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Novel Vaccines and Vaccine Technologies for Emerging Infections

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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 18664

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Special Issue Editors

Prof. Dr. Wangxue Chen

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Guest Editor

Human Health and Therapeutics Research Center (HHT), National Research Council Canada, Ottawa, ON, Canada
Interests: antimicrobial resistance; phage therapy; host–pathogen interaction; vaccines; alternatives to antibiotics
Special Issues, Collections and Topics in MDPI journals

Dr. Xuguang Li

E-Mail Website
Guest Editor

Centre for Biologics Evaluation, Biologics and Radiopharmaceutical Drug Directorate, Health Products and Food Branch (HPFB), Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON K1A 0K9, Canada
Interests: immunity

Prof. Dr. Amine A. Kamen

E-Mail Website
Guest Editor

Department of Bioengineering, McGill University, Montreal, QC H2X 1Y4, Canada
Interests: cell culture engineering; bioprocess optimization and scale-up; process analytical technologies and process control; viral vaccines manufacturing; viral vectors and nanoparticules for gene delivery and vaccination
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vaccines are one of the most effective medical inventions in modern history and have saved hundreds of millions of lives so far. The rapid development and deployment of vaccines in response to the COVID-19 pandemic have showcased the unprecedented success of vaccines in global public health, security, and prosperity. Vaccination is highly cost-effective in preventing microbial infection and halting its transmission, and also plays a critical role in the efforts to reduce antimicrobial use.

The tremendous global political enthusiasm, research efforts, and financial investment in vaccine development during the COVID-19 pandemic response lead to significant advances in many aspects of vaccine R&D, including novel vaccine platforms and technologies, the rapid development and production of vaccines, and the renewed recognition of the importance of mucosal immunity and vaccination. These advances are likely to accelerate vaccine development and production for future responses to pandemics and emerging infections.

This Special Issue aims to provide a platform for sharing the most recent advances in the development of novel vaccine candidates, platforms, and technologies for combating emerging infections and future pandemics. More specifically, we welcome the contribution of original research articles, reviews, and commentaries that address the following topics:

New vaccine platforms, technologies, and adjuvants;
Universal vaccine candidates;
Mucosal vaccines and vaccination;
Modular vaccine platforms for rapid biomanufacturing and expedited regulatory approval;
Vaccines as a tool for antimicrobial resistance;
AI application in the rapid identification of novel vaccine antigens;
Immune correlates of vaccine-induced protection;
Systems immunology and vaccinology;
Novel in vitro and in vivo assays and models for assessing vaccine-induced immunity and predicting vaccine efficacies;
Vaccine bioprocess and manufactures.

Prof. Dr. Wangxue Chen
Dr. Xuguang Li
Prof. Dr. Amine A. Kamen
Guest Editors

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

novel vaccines and adjuvant
universal vaccines
mucosal vaccines
emerging infections
antimicrobial resistance
systems vaccinology
vaccine production

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Published Papers (8 papers)

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Research

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15 pages, 1609 KB

Open AccessArticle

Advancing Reversed-Phase Chromatography Analytics of Influenza Vaccines Using Machine Learning Approaches on a Diverse Range of Antigens and Formulations

by Barry Lorbetskie, Narges Manouchehri, Michel Girard, Simon Sauvé and Huixin Lu

Vaccines 2025, 13(8), 820; https://doi.org/10.3390/vaccines13080820 - 31 Jul 2025

Viewed by 395

Abstract

One concern in the yearly re-formulation of influenza vaccines is the time-consuming manufacturing of vaccine potency reagents, particularly for emergency responses. The continuous evaluation of modern techniques such as reversed-phase (RP) chromatography is an asset for streamlining this process. One challenge with RP methods, however, is the need to re-optimize methods for antigens that show poor separation, which can be highly dependent on analyst experience and available data. In this study, we leveraged a large RP dataset of influenza antigens to explore machine learning (ML) approaches of classifying challenging separations for computer-assisted method re-optimization across years, products, and analysts. Methods: To address recurring chromatographic issues—such as poor resolution, strain co-elution, and signal absence—we applied data augmentation techniques to correct class imbalance and trained multiple supervised ML classifiers to distinguish between these peak profiles. Results: With data augmentation, several ML models demonstrated promising accuracy in classifying chromatographic profiles according to the provided labels. These models effectively distinguished patterns indicative of separation issues in real-world data. Conclusions Our findings highlight the potential of ML as a computer assisted tool in the evaluation of vaccine quality, offering a scalable and objective approach to chromatogram classification. By reducing reliance on manual interpretation, ML can expedite the optimization of analytical methods, which is particularly needed for rapid responses. Future research involving larger, inter-laboratory datasets will further elucidate the utility of ML in vaccine analysis. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

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21 pages, 3103 KB

Open AccessArticle

Systemic and Mucosal Humoral Immune Responses to Lumazine Synthase 60-mer Nanoparticle SARS-CoV-2 Vaccines

by Cheng Cheng, Jeffrey C. Boyington, Edward K. Sarfo, Cuiping Liu, Danealle K. Parchment, Andrea Biju, Angela R. Corrigan, Lingshu Wang, Wei Shi, Yi Zhang, Yaroslav Tsybovsky, Tyler Stephens, Adam S. Olia, Audrey S. Carson, Syed M. Moin, Eun Sung Yang, Baoshan Zhang, Wing-Pui Kong, Peter D. Kwong, John R. Mascola and Theodore C. Pierson Show full author list Hide full author list

Vaccines 2025, 13(8), 780; https://doi.org/10.3390/vaccines13080780 - 23 Jul 2025

Viewed by 771

Abstract

Background: Vaccines that stimulate systemic and mucosal immunity to a level required to prevent SARS-CoV-2 infection and transmission are an unmet need. Highly protective hepatitis B and human papillomavirus nanoparticle vaccines highlight the potential of multivalent nanoparticle vaccine platforms to provide enhanced immunity. Here, we report the construction and characterization of self-assembling 60-subunit icosahedral nanoparticle SARS-CoV-2 vaccines using the bacterial enzyme lumazine synthase (LuS). Methods and Results: Nanoparticles displaying prefusion-stabilized SARS-CoV-2 spike ectodomains fused to the surface-exposed amino terminus of LuS were designed using structure-guided approaches. Negative stain-electron microscopy studies of purified nanoparticles were consistent with self assembly into 60-mer nanoparticles displaying 20 spike trimers. After two intramuscular doses, these purified spike-LuS nanoparticles elicited significantly higher SARS-CoV-2 neutralizing activity than spike trimers in vaccinated mice. Furthermore, intramuscular DNA priming and intranasal boosting with a SARS-CoV-2 LuS nanoparticle vaccine stimulated mucosal IgA responses. Conclusion: These data identify LuS nanoparticles as highly immunogenic SARS-CoV-2 vaccine candidates and support the further development of this platform against SARS-CoV-2 and its emerging variants. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

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14 pages, 1435 KB

Open AccessArticle

Epigenetic Drift Is Involved in the Efficacy of HBV Vaccination

by Francesca Ferraresi, Simona Anticoli, Stefano Salvioli, Chiara Pirazzini, Luciano Calzari, Davide Gentilini, Christian Albano, Reparata Rosa Di Prinzio, Salvatore Zaffina, Rita Carsetti, Paolo Garagnani, Anna Ruggieri and Katarzyna Malgorzata Kwiatkowska

Vaccines 2024, 12(12), 1330; https://doi.org/10.3390/vaccines12121330 - 27 Nov 2024

Viewed by 1551

Abstract

Background/Objectives: HBV infections can lead to serious liver complications that can have fatal consequences. In 2022, around 1.1 million individuals died from HBV-related cirrhosis and hepatocellular carcinoma. Vaccines allow us to save more than 2.5 million lives each year; however, up to 10% of vaccinated individuals may not develop sufficient protective antibody levels. The aim of this study was to investigate the epigenetic drift in the response to HBV vaccine in isolated B cells. Methods: Epigenetic drift was measured by counting rare DNA methylation variants. These epivariants were detected in epigenome-wide data collected from isolated B cell samples from 41 responders and 30 non-responders (age range 22–62 years) to vaccination against HBV. Results: We found an accumulation of epivariants in the NR group, with a significant increase in hyper-methylated aberrations. We identified the chromosomes (1, 3, 11, 12, and 14) and genes (e.g., RUSC1_AS1 or TROVE2) particularly enriched in epivariants in NRs. The literature search and pathway analysis indicate that such genes are involved in the correct functioning of the immune system. Moreover, we observed a correlation between epigenetic drift and DNA methylation entropy in the male population of the cohort. Finally, we confirmed the correlation between epivariant loads and age-related epigenetic clocks. Conclusions: Our findings support the idea that an age-related derangement of the epigenetic architecture is involved in unresponsiveness to the HBV vaccine. Furthermore, the overall results highlight the interconnection between various epigenetic dynamics (such as drift, clocks, and entropy), although these interconnections seem not to be involved in the altered immunological activity. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

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14 pages, 2970 KB

Open AccessArticle

Development of Long-Term Stability of Enveloped rVSV Viral Vector Expressing SARS-CoV-2 Antigen Using a DOE-Guided Approach

by MD Faizul Hussain Khan, Caroline E. Wagner and Amine A. Kamen

Vaccines 2024, 12(11), 1240; https://doi.org/10.3390/vaccines12111240 - 30 Oct 2024

Cited by 1 | Viewed by 2334

Abstract

Liquid formulations have been successfully used in many viral vector vaccines including influenza (Flu), hepatitis B, polio (IPV), Ebola, and COVID-19 vaccines. The main advantage of liquid formulations over lyophilized formulations is that they are cost-effective, as well as easier to manufacture and distribute. However, studies have shown that the liquid formulations of enveloped viral vector vaccines are not stable over extended periods of time. In this study, we explored the development of the liquid formulations of an enveloped recombinant Vesicular Stomatitis Virus (VSV) expressing the SARS-CoV-2 spike glycoprotein. To do so, we used a design of experiments (DOE) method, which allowed us to assess the stability dynamics of the viral vector in an effective manner. An initial stability study showed that trehalose, gelatin, and histidine were effective at maintaining functional viral titers during freeze–thaw stress and at different temperatures (−20, 4, 20, and 37 °C). These preliminary data helped to identify critical factors for the subsequent implementation of the DOE method that incorporated a stress condition at 37 °C. We used the DOE results to identify the optimal liquid formulations under the selected accelerated stress conditions, which then guided the identification of long-term storage conditions for further evaluation. In the long-term stability study, we identified several liquid formulations made of sugar (sucrose, trehalose, and sorbitol), gelatin, and a histidine buffer that resulted in the improved stability of rVSV-SARS-CoV-2 at 4 °C for six months. This study highlights an effective approach for the development of liquid formulations for viral vector vaccines, contributing significantly to the existing knowledge on enveloped viral vector thermostability. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

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15 pages, 4547 KB

Open AccessArticle

Optimization of Culture Media and Feeding Strategy for High Titer Production of an Adenoviral Vector in HEK 293 Fed-Batch Culture

by Chun Fang Shen, Anja Rodenbrock, Stephane Lanthier, Elodie Burney and Martin Loignon

Vaccines 2024, 12(5), 524; https://doi.org/10.3390/vaccines12050524 - 10 May 2024

Cited by 1 | Viewed by 3004

Abstract

Adenoviruses are efficient and safe vectors for delivering target antigens and adenovirus-based vaccines have been used against a wide variety of pathogens, including tuberculosis and COVID-19. Cost-effective and scalable biomanufacturing processes are critical for the commercialization of adenovirus-vectored vaccines. Adenoviral vectors are commonly produced through the infection of batch cultures at low cell density cultures, mostly because infections at high cell densities result in reduced cell-specific virus productivity and does not improve volumetric productivity. In this study, we have investigated the feasibility of improving the volumetric productivity by infecting fed-batch cultures at high cell densities. Four commercial and one in-house developed serum-free media were first tested for supporting growth of HEK 293 cells and production of adenovirus type 5 (Ad5) in batch culture. Two best media were then selected for development of fed-batch culture to improve cell growth and virus productivity. A maximum viable cell density up to 16 × 10⁶ cells/mL was achieved in shake flask fed-batch cultures using the selected media and commercial or in-house developed feeds. The volumetric virus productivity was improved by up to six folds, reaching 3.0 × 10¹⁰ total viral particles/mL in the fed-batch culture cultivated with the media and feeds developed in house and infected at a cell density of 5 × 10⁶ cells/mL. Additional rounds of optimization of media and feed were required to maintain the improved titer when the fed-batch culture was scaled up in a bench scale (3 L) bioreactor. Overall, the results suggested that fed-batch culture is a simple and feasible process to significantly improve the volumetric productivity of Ad5 through optimization and balance of nutrients in culture media and feeds. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

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Review

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23 pages, 1964 KB

Open AccessReview

Freeze-Drying of mRNA-LNPs Vaccines: A Review

by MD Faizul Hussain Khan, Floriane Baudin, Ayyappasamy Sudalaiyadum Perumal and Amine A. Kamen

Vaccines 2025, 13(8), 853; https://doi.org/10.3390/vaccines13080853 - 12 Aug 2025

Viewed by 1267

Abstract

The instability of mRNA vaccines presents significant challenges for their storage, transportation, and large-scale distribution, particularly in resource-limited countries. Recently, freeze-drying (lyophilization) has been considered as a promising approach for preserving mRNA vaccine efficacy. This formulation technique enhances the long-term stability of mRNA vaccines by converting them into a stable dry powder. The purpose of this review is to provide an overview of the current knowledge on the progress of freeze-drying techniques for mRNA vaccines, with emphasis on the associated challenges. This review highlights the factors influencing the stability of freeze-dried mRNA vaccines and provides a comprehensive overview of the formulation components, including excipients, buffers, and surfactants, as well as the process parameters and storage conditions that aim to improve stability and shelf-life. By providing these insights, this review supports the advancement of more robust, scalable, and efficient lyophilization protocols, ultimately addressing the stability limitations of mRNA vaccines and enhancing their global accessibility. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

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27 pages, 2692 KB

Open AccessReview

Leveraging Electron Beam (eBeam) Technology for Advancing the Development of Inactivated Vaccines

by Ruvindu Perera, Suresh D. Pillai, Adnan Alrubaye and Palmy Jesudhasan

Vaccines 2025, 13(2), 179; https://doi.org/10.3390/vaccines13020179 - 13 Feb 2025

Viewed by 1624

Abstract

This review provides an overview of electron beam (eBeam) technology and its applications across a wide variety of disciplines. More importantly, it discusses this technology’s advantages and its benefits in developing inactivated vaccines. eBeam technology is currently being used all around the world for a variety of industrial applications, extending from food pasteurization to the cross-linking of polymers in the wire and cable industries. It is a successful emerging alternative for developing vaccines against bacterial, protozoan, and viral pathogens. This review includes a descriptive account of the mechanism of action of eBeam and how this technology achieves the complete inactivation of pathogens while retaining the integrity of their surface epitopes. This unique advantage is crucial for the production of efficacious vaccines. This review provides a detailed account of the usage of eBeam technology for developing vaccines to protect a multitude of hosts against a wide range of pathogens. eBeam-inactivated vaccines are advantageous over live vaccines, RNA/subunit vaccines, and chemically inactivated vaccines mainly due to the complete inactivation of pathogens, and the presence of intact, highly antigenic epitopes. To conclude, this article descriptively highlights eBeam technology’s advantages over other means of vaccine development. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

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21 pages, 609 KB

Open AccessReview

ASIA Syndrome: State-of-the-Art and Future Perspectives

by Mario Caldarelli, Pierluigi Rio, Vincenzo Giambra, Antonio Gasbarrini, Giovanni Gambassi and Rossella Cianci

Vaccines 2024, 12(10), 1183; https://doi.org/10.3390/vaccines12101183 - 17 Oct 2024

Cited by 3 | Viewed by 6081

Abstract

The expression “Autoimmune/inflammatory syndrome induced by adjuvants (ASIA)” was coined by Shoenfeld and colleagues in 2011. It defines a group of immune-mediated disorders that arise in people, with a genetic predisposition, following exposure to adjuvant agents. This syndrome has been reported after contact with silicone implants, medications, infections, metals, vaccines, and other substances. It typically occurs in individuals with a genetic predisposition, particularly involving genes, such as HLA-DRB1 (major histocompatibility complex, class II, DR beta 1) and PTPN22 (protein tyrosine phosphatase non-receptor type 22). Some stimuli lead to an overactivation of the immune system, prompt the production of autoantibodies, and finally cause autoimmune disorders. This narrative review aims to provide an overview of the ASIA syndrome with a special focus on the role of adjuvants in different vaccines, especially after the COVID-19 pandemic, and insights into development of new treatments. Full article

(This article belongs to the Special Issue Novel Vaccines and Vaccine Technologies for Emerging Infections)

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