Biotechnologies Applied in Vaccine Research

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: 31 August 2025 | Viewed by 16787

Special Issue Editor


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Guest Editor
Department of Nursing and Department of Medical Technology, Jenteh Junior College of Medicine, Nursing and Management, Miaoli County 35664, Taiwan
Interests: biopharmaceuticals; vaccine; biotechnology; nanotechnology; microbiology; bacteriology; virology
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Special Issue Information

Dear Colleagues,

Traditional vaccines can be classified as inactivated vaccines, live attenuated vaccines, and subunit vaccines given orally, via intramuscular (IM) injection, and via subcutaneous (SC) injection. Recently, recombinant protein vaccines, DNA vaccines, mRNA vaccines, and multiple/alternative administration route vaccines have been developed for human use to make vaccines more secure and effective. These vaccine platforms have been developed using various biotechnologies, such as adenovirus vectors, nanoparticles, mRNA, recombination DNA, and other vaccine delivery systems.

In this Special Issue, we are inviting contributions related to advances in biotechnologies applied in vaccine research. It will explore the biotechnologies applied in the development of vaccine research and platforms. We welcome original research articles and reviews. Research areas may include vaccines, biotechnology, vaccine vectors, DNA, mRNA, subunits, novel adjuvants, and delivery systems. We look forward to receiving your contributions.

Dr. Yuan-Chuan Chen
Guest Editor

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Keywords

  • vaccine
  • biotechnology
  • vector
  • nanoparticle
  • virus
  • bacteria
  • recombination DNA
  • mRNA
  • subunit
  • adjuvant
  • delivery

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Published Papers (5 papers)

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Research

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14 pages, 3270 KiB  
Article
Effective Immune Protection of Mice from Murine Cytomegalovirus Infection by Oral Salmonella-Based Vaccine Expressing Viral M78 Antigen
by Yujun Liu, Hao Gong, Jiaming Zhu and Fenyong Liu
Vaccines 2025, 13(2), 137; https://doi.org/10.3390/vaccines13020137 - 28 Jan 2025
Cited by 1 | Viewed by 792
Abstract
Background: Human cytomegalovirus (CMV) is the most common cause of viral congenital infections worldwide. The development of effective vaccines against human CMV infection and disease is a high priority. Attenuated Salmonella are attractive oral vaccine vectors against human diseases because they can [...] Read more.
Background: Human cytomegalovirus (CMV) is the most common cause of viral congenital infections worldwide. The development of effective vaccines against human CMV infection and disease is a high priority. Attenuated Salmonella are attractive oral vaccine vectors against human diseases because they can be administrated orally. Methods: In this study, an attenuated Salmonella strain was generated as an oral vaccine vector for the delivery and expression of the M78 protein of murine cytomegalovirus (MCMV). Using the MCMV infection of mice as the CMV infection model, we characterized the immune responses and protection induced by the constructed Salmonella-based vaccine. Results: The generated Salmonella-based vaccine, v-M78, which contained an M78 expression plasmid construct, carried out gene transfer efficiently for M78 expression and showed little pathogenicity and virulence in mice. In orally vaccinated mice, v-M78 induced anti-MCMV serum IgG and mucosal IgA responses and also elicited anti-MCMV T cell responses. Furthermore, mice immunized with v-M78 were protected from intraperitoneal and intranasal challenges with MCMV. The v-M78 vaccination reduced the titers of the challenged viruses in spleens, livers, lungs, and salivary glands. Conclusions: These results provide the first direct evidence that a Salmonella-based vaccine expressing M78 elicits strong humoral and cellular immune responses and induces immune protection against MCMV infection. Furthermore, our study demonstrates the potential of using Salmonella-based oral vaccines against CMV infection. Full article
(This article belongs to the Special Issue Biotechnologies Applied in Vaccine Research)
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21 pages, 4144 KiB  
Article
Development of a Cationic Polymeric Micellar Structure with Endosomal Escape Capability Enables Enhanced Intramuscular Transfection of mRNA-LNPs
by Siyuan Deng, Han Shao, Hongtao Shang, Lingjin Pang, Xiaomeng Chen, Jingyi Cao, Yi Wang and Zhao Zhao
Vaccines 2025, 13(1), 25; https://doi.org/10.3390/vaccines13010025 - 30 Dec 2024
Viewed by 1288
Abstract
Background/Objectives: The endosomal escape of lipid nanoparticles (LNPs) is crucial for efficient mRNA-based therapeutics. Here, we present a cationic polymeric micelle (cPM) as a safe and potent co-delivery system with enhanced endosomal escape capabilities. Methods: We synthesized a cationic and ampholytic di-block copolymer, [...] Read more.
Background/Objectives: The endosomal escape of lipid nanoparticles (LNPs) is crucial for efficient mRNA-based therapeutics. Here, we present a cationic polymeric micelle (cPM) as a safe and potent co-delivery system with enhanced endosomal escape capabilities. Methods: We synthesized a cationic and ampholytic di-block copolymer, poly (poly (ethylene glycol)4-5 methacrylatea-co-hexyl methacrylateb)X-b-poly(butyl methacrylatec-co-dimethylaminoethyl methacrylated-co-propyl acrylatee)Y (p(PEG4-5MAa-co-HMAb)X-b-p(BMAc-co-DMAEMAd-co-PAAe)Y), via reversible addition–fragmentation chain transfer polymerization. The cPMs were then formulated using the synthesized polymer by the dispersion–diffusion method and characterized by dynamic light scattering (DLS) and cryo-transmission electron microscopy (CryoTEM). The membrane-destabilization activity of the cPMs was evaluated by a hemolysis assay. We performed an in vivo functional assay of firefly luciferase (Fluc) mRNA using two of the most commonly studied LNPs, SM102 LNP and Dlin-MC3-DMA LNPs. Results: With a particle size of 61.31 ± 0.68 nm and a zeta potential of 37.76 ± 2.18 mV, the cPMs exhibited a 2–3 times higher firefly luciferase signal at the injection site compared to the control groups without cPMs following intramuscular injection in mice, indicating the high potential of cPMs to enhance the endosomal escape efficiency of mRNA-LNPs. Conclusions: The developed cPM, with enhanced endosomal escape capabilities, presents a promising strategy to improve the expression efficiency of delivered mRNAs. This approach offers a novel alternative strategy with no modifications to the inherent properties of mRNA-LNPs, preventing any unforeseeable changes in formulation characteristics. Consequently, this polymer-based nanomaterial holds immense potential for clinical applications in mRNA-based vaccines. Full article
(This article belongs to the Special Issue Biotechnologies Applied in Vaccine Research)
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15 pages, 1201 KiB  
Article
Evaluation of the Efficacy of the Vaccine Production Process in Removing Residual Host Cell DNA from the Vero Cell Rabies Vaccine
by Jia Li, Ruowen Pan, Fengyi Yue, Tie Gao, Xiaohong Wu, Leitai Shi, Yunpeng Wang, Danhua Zhao, Zhaohui Lan, Hongxu Chen, Qiang Ye and Shouchun Cao
Vaccines 2024, 12(12), 1379; https://doi.org/10.3390/vaccines12121379 - 6 Dec 2024
Cited by 1 | Viewed by 1386
Abstract
Background: The Vero cell rabies vaccine is currently the most widely used human rabies vaccine. However, owing to the presence of residual host cell DNA (HCD) in the final product and the potential tumorigenicity of the DNA of high-passage Vero cells, the WHO [...] Read more.
Background: The Vero cell rabies vaccine is currently the most widely used human rabies vaccine. However, owing to the presence of residual host cell DNA (HCD) in the final product and the potential tumorigenicity of the DNA of high-passage Vero cells, the WHO not only sets a limit on the number of times cells used in production can be passaged, but also imposes strict requirements on the amount of residual HCD in the final vaccine product. Objectives: To systematically reduce the HCD level in the final vaccine product, multiple purification steps are included in the vaccine production process. This study investigated the effectiveness of key production steps in antigen recovery and DNA removal. Methods: The residual HCD fragment content and size distribution were detected using fluorescence quantitative PCR (qPCR) and capillary gel electrophoresis (CGE), and the rabies virus glycoprotein antigen content was detected using enzyme-linked immunosorbent assay (ELISA). The antigen recovery rate and HCD removal rate in each key process were calculated to evaluate the scientific basis and effectiveness of each production step. Additionally, the stability of the process was studied using multiple commercial batches of the product. Results: The results revealed that the total antigen recovery rate in the production process described in this report was no less than 8.5%, and the effective removal rate of residual HCD was not lower than 99.99%. Moreover, the amount of residual HCD in the final product was far below the quality standard of 2 ng/dose, and most of the residual HCD fragments were smaller than 200 bp. The results of the process stability studies on multiple commercial batches showed that the bulk human rabies vaccine produced by this process had excellent safety and efficacy and that the production process was stable and thus suitable for large-scale batch production. Conclusions: The production process described in this study achieved effective recovery of viral antigens and efficient removal of residual HCD, and the process was stable and controllable, enabling the continuous and stable production of vaccine products that meet WHO recommendations and the relevant requirements of the current edition of the Chinese Pharmacopeia. In addition, this study provides theoretical guidance for optimizing the vaccine production process. Full article
(This article belongs to the Special Issue Biotechnologies Applied in Vaccine Research)
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Review

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20 pages, 4599 KiB  
Review
Recent Advances in Lipid Nanoparticles and Their Safety Concerns for mRNA Delivery
by Jialiang Wang, Yaopeng Ding, Kellie Chong, Meng Cui, Zeyu Cao, Chenjue Tang, Zhen Tian, Yuping Hu, Yu Zhao and Shaoyi Jiang
Vaccines 2024, 12(10), 1148; https://doi.org/10.3390/vaccines12101148 - 8 Oct 2024
Cited by 14 | Viewed by 8744
Abstract
Introduction: The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances in Therapeutic LNPs: LNPs, composed of ionizable lipids, phospholipids, cholesterol, and [...] Read more.
Introduction: The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances in Therapeutic LNPs: LNPs, composed of ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, facilitate efficient cellular uptake and cytosolic release of mRNA while mitigating degradation by nucleases. However, as synthetic entities, LNPs face challenges that alter their therapeutic efficacy and safety concerns. Toxicity/Reactogenicity/Immunogenicity: This review provides a comprehensive overview of the latest advancements in LNP research, focusing on preclinical safety assessments encompassing toxicity, reactogenicity, and immunogenicity. Summary and Outlook: Additionally, it outlines potential strategies for addressing these challenges and offers insights into future research directions for enhancing the application of LNPs in mRNA therapeutics. Full article
(This article belongs to the Special Issue Biotechnologies Applied in Vaccine Research)
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21 pages, 975 KiB  
Review
Novel Administration Routes, Delivery Vectors, and Application of Vaccines Based on Biotechnologies: A Review
by Chung-I Rai, Tsu-Hsiang Kuo and Yuan-Chuan Chen
Vaccines 2024, 12(9), 1002; https://doi.org/10.3390/vaccines12091002 - 1 Sep 2024
Cited by 2 | Viewed by 3629
Abstract
Traditional vaccines can be classified into inactivated vaccines, live attenuated vaccines, and subunit vaccines given orally or via intramuscular (IM) injection or subcutaneous (SC) injection for the prevention of infectious diseases. Recently, recombinant protein vaccines, DNA vaccines, mRNA vaccines, and multiple/alternative administering route [...] Read more.
Traditional vaccines can be classified into inactivated vaccines, live attenuated vaccines, and subunit vaccines given orally or via intramuscular (IM) injection or subcutaneous (SC) injection for the prevention of infectious diseases. Recently, recombinant protein vaccines, DNA vaccines, mRNA vaccines, and multiple/alternative administering route vaccines (e.g., microneedle or inhalation) have been developed to make vaccines more secure, effective, tolerable, and universal for the public. In addition to preventing infectious diseases, novel vaccines have currently been developed or are being developed to prevent or cure noninfectious diseases, including cancer. These vaccine platforms have been developed using various biotechnologies such as viral vectors, nanoparticles, mRNA, recombination DNA, subunit, novel adjuvants, and other vaccine delivery systems. In this review, we will explore the development of novel vaccines applying biotechnologies, such as vaccines based on novel administration routes, vaccines based on novel vectors, including viruses and nanoparticles, vaccines applied for cancer prevention, and therapeutic vaccines. Full article
(This article belongs to the Special Issue Biotechnologies Applied in Vaccine Research)
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