Special Issue "The Past, Present, and Future of mRNA Vaccines"

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cellular/Molecular Immunology".

Deadline for manuscript submissions: closed (1 January 2021) | Viewed by 103090

Special Issue Editor

Prof. Dr. Norbert Pardi
E-Mail Website
Guest Editor
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Interests: mRNA vaccines targeting infectious diseases and cancer, therapy with mRNA-encoded monoclonal antibodies, gene therapy with mRNA

Special Issue Information

Dear Colleagues,

Vaccines represent one of the most successful interventions of modern medicine. Currently used vaccine types have many shortfalls, and, thus, the development of next-generation vaccines that are safe, easy-to-produce, and offer broad and durable protection against a wide range of pathogens and have the ability to eliminate various types of cancer is urgently needed. mRNA vaccines have the potential to meet these criteria and, thus, represent one of the most promising new generation vaccine modalities.

This Special Issue of Vaccines will provide a series of peer-reviewed perspective and review articles that discuss the current standing and speculate on the future of the field of mRNA vaccines. This Special Issue will discuss a broad range of topics including recent developments in various types of infectious disease and cancer mRNA vaccines, passive immunization with mRNA, delivery materials, and production of mRNA vaccines, among other topics.

Keywords

  • mRNA vaccines
  • nucleoside modification
  • Flaviviruses
  • Cancer
  • HIV-1
  • SARS-CoV-2

Published Papers (12 papers)

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Editorial

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Editorial
mRNA Innovates the Vaccine Field
Vaccines 2021, 9(5), 486; https://doi.org/10.3390/vaccines9050486 - 11 May 2021
Cited by 5 | Viewed by 1311
Abstract
Development of new vaccine modalities is a critical need to address many of the shortcomings of traditional platforms such as the lack of sufficient efficacy against certain pathogens or cancer; difficulties with production; or, in some cases, safety issues [...] Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)

Research

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Article
Development of mRNA Vaccines: Scientific and Regulatory Issues
Vaccines 2021, 9(2), 81; https://doi.org/10.3390/vaccines9020081 - 23 Jan 2021
Cited by 20 | Viewed by 8834
Abstract
The global research and development of mRNA vaccines have been prodigious over the past decade, and the work in this field has been stimulated by the urgent need for rapid development of vaccines in response to an emergent disease such as the current [...] Read more.
The global research and development of mRNA vaccines have been prodigious over the past decade, and the work in this field has been stimulated by the urgent need for rapid development of vaccines in response to an emergent disease such as the current COVID-19 pandemic. Nevertheless, there remain gaps in our understanding of the mechanism of action of mRNA vaccines, as well as their long-term performance in areas such as safety and efficacy. This paper reviews the technologies and processes used for developing mRNA prophylactic vaccines, the current status of vaccine development, and discusses the immune responses induced by mRNA vaccines. It also discusses important issues with regard to the evaluation of mRNA vaccines from regulatory perspectives. Setting global norms and standards for biologicals including vaccines to assure their quality, safety and efficacy has been a WHO mandate and a core function for more than 70 years. New initiatives are ongoing at WHO to arrive at a broad consensus to formulate international guidance on the manufacture and quality control, as well as nonclinical and clinical evaluation of mRNA vaccines, which is deemed necessary to facilitate international convergence of manufacturing and regulatory practices and provide support to National Regulatory Authorities in WHO member states. Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)
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Article
Resources, Production Scales and Time Required for Producing RNA Vaccines for the Global Pandemic Demand
Vaccines 2021, 9(1), 3; https://doi.org/10.3390/vaccines9010003 - 23 Dec 2020
Cited by 33 | Viewed by 10386 | Correction
Abstract
To overcome pandemics, such as COVID-19, vaccines are urgently needed at very high volumes. Here we assess the techno-economic feasibility of producing RNA vaccines for the demand associated with a global vaccination campaign. Production process performance is assessed for three messenger RNA (mRNA) [...] Read more.
To overcome pandemics, such as COVID-19, vaccines are urgently needed at very high volumes. Here we assess the techno-economic feasibility of producing RNA vaccines for the demand associated with a global vaccination campaign. Production process performance is assessed for three messenger RNA (mRNA) and one self-amplifying RNA (saRNA) vaccines, all currently under clinical development, as well as for a hypothetical next-generation saRNA vaccine. The impact of key process design and operation uncertainties on the performance of the production process was assessed. The RNA vaccine drug substance (DS) production rates, volumes and costs are mostly impacted by the RNA amount per vaccine dose and to a lesser extent by the scale and titre in the production process. The resources, production scale and speed required to meet global demand vary substantially in function of the RNA amount per dose. For lower dose saRNA vaccines, global demand can be met using a production process at a scale of below 10 L bioreactor working volume. Consequently, these small-scale processes require a low amount of resources to set up and operate. RNA DS production can be faster than fill-to-finish into multidose vials; hence the latter may constitute a bottleneck. Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)
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Review

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Review
mRNA Vaccines against Flaviviruses
Vaccines 2021, 9(2), 148; https://doi.org/10.3390/vaccines9020148 - 12 Feb 2021
Cited by 9 | Viewed by 2412
Abstract
Numerous vaccines have now been developed using the mRNA platform. In this approach, mRNA coding for a viral antigen is in vitro synthesized and injected into the host leading to exogenous protein expression and robust immune responses. Vaccines can be rapidly developed utilizing [...] Read more.
Numerous vaccines have now been developed using the mRNA platform. In this approach, mRNA coding for a viral antigen is in vitro synthesized and injected into the host leading to exogenous protein expression and robust immune responses. Vaccines can be rapidly developed utilizing the mRNA platform in the face of emerging pandemics. Additionally, the mRNA coding region can be easily manipulated to test novel hypotheses in order to combat viral infections which have remained refractory to traditional vaccine approaches. Flaviviruses are a diverse family of viruses that cause widespread disease and have pandemic potential. In this review, we discuss the mRNA vaccines which have been developed against diverse flaviviruses. Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)
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Review
SARS-CoV-2 mRNA Vaccines: Immunological Mechanism and Beyond
Vaccines 2021, 9(2), 147; https://doi.org/10.3390/vaccines9020147 - 12 Feb 2021
Cited by 77 | Viewed by 15856
Abstract
To successfully protect against pathogen infection, a vaccine must elicit efficient adaptive immunity, including B and T cell responses. While B cell responses are key, as they can mediate antibody-dependent protection, T cells can modulate B cell activity and directly contribute to the [...] Read more.
To successfully protect against pathogen infection, a vaccine must elicit efficient adaptive immunity, including B and T cell responses. While B cell responses are key, as they can mediate antibody-dependent protection, T cells can modulate B cell activity and directly contribute to the elimination of pathogen-infected cells. In the unprecedented race to develop an effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the respiratory disease coronavirus disease 2019 (COVID-19), messenger RNA (mRNA) vaccines have emerged as front runners thanks to their capacity for rapid development and ability to drive potent adaptive immune responses. In this review article, we provide an overview of the results from pre-clinical studies in animal models as well as clinical studies in humans that assessed the efficacy of SARS-CoV-2 mRNA vaccines, with a primary focus on adaptive immune responses post vaccination. Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)
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Review
HIV mRNA Vaccines—Progress and Future Paths
Vaccines 2021, 9(2), 134; https://doi.org/10.3390/vaccines9020134 - 07 Feb 2021
Cited by 16 | Viewed by 6185
Abstract
The SARS-CoV-2 pandemic introduced the world to a new type of vaccine based on mRNA encapsulated in lipid nanoparticles (LNPs). Instead of delivering antigenic proteins directly, an mRNA-based vaccine relies on the host’s cells to manufacture protein immunogens which, in turn, are targets [...] Read more.
The SARS-CoV-2 pandemic introduced the world to a new type of vaccine based on mRNA encapsulated in lipid nanoparticles (LNPs). Instead of delivering antigenic proteins directly, an mRNA-based vaccine relies on the host’s cells to manufacture protein immunogens which, in turn, are targets for antibody and cytotoxic T cell responses. mRNA-based vaccines have been the subject of research for over three decades as a platform to protect against or treat a variety of cancers, amyloidosis and infectious diseases. In this review, we discuss mRNA-based approaches for the generation of prophylactic and therapeutic vaccines to HIV. We examine the special immunological hurdles for a vaccine to elicit broadly neutralizing antibodies and effective T cell responses to HIV. Lastly, we outline an mRNA-based HIV vaccination strategy based on the immunobiology of broadly neutralizing antibody development. Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)
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Review
Advancements in mRNA Encoded Antibodies for Passive Immunotherapy
Vaccines 2021, 9(2), 108; https://doi.org/10.3390/vaccines9020108 - 31 Jan 2021
Cited by 12 | Viewed by 2405
Abstract
Monoclonal antibodies are the fastest growing therapeutic class in medicine today. They hold great promise for a myriad of indications, including cancer, allergy, autoimmune and infectious diseases. However, the wide accessibility of these therapeutics is hindered by manufacturing and purification challenges that result [...] Read more.
Monoclonal antibodies are the fastest growing therapeutic class in medicine today. They hold great promise for a myriad of indications, including cancer, allergy, autoimmune and infectious diseases. However, the wide accessibility of these therapeutics is hindered by manufacturing and purification challenges that result in high costs and long lead times. Efforts are being made to find alternative ways to produce and deliver antibodies in more expedient and cost-effective platforms. The field of mRNA has made significant progress in the last ten years and has emerged as a highly attractive means of encoding and producing any protein of interest in vivo. Through the natural role of mRNA as a transient carrier of genetic information for translation into proteins, in vivo expression of mRNA-encoded antibodies offer many advantages over recombinantly produced antibodies. In this review, we examine both preclinical and clinical studies that demonstrate the feasibility of mRNA-encoded antibodies and discuss the remaining challenges ahead. Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)
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Review
An Update on Self-Amplifying mRNA Vaccine Development
Vaccines 2021, 9(2), 97; https://doi.org/10.3390/vaccines9020097 - 28 Jan 2021
Cited by 42 | Viewed by 12897
Abstract
This review will explore the four major pillars required for design and development of an saRNA vaccine: Antigen design, vector design, non-viral delivery systems, and manufacturing (both saRNA and lipid nanoparticles (LNP)). We report on the major innovations, preclinical and clinical data reported [...] Read more.
This review will explore the four major pillars required for design and development of an saRNA vaccine: Antigen design, vector design, non-viral delivery systems, and manufacturing (both saRNA and lipid nanoparticles (LNP)). We report on the major innovations, preclinical and clinical data reported in the last five years and will discuss future prospects. Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)
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Review
Nanomaterial Delivery Systems for mRNA Vaccines
Vaccines 2021, 9(1), 65; https://doi.org/10.3390/vaccines9010065 - 19 Jan 2021
Cited by 136 | Viewed by 24778
Abstract
The recent success of mRNA vaccines in SARS-CoV-2 clinical trials is in part due to the development of lipid nanoparticle delivery systems that not only efficiently express the mRNA-encoded immunogen after intramuscular injection, but also play roles as adjuvants and in vaccine reactogenicity. [...] Read more.
The recent success of mRNA vaccines in SARS-CoV-2 clinical trials is in part due to the development of lipid nanoparticle delivery systems that not only efficiently express the mRNA-encoded immunogen after intramuscular injection, but also play roles as adjuvants and in vaccine reactogenicity. We present an overview of mRNA delivery systems and then focus on the lipid nanoparticles used in the current SARS-CoV-2 vaccine clinical trials. The review concludes with an analysis of the determinants of the performance of lipid nanoparticles in mRNA vaccines. Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)
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Review
Immune Responses Induced by mRNA Vaccination in Mice, Monkeys and Humans
Vaccines 2021, 9(1), 61; https://doi.org/10.3390/vaccines9010061 - 18 Jan 2021
Cited by 47 | Viewed by 7812
Abstract
In this concise review, we summarize the concepts behind mRNA vaccination. We discuss the innate and adaptive immune response generated by mRNA vaccines in different animal models and in humans. We give examples of viral infections where mRNA vaccines have shown to induce [...] Read more.
In this concise review, we summarize the concepts behind mRNA vaccination. We discuss the innate and adaptive immune response generated by mRNA vaccines in different animal models and in humans. We give examples of viral infections where mRNA vaccines have shown to induce potent responses and we discuss in more detail the recent SARS-CoV-2 mRNA vaccine trials in humans. Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)
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Review
Neo-Antigen mRNA Vaccines
Vaccines 2020, 8(4), 776; https://doi.org/10.3390/vaccines8040776 - 18 Dec 2020
Cited by 17 | Viewed by 4451
Abstract
The interest in therapeutic cancer vaccines has caught enormous attention in recent years due to several breakthroughs in cancer research, among which the finding that successful checkpoint blockade treatments reinvigorate neo-antigen-specific T cells and that successful adoptive cell therapies are directed towards neo-antigens. [...] Read more.
The interest in therapeutic cancer vaccines has caught enormous attention in recent years due to several breakthroughs in cancer research, among which the finding that successful checkpoint blockade treatments reinvigorate neo-antigen-specific T cells and that successful adoptive cell therapies are directed towards neo-antigens. Neo-antigens are cancer-specific antigens, which develop from somatic mutations in the cancer cell genome that can be highly immunogenic and are not subjected to central tolerance. As the majority of neo-antigens are unique to each patient’s cancer, a vaccine technology that is flexible and potent is required to develop personalized neo-antigen vaccines. In vitro transcribed mRNA is such a technology platform and has been evaluated for delivery of neo-antigens to professional antigen-presenting cells both ex vivo and in vivo. In addition, strategies that support the activity of T cells in the tumor microenvironment have been developed. These represent a unique opportunity to ensure durable T cell activity upon vaccination. Here, we comprehensively review recent progress in mRNA-based neo-antigen vaccines, summarizing critical milestones that made it possible to bring the promise of therapeutic cancer vaccines within reach. Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)
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Other

Correction
Correction: Kis, Z. et al. Resources, Production Scales and Time Required for Producing RNA Vaccines for the Global Pandemic Demand. Vaccines 2021, 9, 3
Vaccines 2021, 9(3), 205; https://doi.org/10.3390/vaccines9030205 - 01 Mar 2021
Cited by 3 | Viewed by 1217
Abstract
The authors wish to make the following corrections to this paper [...] Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)
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