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Vaccines
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The Current Development of Glycoconjugate Vaccines for Infectious Diseases
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The Current Development of Glycoconjugate Vaccines for Infectious Diseases

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against Tropical and other Infectious Diseases".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 4820

Special Issue Editor

Dr. Fatme Mawas

E-Mail Website
Guest Editor
Vaccines Division, Science, Research & Innovation Group, MHRA, Potters Bar, UK
Interests: conjugate vaccines; mucosal delivery; immunoassays; correlates of protection

Special Issue Information

Dear Colleagues,

Glycoconjugate vaccines were successful against H. influenzae b (Hib) in the 1980s, leading to the development of other conjugate vaccines. However, chemical conjugation has limitations such as variability, high costs, and low recovery. Identifying alternative carrier proteins or systems is desirable. Biological conjugation, such as glycoengineering of recombinant vaccines in bacteria, bypasses these issues. Another alternative method is using Multiple Antigen Presenting Systems (MAPS) to produce glycoconjugate vaccines. This special issue highlights recent scientific knowledge and progress in the field of conjugate vaccines.

In this special issue on conjugate vaccines, we invite you to contribute an original report, observation, or review. Your contribution should focus on the development and evaluation of conjugate vaccines against infectious diseases, novel carrier proteins, recent advances in production technologies, and improvements in characterization methods. Specifically,

  1. development and evaluation of conjugate vaccines against infectious diseases,
  2. novel carrier proteins,
  3. recent advances in novel technologies for conjugate vaccine production,
  4. improvements in methods for conjugate vaccine characterization.

Dr. Fatme Mawas
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bacterial vaccines
  • polysaccharides
  • conjugate vaccines
  • carrier proteins

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Published Papers (3 papers)

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Research

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15 pages, 2037 KiB  
Article
Modular Combinatorial DNA Assembly of Group B Streptococcus Capsular Polysaccharide Biosynthesis Pathways to Expediate the Production of Novel Glycoconjugate Vaccines
by Mark A. Harrison, Elizabeth Atkins, Alexandra Faulds-Pain, John T. Heap, Brendan W. Wren and Ian J. Passmore
Vaccines 2025, 13(3), 279; https://doi.org/10.3390/vaccines13030279 - 6 Mar 2025
Viewed by 1018
Abstract
Background/objectives: Streptococcus agalactiae (or Group B Streptococcus, GBS) is a major cause of neonatal meningitis globally. There are 10 serotypes of GBS, which are distinguished by their capsular polysaccharide (CPS) structure, with serotypes Ia, Ib, II, III, IV and V responsible for up [...] Read more.
Background/objectives: Streptococcus agalactiae (or Group B Streptococcus, GBS) is a major cause of neonatal meningitis globally. There are 10 serotypes of GBS, which are distinguished by their capsular polysaccharide (CPS) structure, with serotypes Ia, Ib, II, III, IV and V responsible for up to 99% of infections. Currently, there are no licensed vaccines against GBS. The most developed candidates are glycoconjugate vaccines, which can be highly effective but are also expensive to produce by existing approaches and unaffordable for many parts of the world. Biosynthesis of recombinant glycans and glycoconjugates in tractable strains of bacteria offers a low-cost alternative approach to current chemical conjugation methods. Methods: In this study, we apply combinatorial hierarchical DNA assembly to the heterologous biosynthesis of GBS III, IV and V CPSs in E. coli. Each gene was removed from its native regulation, paired with synthetic regulatory elements and rebuilt from the bottom up to generate libraries of reconstituted pathways. These pathways were screened for glycan biosynthesis using serotype-specific antisera. Results: We identified several configurations that successfully biosynthesised the GBS CPSs. Furthermore, we exploited the conserved nature of the GBS CPS biosynthesis loci and the flexibility of modular DNA assembly by constructing hybrid pathways from a minimal pool of glycosyltransferase genes. We show that transferase genes with homologous function can be used interchangeably between pathways, obviating the need to clone a complete locus for each new CPS assembly. Conclusions: In conclusion, we report the first demonstration of heterologous GBS CPS IV and V biosynthesis in E. coli, a key milestone towards the development of low-cost recombinant multivalent GBS glycoconjugate vaccines. Full article
(This article belongs to the Special Issue The Current Development of Glycoconjugate Vaccines for Infectious Diseases)
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17 pages, 955 KiB  
Article
Further Insights into the Measurement of Free Polysaccharide in Meningococcal Conjugate Vaccines
by Nicola J. Beresford, Gianluigi De Benedetto, Kay Lockyer, Fang Gao, Karena Burkin, Karan Lalwani and Barbara Bolgiano
Vaccines 2025, 13(2), 167; https://doi.org/10.3390/vaccines13020167 - 9 Feb 2025
Cited by 1 | Viewed by 1131
Abstract
Objectives: The purpose of this study was to further characterize the ultrafiltration (UF) method for determining free saccharide levels in glycoconjugate vaccines and compare it with other methods used for the determination of free saccharide levels in meningococcal glycoconjugate vaccines. Methods: [...] Read more.
Objectives: The purpose of this study was to further characterize the ultrafiltration (UF) method for determining free saccharide levels in glycoconjugate vaccines and compare it with other methods used for the determination of free saccharide levels in meningococcal glycoconjugate vaccines. Methods: We performed experiments on both meningococcal glycoconjugates and capsular polysaccharides, and compared UF, deoxycholate (DOC) precipitation, and solid-phase extraction (SPE) methods. Meningococcal capsular polysaccharides from groups A (MenA), C (MenC), and W (MenW) were depolymerized and characterized using SEC-MALS (size-exclusion chromatography with multi-angle laser light scattering) to determine the molecular weight and hydrodynamic size and then subjected to UF. The free saccharide content was quantified using HPAEC-PAD (high-performance anion-exchange chromatography with pulsed amperometric detection). Results: The characterization of size-reduced group C polysaccharide revealed weight-average molecular mass (Mw) ranging from 22,200 g/mol to 287,300 g/mol and hydrodynamic radii of 3.7 to 19.5 nm. Pore size studies confirmed that polysaccharides with diameters up to 15 nm filtered through the 100 kDa cellulose membrane. The smallest PS fragment tested (22,200 g/mol, 7.4 nm diameter) was partially recovered from the 30 kDa membrane. For MenC-CRM197, DOC yielded the lowest free saccharide content (<1%), UF gave moderate results (7–8%), and SPE showed the highest and most variable values (up to 15%). For MenA- and MenW-CRM197, UF and DOC consistently provided low free saccharide levels (<2% and 3–11%, respectively). Conclusions: The upper limits on the size of free group C meningococcal polysaccharides that can be ultrafiltered were assessed. Differences in the relative amount of free saccharide were observed between various methods used to control meningococcal conjugate vaccines. Full article
(This article belongs to the Special Issue The Current Development of Glycoconjugate Vaccines for Infectious Diseases)
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Review

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18 pages, 2038 KiB  
Review
Analytical Challenges in Novel Pentavalent Meningococcal Conjugate Vaccine (A, C, Y, W, X)
by Pankaj Sharma, Sameer Kale, Swapnil Phugare, Sunil Kumar Goel and Sunil Gairola
Vaccines 2024, 12(11), 1227; https://doi.org/10.3390/vaccines12111227 - 29 Oct 2024
Cited by 2 | Viewed by 1964
Abstract
Multivalent meningococcal conjugate vaccines are a significant focus for the scientific community in light of the WHO’s mission to defeat meningitidis by 2030. Well-known meningococcal vaccines such as MenAfriVac, Nimenrix, Menveo, and MenQuadfi are licensed in various parts of the world and have [...] Read more.
Multivalent meningococcal conjugate vaccines are a significant focus for the scientific community in light of the WHO’s mission to defeat meningitidis by 2030. Well-known meningococcal vaccines such as MenAfriVac, Nimenrix, Menveo, and MenQuadfi are licensed in various parts of the world and have been successful. Recently, the World Health Organization (WHO) qualified MenFive (meningococcal A, C, Y, W, and X) conjugate vaccine, further enhancing the battery of vaccines against meningitis. The antigenic nature of the current and new serogroups, the selection of carrier proteins, and the optimal formulation of these biomolecules are pivotal parameters for determining whether a biological preparation qualifies as a vaccine candidate. Creating appropriate quality control analytical tools for a complex biological formulation is challenging. A scoping review aims to identify the main challenges and gaps in analyzing multivalent vaccines, especially in the case of novel serogroups, such as X, as the limited literature addresses these analytical challenges. In summary, the similarities in polysaccharide backbones between meningococcal serogroups (C, Y, W sharing a sialic acid backbone and A, X sharing a phosphorous backbone) along with various conjugation chemistries (such as CNBr activation, reductive amination, CDAP, CPIP, thioether bond formation, N-hydroxy succinimide activation, and carbodiimide-mediated coupling) resulting into a wide variety of polysaccharide -protein conjugates. The challenge in analyzing carrier proteins used in conjugation (such as diphtheria toxoid, tetanus toxoid, CRM diphtheria protein, and recombinant CRM) is assessing their purity (whether they are monomeric or polymeric in nature as well as their polydispersity). Additional analytical challenges include the impact of excipients, potential interference from serogroups, selection and establishment of standards, age-dependent behavior of biomolecules indicated by molecular size distributions, and process-driven variations. This article explains the analytical insights gained (polysaccharide content, free saccharide, free proteins, MSD) during the development of the MenFive vaccine and highlights the crucial gaps and challenges in testing. Full article
(This article belongs to the Special Issue The Current Development of Glycoconjugate Vaccines for Infectious Diseases)
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