Vaccine Candidates against Nontypeable  Haemophilus influenzae: a Review

Behrouzi, Ava; Vaziri, Farzam; Jamnani, Fatemeh Rahimi; Afrough, Parviz; Rahbar, Mohammad; Satarian, Fereshteh; Siadat, Seyed Davar

doi:10.18869/acadpub.ibj.21.2.69

Cited by 17 publications

(18 citation statements)

References 72 publications

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“…Efforts to develop a successful vaccine against NTHi are ongoing, with several antigenic virulence factors that contribute to the early stages of bacterial colonization under consideration as potential vaccine candidates (11)(12)(13). Several proteins are under investigation as vaccine candidates (11,14), including fimbriae (OMP P5-homologous fimbriae (15)), outer membrane proteins (OMPs) (P2, P6) (16,17), transferrin binding proteins (TbpB) (18), protein D (19), PilA (major subunit of type IV pili) (20), Hia (21), Hap (22), and HMW1/2 (14,23). However, vaccine development is impeded by the high variability and heterogeneity of NTHi, especially of their surface molecules (13,24).…”

Section: Introductionmentioning

confidence: 99%

Phase-Variable Glycosylation in Nontypeable Haemophilus influenzae

Elango

Schulz

2019

J. Proteome Res.

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Non-typeable Haemophilus influenzae (NTHi) is a leading cause of respiratory tract infections worldwide and continues to be a global health burden. Adhesion and colonisation of host cells are crucial steps in bacterial pathogenesis, and in many strains of NTHi interaction with the host is mediated by the high molecular weight adhesins HMW1A and HMW2A. These adhesins are N-glycoproteins which are modified by cytoplasmic glycosyltransferases HMW1C and HMW2C. Phase variation in the number of short sequence repeats in the promoters of hmw1A and hmw2A directly affects their expression. Here, we report the presence of similar variable repeat elements in the promoters of hmw1C and hmw2C in diverse NTHi isolates. In an ex vivo assay, we systematically altered substrate and glycosyltransferase expression and showed that both of these factors affected the site-specific efficiency of glycosylation on HMW-A. Glycosylation occupancy was incomplete at many sites, variable between sites, and generally lower close to the C-terminus of HMW-A. We investigated the causes of this variability. As HMW-C glycosylates HMW-A in the cytoplasm, we tested how secretion affected glycosylation on HMW-A and showed that retaining HMW-A in the cytoplasm indeed increased glycosylation occupancy across the full length of the protein. Sitedirected mutagenesis showed that HMW-C had no inherent preference for glycosylating asparagines in NxS or NxT sequons. This work provides key insights into factors contributing to the heterogenous modifications of NTHi HMW-A adhesins, expands knowledge of NTHi population diversity and pathogenic capability, and is relevant to vaccine design for NTHi and related pathogens..

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Section: Introductionmentioning

confidence: 99%

Phase-Variable Glycosylation in Nontypeable Haemophilus influenzae

Elango

Schulz

2019

J. Proteome Res.

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“…This was followed by the prediction of the location of the highly antigenic epitopes within the cellular structure and docking of selected epitopes with common human allele DRB1*0101. Immunological studies revealed the detection of antibodies against OMPs and LPSs in human serum, thereby, indicating them to be ideal candidates for the activation of humoral immunity hence making them excellent candidates for vaccine development (Behrouzi et al 2017). In the present study, focus was on the prioritization of the outer membrane proteins as vaccine candidates.…”

Section: Discussionmentioning

confidence: 99%

“…These factors, therefore, stress the need for designing and developing effective vaccine candidates against the bacterial strains ( Ulanova et al 2012;Behrouzi et al 2017). Of the various immunogenic biomolecular components, utilizing outer membrane proteins, can serve as an effective candidate for vaccine development (Van Eldere et al 2014).…”

Section: R a F Tmentioning

confidence: 99%

Vaccinomics-driven proteome-wide screening of Haemophilus influenzae for the prediction of common putative vaccine candidates

Bibi¹,

Zaidi²,

Tahir³

et al. 2021

Can. J. Microbiol.

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Haemophilus influenzae colonizes the respiratory tract and is associated with life-threatening invasive infections. The recent rise in its global prevalence, even in the presence of multiple vaccines, indicate an urgent need for developing cross-strain effective vaccine strategies. Our work focused on identifying the universally conserved antigenic regions of H. influenzae that can be used for developing new vaccines. A variety of bioinformatics tools were applied for the comprehensive geno-proteomic analysis of H. influenzae type “a” strain, as reference serotype, through which subcellular localization, essentiality, virulence, and non-host homology were determined. B and T-Cell epitope mapping of 3D protein structures were performed. Thereafter, molecular docking with HLA DRB1*0101 and comparative genome analysis established the candidature of identified regions. Based on the established vaccinomics criteria, five target proteins were predicted as novel vaccine candidates. Among these, 9 epitopic regions were identified that could regulate the lymphocyte activity through strong protein-protein interactions. Comparative genomic analysis exhibited that the identified regions were highly conserved among the different strains of H. influenzae. Based on multiple immunogenic factors, the five prioritized proteins and their predicted epitopes were identified as the ideal common putative vaccine candidate against typeable strains.

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“…In 1931, Avery and Goebel first reported that the conjugation of capsular polysaccharides from Type III pneumococcus to the carrier protein could elicit the production of polysaccharide‐specific IgG antibodies and the long‐lasting immune response . Since then, a similar principle has been successfully applied to various bacteria such as Neisseria meningitidis , Haemophillus infuenzae type b (Hib), and Salmonella enterica serovar typhi . The extensively‐used carrier proteins include tetanus toxoid (TT), diphtheria toxoid (DT), diphtheria toxin derivative (CRM197), keyhole limpet hemocyanin (KLH), bovine serum albumin (BSA), human serum albumin (HSA) and so on.…”

Section: Synthetic Carbohydrate‐based Vaccinesmentioning

confidence: 99%

Synthetic Glycans and Glycomimetics: A Promising Alternative to Natural Polysaccharides

Zhang

2018

Chemistry A European J

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A large quantity of polysaccharide-derived conjugate vaccines have been developed to combat various pathogenic infections. Another prominent polysaccharide, heparin, is listed as an essential drug by the World Health Organization (WHO) to treat thrombus. One of their common problems is that they all derive from natural polysaccharides. Specifically, capsular polysaccharides are mainly obtained from bacterial fermentation and unfractionated heparin is extracted from animal tissues such as porcine mucosa. The quality of natural polysaccharides is inconsistent and traces of contamination would cause a disaster. By contrast, the use of chemical or chemoenzymatic methods could provide structurally homogeneous and quality-controlled glycans. To date, large numbers of polysaccharide fragments and their analogues have been synthesized and evaluated. Some of them even showed comparable activities to their corresponding natural polysaccharides. Here, the latest advances in these synthetic glycan analogues ranging from carbohydrate-based vaccines, heparin-related therapeutics and glycomimetics of polysaccharides are summarized.

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Vaccine Candidates against Nontypeable Haemophilus influenzae: a Review

Cited by 17 publications

References 72 publications

Phase-Variable Glycosylation in Nontypeable Haemophilus influenzae

Phase-Variable Glycosylation in Nontypeable Haemophilus influenzae

Vaccinomics-driven proteome-wide screening of Haemophilus influenzae for the prediction of common putative vaccine candidates

Synthetic Glycans and Glycomimetics: A Promising Alternative to Natural Polysaccharides

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