more efficacious vaccines. The importance of immunity to LKT and to surface antigens in stimulating immunity led to studies of individual native or recombinant antigens, bacterial extracts, live-attenuated or mutant organisms, culture supernatants, combined bacterin-toxoids, outer membrane vesicles, and bacterial ghosts. Efficacy of several of these potential vaccines can be shown following experimental M. haemolytica challenge; however, efficacy in field trials is harder to determine due to the complexity of factors and etiologic agents involved in naturally occurring BRD. Studies of potential vaccines have led current commercial vaccines, which are composed primarily of culture supernatant, bacterin-toxoid, or live mutant bacteria. Several of those can be augmented experimentally by addition of recombinant LKT or outer membrane proteins.

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Section: Virulence Factors and Potential Immunogensmentioning

confidence: 99%

Mannheimia haemolyticain bovine respiratory disease: immunogens, potential immunogens, and vaccines

Confer

Ayalew

2018

Anim. Health. Res. Rev.

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“…Knowing that the semisynthetic conjugates were immunogenic, we next assessed whether the generic spacer moiety (composed of ethyl and adipoyl groups) connecting the synthetic oligosaccharides to the CRM 197 protein was immunogenic. It was shown previously that strong spacer-specific antibody responses can suppress antibody responses to weakly immunogenic oligosaccharide antigens, which may explain the relatively poor immunogenicity of the 1RU ( 1 ) and FS1 ( 4 ) antigens. , To this end, we prepared conjugates with the bovine serum albumin (BSA) protein and five different monosaccharides with C2, C5, or polyethylene glycol linkers (see Figure S2 in the Supporting Information). The resulting BSA conjugates prepared with the C2-linked monosaccharides contain a generic spacer moiety that is identical to that of the semisynthetic CRM 197 conjugates used for vaccination experiments.…”

Section: Resultsmentioning

confidence: 99%

Semisynthetic Glycoconjugate Vaccine Candidates against Escherichia coli O25B Induce Functional IgG Antibodies in Mice

Naini¹,

Bartetzko²,

Sanapala³

et al. 2022

JACS Au

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Extraintestinal pathogenic Escherichia coli (ExPEC) is a major health concern due to emerging antibiotic resistance. Along with O1A, O2, and O6A, E. coli O25B is a major serotype within the ExPEC group, which expresses a unique O -antigen. Clinical studies with a glycoconjugate vaccine of the above-mentioned O -types revealed O25B as the least immunogenic component, inducing relatively weak IgG titers. To evaluate the immunological properties of semisynthetic glycoconjugate vaccine candidates against E. coli O25B, we here report the chemical synthesis of an initial set of five O25B glycan antigens differing in length, from one to three repeat units, and frameshifts of the repeat unit. The oligosaccharide antigens were conjugated to the carrier protein CRM 197 . The resulting semisynthetic glycoconjugates induced functional IgG antibodies in mice with opsonophagocytic activity against E. coli O25B. Three of the oligosaccharide–CRM 197 conjugates elicited functional IgGs in the same order of magnitude as a conventional CRM 197 glycoconjugate prepared with native O25B O -antigen and therefore represent promising vaccine candidates for further investigation. Binding studies with two monoclonal antibodies (mAbs) revealed nanomolar anti-O25B IgG responses with nanomolar K D values and with varying binding epitopes. The immunogenicity and mAb binding data now allow for the rational design of additional synthetic antigens for future preclinical studies, with expected further improvements in the functional antibody responses. Moreover, acetylation of a rhamnose residue was shown to be likely dispensable for immunogenicity, as a deacylated antigen was able to elicit strong functional IgG responses. Our findings strongly support the feasibility of a semisynthetic glycoconjugate vaccine against E. coli O25B.

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“…The maleimide-thiol conjugation chemistry has the potential advantage of low immunogenicity. Anti-maleimide linker immune response has been detected where maleimide derivatives containing certain chemical groups associated with the maleimide function were used, eg, 4-( p -maleimidophenyl)butyrate (MPB), m -maleimidobenzoate (MBS), or 4-( N -maleimidomethyl)-cyclohexane-l-carboxylate (MCC) [ 14 – 16 ]. In this study, we used (simple) maleimides (present in DSPE-PEG2000-Maleimide and NEM) in preference to maleimide derivatives, to avoid immunogenic/toxic side-effects due to the presence of additional/unnecessary chemical groups associated with the maleimide linker.…”

Section: Discussionmentioning

confidence: 99%

A Targeting Microbubble for Ultrasound Molecular Imaging

et al. 2015

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RationaleMicrobubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld.ObjectiveTo develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging.Methods and ResultsMicrobubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab’)2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification.ConclusionsTargeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i)–(iii) desired for clinical applications.

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Investigating the candidacy of lipopolysaccharide-based glycoconjugates as vaccines to combat Mannheimia haemolytica

Cited by 10 publications

References 31 publications

Mannheimia haemolyticain bovine respiratory disease: immunogens, potential immunogens, and vaccines

Mannheimia haemolyticain bovine respiratory disease: immunogens, potential immunogens, and vaccines

Semisynthetic Glycoconjugate Vaccine Candidates against Escherichia coli O25B Induce Functional IgG Antibodies in Mice

A Targeting Microbubble for Ultrasound Molecular Imaging

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