Vaccines

Research

Jump to: Review

15 pages, 5690 KiB

Open AccessArticle

mRNA Vaccine for Alzheimer’s Disease: Pilot Study

by Armine Hovakimyan, Garri Chilingaryan, Olga King, Joia Kai Capocchi, Jean Paul Chadarevian, Hayk Davtyan, Roman Kniazev, Michael G. Agadjanyan and Anahit Ghochikyan

Vaccines 2024, 12(6), 659; https://doi.org/10.3390/vaccines12060659 - 14 Jun 2024

Viewed by 3255

Abstract

The escalating global healthcare challenge posed by Alzheimer’s Disease (AD) and compounded by the lack of effective treatments emphasizes the urgent need for innovative approaches to combat this devastating disease. Currently, passive and active immunotherapies remain the most promising strategy for AD. FDA-approved [...] Read more.

The escalating global healthcare challenge posed by Alzheimer’s Disease (AD) and compounded by the lack of effective treatments emphasizes the urgent need for innovative approaches to combat this devastating disease. Currently, passive and active immunotherapies remain the most promising strategy for AD. FDA-approved lecanemab significantly reduces Aβ aggregates from the brains of early AD patients administered biweekly with this humanized monoclonal antibody. Although the clinical benefits noted in these trials have been modest, researchers have emphasized the importance of preventive immunotherapy. Importantly, data from immunotherapy studies have shown that antibody concentrations in the periphery of vaccinated people should be sufficient for targeting Aβ in the CNS. To generate relatively high concentrations of antibodies in vaccinated people at risk of AD, we generated a universal vaccine platform, MultiTEP, and, based on it, developed a DNA vaccine, AV-1959D, targeting pathological Aβ, completed IND enabling studies, and initiated a Phase I clinical trial with early AD volunteers. Our current pilot study combined our advanced MultiTEP technology with a novel mRNA approach to develop an mRNA vaccine encapsulated in lipid-based nanoparticles (LNPs), AV-1959LR. Here, we report our initial findings on the immunogenicity of 1959LR in mice and non-human primates, comparing it with the immunogenicity of its DNA counterpart, AV-1959D. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

► Show Figures

Figure 1

11 pages, 2112 KiB

Open AccessArticle

Evaluation of the Immunological Efficacy of an LNP-mRNA Vaccine Prepared from Varicella Zoster Virus Glycoprotein gE with a Double-Mutated Carboxyl Terminus in Different Untranslated Regions in Mice

by Yunfei Wang, Han Cao, Kangyang Lin, Jingping Hu, Ning Luan and Cunbao Liu

Vaccines 2023, 11(9), 1475; https://doi.org/10.3390/vaccines11091475 - 11 Sep 2023

Cited by 2 | Viewed by 2059

Abstract

Cell-mediated immunity (CMI) plays a key role in the effectiveness of varicella zoster virus (VZV) vaccines, and mRNA vaccines have an innate advantage in inducing CMI. Glycoprotein E (gE) has been used widely as an antigen for VZV vaccines, and carboxyl-terminal mutations of [...] Read more.

Cell-mediated immunity (CMI) plays a key role in the effectiveness of varicella zoster virus (VZV) vaccines, and mRNA vaccines have an innate advantage in inducing CMI. Glycoprotein E (gE) has been used widely as an antigen for VZV vaccines, and carboxyl-terminal mutations of gE are associated with VZV titer and infectivity. In addition, the untranslated regions (UTRs) of mRNA affect the stability and half-life of mRNA in the cell and are crucial for protein expression and antigenic translational efficiency. In this study, three UTRs were designed and connected to the nucleic acid sequence of gE-M, which is double mutated in the extracellular region of gE. Then, mRNA with different nucleic acids was encapsulated in lipid nanoparticles (LNPs), forming three LNP-mRNA VZV vaccines, named gE-M-Z, gE-M-M, and gE-M-P. The immune response elicited by these vaccines in mice was evaluated at intervals of 4 weeks, and the mice were sacrificed 2 weeks after the final immunization. In the results, the gE-M-P group, which retains the nucleic acid sequence of gE-M and is connected to Pfizer/BioNTech’s BNT162b2 UTRs, induced the strongest humoral immune response and CMI. Because CMI is crucial for protection against VZV and for the design of VZV vaccines, this study provides a feasible strategy for improving the effectiveness and economy of future VZV vaccines. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

► Show Figures

Figure 1

16 pages, 17134 KiB

Open AccessArticle

Rapid Identity and Quantity CQA Test for Multivalent mRNA Drug Product Formulations

by Rachel Y. Gao, Christine M. Riley, Evan Toth, Rebecca H. Blair, Megan N. Gerold, Caitlin McCormick, Amber W. Taylor, Tianjing Hu, Kathy L. Rowlen and Erica D. Dawson

Vaccines 2022, 10(10), 1704; https://doi.org/10.3390/vaccines10101704 - 12 Oct 2022

Cited by 3 | Viewed by 3193

Abstract

The COVID-19 pandemic highlighted mRNA as a promising platform for vaccines and therapeutics. Many of the analytical tools used to characterize the critical quality attributes of mRNA are inherently singleplex and are not necessarily optimal from a labor and cost perspective. Here, we [...] Read more.

The COVID-19 pandemic highlighted mRNA as a promising platform for vaccines and therapeutics. Many of the analytical tools used to characterize the critical quality attributes of mRNA are inherently singleplex and are not necessarily optimal from a labor and cost perspective. Here, we demonstrate the feasibility of a multiplexed platform (VaxArray) for efficient identity verification and concentration determination for both monovalent and multivalent mRNA formulations. A model system comprising mRNA constructs for influenza hemagglutinin and neuraminidase was used to characterize the analytical performance metrics for a VaxArray mRNA assay. The assay presented herein had a time to result of less than 2 h, required no PCR-based amplification nor extraction of mRNA from lipid nanoparticles, and exhibited high construct specificity that enabled application to the bivalent mixture. The sensitivity for influenza hemagglutinin and neuraminidase mRNA was sub-µg/mL, which is vaccine-relevant, and the average accuracy (%recovery of a check standard) and precision were 104 ± 2% and 9 ± 2%, respectively. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

► Show Figures

Figure 1

20 pages, 5185 KiB

Open AccessArticle

Impact of DNA Prime/Protein Boost Vaccination against Campylobacter jejuni on Immune Responses and Gut Microbiota in Chickens

by Noémie Gloanec, Daniel Dory, Ségolène Quesne, Véronique Béven, Typhaine Poezevara, Alassane Keita, Marianne Chemaly and Muriel Guyard-Nicodème

Vaccines 2022, 10(6), 981; https://doi.org/10.3390/vaccines10060981 - 20 Jun 2022

Cited by 9 | Viewed by 2554

Abstract

Campylobacteriosis is reported to be the leading zoonosis in Europe, and poultry is the main reservoir of Campylobacter. Despite all the efforts made, there is still no efficient vaccine to fight this bacterium directly in poultry. Recent studies have reported interactions between the [...] Read more.

Campylobacteriosis is reported to be the leading zoonosis in Europe, and poultry is the main reservoir of Campylobacter. Despite all the efforts made, there is still no efficient vaccine to fight this bacterium directly in poultry. Recent studies have reported interactions between the chicken immune system and gut microbiota in response to Campylobacter colonisation. The present study was designed to analyse in more depth the immune responses and caecal microbiota following vaccination with a DNA prime/protein boost flagellin-based vaccine that induces some protection in specific-pathogen-free White Leghorn chickens, as shown previously. These data may help to improve future vaccination protocols against Campylobacter in poultry. Here a vaccinated and a placebo group were challenged by C. jejuni at the age of 19 days. A partial reduction in Campylobacter loads was observed in the vaccinated group. This was accompanied by the production of specific systemic and mucosal antibodies. Transient relatively higher levels of Interleukin-10 and antimicrobial peptide avian β-defensin 10 gene expressions were observed in the vaccinated and placebo groups respectively. The analysis of caecal microbiota revealed the vaccination’s impact on its structure and composition. Specifically, levels of operational taxonomic units classified as Ruminococcaceae and Bacillaceae increased on day 40. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

► Show Figures

Figure 1

Review

Jump to: Research

11 pages, 788 KiB

Open AccessReview

Advances in Nucleic Acid Universal Influenza Vaccines

by Liang Xu, Weigang Ren, Qin Wang and Junwei Li

Vaccines 2024, 12(6), 664; https://doi.org/10.3390/vaccines12060664 - 17 Jun 2024

Cited by 1 | Viewed by 1787

Abstract

Currently, vaccination with influenza vaccines is still an effective strategy to prevent infection by seasonal influenza virus in spite of some drawbacks with them. However, due to the rapid evolution of influenza viruses, including seasonal influenza viruses and emerging zoonotic influenza viruses, there [...] Read more.

Currently, vaccination with influenza vaccines is still an effective strategy to prevent infection by seasonal influenza virus in spite of some drawbacks with them. However, due to the rapid evolution of influenza viruses, including seasonal influenza viruses and emerging zoonotic influenza viruses, there is an urgent need to develop broad-spectrum influenza vaccines to cope with the evolution of influenza viruses. Nucleic acid vaccines might meet the requirements well. Nucleic acid vaccines are classified into DNA vaccines and RNA vaccines. Both types induced potent cellular and humoral immune responses, showing great promise for the development of universal influenza vaccines. In this review, the current status of an influenza universal nucleic acid vaccine was summarized. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

► Show Figures

Figure 1

35 pages, 2243 KiB

Open AccessReview

Precision in Action: The Role of Clustered Regularly Interspaced Short Palindromic Repeats/Cas in Gene Therapies

by Amrutha Banda, Olivia Impomeni, Aparana Singh, Abdul Rasheed Baloch, Wenhui Hu and Dabbu Kumar Jaijyan

Vaccines 2024, 12(6), 636; https://doi.org/10.3390/vaccines12060636 - 7 Jun 2024

Cited by 1 | Viewed by 2538

Abstract

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated enzyme-CAS holds great promise for treating many uncured human diseases and illnesses by precisely correcting harmful point mutations and disrupting disease-causing genes. The recent Food and Drug Association (FDA) approval of the first CRISPR-based gene therapy [...] Read more.

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated enzyme-CAS holds great promise for treating many uncured human diseases and illnesses by precisely correcting harmful point mutations and disrupting disease-causing genes. The recent Food and Drug Association (FDA) approval of the first CRISPR-based gene therapy for sickle cell anemia marks the beginning of a new era in gene editing. However, delivering CRISPR specifically into diseased cells in vivo is a significant challenge and an area of intense research. The identification of new CRISPR/Cas variants, particularly ultra-compact CAS systems with robust gene editing activities, paves the way for the low-capacity delivery vectors to be used in gene therapies. CRISPR/Cas technology has evolved beyond editing DNA to cover a wide spectrum of functionalities, including RNA targeting, disease diagnosis, transcriptional/epigenetic regulation, chromatin imaging, high-throughput screening, and new disease modeling. CRISPR/Cas can be used to engineer B-cells to produce potent antibodies for more effective vaccines and enhance CAR T-cells for the more precise and efficient targeting of tumor cells. However, CRISPR/Cas technology has challenges, including off-target effects, toxicity, immune responses, and inadequate tissue-specific delivery. Overcoming these challenges necessitates the development of a more effective and specific CRISPR/Cas delivery system. This entails strategically utilizing specific gRNAs in conjunction with robust CRISPR/Cas variants to mitigate off-target effects. This review seeks to delve into the intricacies of the CRISPR/Cas mechanism, explore progress in gene therapies, evaluate gene delivery systems, highlight limitations, outline necessary precautions, and scrutinize the ethical considerations associated with its application. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

► Show Figures

Figure 1

23 pages, 1665 KiB

Open AccessReview

Nucleic Acid Vaccines Encoding Proteins and Virus-like Particles for HIV Prevention

by Ferran Tarrés-Freixas, Bonaventura Clotet, Jorge Carrillo and Julià Blanco

Vaccines 2024, 12(3), 298; https://doi.org/10.3390/vaccines12030298 - 12 Mar 2024

Viewed by 2993

Abstract

The development of HIV prophylactic vaccines is facing an impasse, since all phase IIb/III clinical trials were halted in 2023 without demonstrating efficacy. Thus, the field is in need of developing novel immunogens and vaccination strategies that induce broadly neutralising antibodies together with [...] Read more.

The development of HIV prophylactic vaccines is facing an impasse, since all phase IIb/III clinical trials were halted in 2023 without demonstrating efficacy. Thus, the field is in need of developing novel immunogens and vaccination strategies that induce broadly neutralising antibodies together with potent Fc-dependent effector functions, as well as protective cross-reactive CD4⁺ and CD8⁺ T cell responses. Nucleic acid vaccines, particularly mRNA vaccines, have been one of the major groundbreaking advances in the current decade. Nucleic acid vaccines may help recalibrate the HIV vaccine field towards the use of delivery systems that allow the proper expression of immunogens as a sole antigen (i.e., membrane-bound trimeric envelope glycoproteins) or even to be displayed in a multiantigen platform that will be synthesised by the host. In this review, we will summarise how the multiple HIV vaccine strategies pursued in the last 40 years of HIV research have driven current vaccine development, which are the most relevant immunogens identified so far to induce balanced adaptive immune responses, and how they can benefit from the acceptance of nucleic acid vaccines in the market by reducing the limitations of previous delivery systems. The incorporation of nucleic acid vaccines into the current heterogeneous repertoire of vaccine platforms may represent an invaluable opportunity to reignite the fight against HIV. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

► Show Figures

Figure 1

23 pages, 3279 KiB

Open AccessReview

DNA Vaccines: Their Formulations, Engineering and Delivery

by Michael Kozak and Jiafen Hu

Vaccines 2024, 12(1), 71; https://doi.org/10.3390/vaccines12010071 - 11 Jan 2024

Cited by 11 | Viewed by 5343

Abstract

The concept of DNA vaccination was introduced in the early 1990s. Since then, advancements in the augmentation of the immunogenicity of DNA vaccines have brought this technology to the market, especially in veterinary medicine, to prevent many diseases. Along with the successful COVID [...] Read more.

The concept of DNA vaccination was introduced in the early 1990s. Since then, advancements in the augmentation of the immunogenicity of DNA vaccines have brought this technology to the market, especially in veterinary medicine, to prevent many diseases. Along with the successful COVID mRNA vaccines, the first DNA vaccine for human use, the Indian ZyCovD vaccine against SARS-CoV-2, was approved in 2021. In the current review, we first give an overview of the DNA vaccine focusing on the science, including adjuvants and delivery methods. We then cover some of the emerging science in the field of DNA vaccines, notably efforts to optimize delivery systems, better engineer delivery apparatuses, identify optimal delivery sites, personalize cancer immunotherapy through DNA vaccination, enhance adjuvant science through gene adjuvants, enhance off-target and heritable immunity through epigenetic modification, and predict epitopes with bioinformatic approaches. We also discuss the major limitations of DNA vaccines and we aim to address many theoretical concerns. Full article

(This article belongs to the Special Issue Feature Papers of DNA and mRNA Vaccines)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Feature Papers of DNA and mRNA Vaccines

Share This Special Issue

Special Issue Editor

Special Issue Information

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI