Evaluating the Immune Response to RNA Vaccine

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "DNA and mRNA Vaccines".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 1840

Special Issue Editors

Vaccine Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
Interests: mRNA vaccine; infectious disease; novel vaccine platform; adjuvant; immune mechanism

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Guest Editor
School of Pharmaceutical Sciences, Shandong University, Jinan, China
Interests: infectious disease; HBV; HCC; innate immunity; adjuvant

Special Issue Information

Dear Colleagues,

RNA technology has demonstrated numerous advantages in vaccine development and is widely recognized for its versatility. Specifically, it can be utilized in the development of new vaccines or therapeutics for various types of infectious or non-infectious diseases by manipulating the mRNA cargo and the lipid-based delivery system.

However, we still lack a comprehensive understanding of how these vaccines work, particularly regarding their interactions with the immune system and the underlying mechanism of action implicated in the generation of high-quality vaccine responses.

In this Special Issue, we seek original research articles and review articles that address the immune mechanisms of RNA vaccines. This includes, but is not limited to, innate immune signatures, the magnitude and quality of antibody responses, and the regulation of B cell and T cell compartments. These investigations provide essential guidance for the rational design of RNA vaccines.

Dr. Ang Lin
Dr. Huajun Zhao
Guest Editors

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Keywords

  • RNA vaccine
  • mechanism of action
  • immune regulation
  • innate immunity
  • adaptive vaccine response

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Published Papers (2 papers)

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10 pages, 2440 KiB  
Brief Report
Leveraging an mRNA Platform for the Development of Vaccines Against Egg Allergy
by Xianyu Shao, Lijing Liu, Changzhen Weng, Kun Guo, Zhutao Lu, Lulu Huang, Zhenhua Di, Yixuan Guo, Guorong Di, Renmei Qiao, Jingyi Wang, Yong Yang, Shiyu Sun, Shentian Zhuang and Ang Lin
Vaccines 2025, 13(5), 448; https://doi.org/10.3390/vaccines13050448 - 24 Apr 2025
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Abstract
Background: Food allergy (FA) poses a major global health issue due to the increasing prevalence and lack of effective prevention strategies. Allergen-specific immunotherapy (AIT) has emerged as a disease-modifying therapy for FA. However, due to long-term treatment duration and unexpected adverse reactions, only [...] Read more.
Background: Food allergy (FA) poses a major global health issue due to the increasing prevalence and lack of effective prevention strategies. Allergen-specific immunotherapy (AIT) has emerged as a disease-modifying therapy for FA. However, due to long-term treatment duration and unexpected adverse reactions, only a minority of patients benefit from AIT. Therefore, effective prophylactic interventions are urgently needed for FA patients. Methods: In this proof-of-concept study, using a well-established mRNA platform, we developed mRNA vaccine candidates encoding for the major egg white allergen Gal d2 and comprehensively evaluated their prophylactic efficacy against anaphylaxis in a Gal d2-induced allergic mouse model. Results: Two vaccine formulations, Gal d2 mRNA vaccine and Gal d2-IL-10 mRNA vaccine, both demonstrated potent ability in inducing allergen-specific IgG and Th1-type T cells. Importantly, the two vaccine formulations showed promise in preventing the onset of allergic disease, which is indicated by prevention of body temperature decline during anaphylaxis. Conclusions: We provided preliminary proof-of-concept evidence showing that the mRNA platform is unique and holds promise for the development of anti-allergy vaccines. This is largely attributed to the capacities of mRNA vaccines in eliciting an allergen-blocking antibody, shifting Th2 towards Th1 immunity, as well as in generating peripheral tolerance. However, further investigations are required to better understand the mode of action. Full article
(This article belongs to the Special Issue Evaluating the Immune Response to RNA Vaccine)
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12 pages, 2225 KiB  
Brief Report
Development and Evaluation of the Immunogenic Potential of an Unmodified Nucleoside mRNA Vaccine for Herpes Zoster
by Shun Zhang, Xiaojie Wang, Tongyi Zhao, Chen Yang and Lulu Huang
Vaccines 2025, 13(1), 68; https://doi.org/10.3390/vaccines13010068 - 13 Jan 2025
Viewed by 1255
Abstract
Background/Objectives: Approved mRNA vaccines commonly use sequences modified with pseudouridine to enhance translation efficiency and mRNA stability. However, this modification can result in ribosomal frameshifts, reduced immunogenicity, and higher production costs. This study aimed to explore the potential of unmodified mRNA sequences for [...] Read more.
Background/Objectives: Approved mRNA vaccines commonly use sequences modified with pseudouridine to enhance translation efficiency and mRNA stability. However, this modification can result in ribosomal frameshifts, reduced immunogenicity, and higher production costs. This study aimed to explore the potential of unmodified mRNA sequences for varicella-zoster virus (VZV) and evaluate whether codon optimization could overcome the limitations of pseudouridine modification. Methods: We utilized artificial intelligence (AI) to design several unmodified gE mRNA sequences for VZV, considering factors such as codon preference and secondary structure. The optimized mRNA sequences were assessed for protein expression levels in vitro and were subsequently used to develop a vaccine, named Vac07, encapsulated in a lipid nanoparticle (LNP) delivery system. The immunogenicity of Vac07 was evaluated in mice. Results: Codon-optimized mRNA sequences showed significantly higher protein expression levels in vitro compared to wild-type (WT) sequences. Vaccination with Vac07 demonstrated immunogenicity in mice that was comparable to, or even superior to, the licensed Shingrix vaccine, characterized by a stronger Th1-biased antibody response and a slightly more robust Th1-type cellular response. Conclusions: Codon-optimized unmodified mRNA sequences may also represent a viable approach for mRNA vaccine development. These optimized sequences have the potential to lower production costs while possibly enhancing the immunogenicity of mRNA vaccines. Vac07, developed using this method, shows promise as a potentially more efficient and cost-effective mRNA vaccine candidate for VZV. Full article
(This article belongs to the Special Issue Evaluating the Immune Response to RNA Vaccine)
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