Advances in Glycoconjugate Vaccines and Nanovaccines

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: 31 August 2025 | Viewed by 8690

Special Issue Editors


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Guest Editor
Department of Drug Sciences, School of Pharmacy, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy
Interests: syndetic organic chemistry; medicinal chemistry; chemical biology; protein engineering; biocatalysis
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Guest Editor
Department of Drug Sciences, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy
Interests: rational design and analytical characterization by MS-based approaches of naturally and synthetically glycosylated proteins (e.g., glycoconjugate vaccines, monoclonal antibodies) and nanoparticles

Special Issue Information

Dear Colleagues,

Glycoconjugate vaccines, obtained by linking carbohydrates to protein carriers, have had a critical role in fighting infectious diseases. RNA-based technologies are a novel approach to developing anti-infection and anti-cancer vaccines from preclinical to clinical stages. They are particularly effective in targeting carbohydrates, one of the most important classes of surface antigens, and can also be used as adjuvants to promote immunostimulant effects.

While traditional conjugation approaches and using soluble proteins as carriers have been common, recent advancements have been made in the field. New glycosylation strategies have been established, and nanotechnology is increasingly used in vaccine development. Chemically glycosylated organic and inorganic nanoparticles are being used to enhance immunostimulation and delivery. Finally, the complexity of glycoconjugate structures requires suitable analytical methods to support their design and development.

We are pleased to invite you to contribute to this Special Issue, which will focus on recent advancements in the design, development, and characterization of glycosylated proteins and nanoparticles as potential vaccines. The Special Issue is open to original research articles and reviews on antigenic/immunogenic oligosaccharides or new glyco-derivatives, as well as pre-clinical and clinical studies on anti-infection or anticancer glyco-(nano)vaccines. Investigations on analytical approaches to support the design and production of glycoconjugates will also be considered.

We look forward to receiving your contributions.

Prof. Dr. Marco Terreni
Dr. Sara Tengattini
Guest Editors

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Keywords

  • glycoconjugate vaccines
  • infection diseases
  • anticancer vaccines
  • glycosylated nanovaccines
  • antigenic saccharides
  • conjugation chemistry
  • glycoconjugate characterization
  • dual-acting vaccines
  • glycosylated nanoparticles

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Published Papers (4 papers)

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Research

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16 pages, 3051 KiB  
Article
Effect of Childhood Pneumococcal Conjugate Vaccination on Invasive Disease Serotypes in Serbia
by Nataša Opavski, Miloš Jovićević, Jovana Kabić, Dušan Kekić, Ina Gajić and Study Group for Laboratory Surveillance of Invasive Pneumococcal Diseases
Vaccines 2024, 12(8), 940; https://doi.org/10.3390/vaccines12080940 - 22 Aug 2024
Cited by 3 | Viewed by 1463
Abstract
In Serbia, PCV10 was introduced into the routine immunization for children under 2 in 2018 and replaced by PCV13 in 2022. We evaluated their impact on the distribution of invasive pneumococcal disease (IPD) serotypes across all age groups. Overall, 756 isolates were obtained [...] Read more.
In Serbia, PCV10 was introduced into the routine immunization for children under 2 in 2018 and replaced by PCV13 in 2022. We evaluated their impact on the distribution of invasive pneumococcal disease (IPD) serotypes across all age groups. Overall, 756 isolates were obtained from patients with IPD between 2010 and 2023 through laboratory surveillance. In the post-vaccination period, serotypes 14, 19F, 23F, and 6A significantly declined, while 3 and 19A considerably increased. This was especially evident in the ≤2 years group, making these serotypes the most prevalent among them. Serotype 3 dominated, representing 19.1% of all invasive isolates prior to 2018 and 33.1% thereafter. While serotype coverage of PCV10 has significantly decreased in the ≤2 years group (from 74.2% before 2018 to 29.5% after 2018), PCV13 coverage was 63.9% after 2018. In the post-PCV period, non-PCV13 serotypes, such as 9N, 10A, 15A, 15B, 15C, 22F, 6C, 6D, and 7C, increased across all isolates. Antibiotic non-susceptibility considerably decreased after 2018. MLST analysis showed shifts in sequence type prevalence, with pre-PCV lineages replaced and ongoing serotype 3 persistence, alongside potential capsule-switching events. These findings emphasize a noticeable shift in the distribution of serotypes and adaptability of pneumococcal populations, highlighting the importance of ongoing surveillance and the requirement for the urgent introduction of higher valent vaccines into the National Immunization Program. Full article
(This article belongs to the Special Issue Advances in Glycoconjugate Vaccines and Nanovaccines)
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25 pages, 5943 KiB  
Article
Modeling 1-Cyano-4-Dimethylaminopyridine Tetrafluoroborate (CDAP) Chemistry to Design Glycoconjugate Vaccines with Desired Structural and Immunological Characteristics
by Rebecca Nappini, Renzo Alfini, Salvatore Durante, Laura Salvini, Maria Michelina Raso, Elena Palmieri, Roberta Di Benedetto, Martina Carducci, Omar Rossi, Paola Cescutti, Francesca Micoli and Carlo Giannelli
Vaccines 2024, 12(7), 707; https://doi.org/10.3390/vaccines12070707 - 24 Jun 2024
Cited by 3 | Viewed by 2613
Abstract
Glycoconjugation is a well-established technology for vaccine development: linkage of the polysaccharide (PS) antigen to an appropriate carrier protein overcomes the limitations of PS T-independent antigens, making them effective in infants and providing immunological memory. Glycoconjugate vaccines have been successful in reducing the [...] Read more.
Glycoconjugation is a well-established technology for vaccine development: linkage of the polysaccharide (PS) antigen to an appropriate carrier protein overcomes the limitations of PS T-independent antigens, making them effective in infants and providing immunological memory. Glycoconjugate vaccines have been successful in reducing the burden of different diseases globally. However, many pathogens still require a vaccine, and many of them display a variety of glycans on their surface that have been proposed as key antigens for the development of high-valency glycoconjugate vaccines. CDAP chemistry represents a generic conjugation strategy that is easily applied to PS with different structures. This chemistry utilizes common groups to a large range of PS and proteins, e.g., hydroxyl groups on the PS and amino groups on the protein. Here, new fast analytical tools to study CDAP reaction have been developed, and reaction conditions for PS activation and conjugation have been extensively investigated. Mathematical models have been built to identify reaction conditions to generate conjugates with wanted characteristics and successfully applied to a large number of bacterial PSs from different pathogens, e.g., Klebsiella pneumoniae, Salmonella Paratyphi A, Salmonella Enteritidis, Salmonella Typhimurium, Shighella sonnei and Shigella flexneri. Furthermore, using Salmonella Paratyphi A O-antigen and CRM197 as models, a design of experiment approach has been used to study the impact of conjugation conditions and conjugate features on immunogenicity in rabbits. The approach used can be rapidly extended to other PSs and accelerate the development of high-valency glycoconjugate vaccines. Full article
(This article belongs to the Special Issue Advances in Glycoconjugate Vaccines and Nanovaccines)
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Review

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44 pages, 2319 KiB  
Review
Recent Progress in Developing Extracellular Vesicles as Nanovehicles to Deliver Carbohydrate-Based Therapeutics and Vaccines
by Japigorn Puagsopa, Niksa Tongviseskul, Thapakorn Jaroentomeechai and Bunyarit Meksiriporn
Vaccines 2025, 13(3), 285; https://doi.org/10.3390/vaccines13030285 - 7 Mar 2025
Viewed by 1544
Abstract
Cell-derived, nanoscale extracellular vesicles (EVs) have emerged as promising tools in diagnostic, therapeutic, and vaccine applications. Their unique properties including the capability to encapsulate diverse molecular cargo as well as the versatility in surface functionalization make them ideal candidates for safe and effective [...] Read more.
Cell-derived, nanoscale extracellular vesicles (EVs) have emerged as promising tools in diagnostic, therapeutic, and vaccine applications. Their unique properties including the capability to encapsulate diverse molecular cargo as well as the versatility in surface functionalization make them ideal candidates for safe and effective vehicles to deliver a range of biomolecules including gene editing cassettes, therapeutic proteins, glycans, and glycoconjugate vaccines. In this review, we discuss recent advances in the development of EVs derived from mammalian and bacterial cells for use in a delivery of carbohydrate-based protein therapeutics and vaccines. We highlight key innovations in EVs’ molecular design, characterization, and deployment for treating diseases including Alzheimer’s disease, infectious diseases, and cancers. We discuss challenges for their clinical translation and provide perspectives for future development of EVs within biopharmaceutical research and the clinical translation landscape. Full article
(This article belongs to the Special Issue Advances in Glycoconjugate Vaccines and Nanovaccines)
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20 pages, 1890 KiB  
Review
Nanoparticles as Delivery Systems for Antigenic Saccharides: From Conjugation Chemistry to Vaccine Design
by Marie-Jeanne Archambault, Laetitia Mwadi Tshibwabwa, Mélanie Côté-Cyr, Serge Moffet, Tze Chieh Shiao and Steve Bourgault
Vaccines 2024, 12(11), 1290; https://doi.org/10.3390/vaccines12111290 - 19 Nov 2024
Cited by 1 | Viewed by 2091
Abstract
Glycoconjugate vaccines have been effective in preventing numerous bacterial infectious diseases and have shown recent potential to treat cancers through active immunotherapy. Soluble polysaccharides elicit short-lasting immune responses and are usually covalently linked to immunogenic carrier proteins to enhance the antigen-specific immune response [...] Read more.
Glycoconjugate vaccines have been effective in preventing numerous bacterial infectious diseases and have shown recent potential to treat cancers through active immunotherapy. Soluble polysaccharides elicit short-lasting immune responses and are usually covalently linked to immunogenic carrier proteins to enhance the antigen-specific immune response by stimulating T-cell-dependent mechanisms. Nonetheless, the conjugation of purified polysaccharides to carrier proteins complexifies vaccine production, and immunization with protein glycoconjugates can lead to the undesirable immunogenic interference of the carrier. Recently, the use of nanoparticles and nanoassemblies for the delivery of antigenic saccharides has gathered attention from the scientific community. Nanoparticles can be easily functionalized with a diversity of functionalities, including T-cell epitope, immunomodulator and synthetic saccharides, allowing for the modulation and polarization of the glycoantigen-specific immune response. Notably, the conjugation of glycan to nanoparticles protects the antigens from degradation and enhances their uptake by immune cells. Different types of nanoparticles, such as liposomes assembled from lipids, inorganic nanoparticles, virus-like particles and dendrimers, have been explored for glycovaccine design. The versatility of nanoparticles and their ability to induce robust immune responses make them attractive delivery platforms for antigenic saccharides. The present review aims at summarizing recent advancements in the use of nano-scaled systems for the delivery of synthetic glycoantigens. After briefly presenting the immunological mechanisms required to promote a robust immune response against antigenic saccharides, this review will offer an overview of the current trends in the nanoparticle-based delivery of glycoantigens. Full article
(This article belongs to the Special Issue Advances in Glycoconjugate Vaccines and Nanovaccines)
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