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Revolutionizing viral disease vaccination: the promising clinical advancements of non-replicating mRNA vaccines.

ABSTRACT: The mRNA vaccine technology was developed rapidly during the global pandemic of COVID-19. The crucial role of the COVID-19 mRNA vaccine in preventing viral infection also have been beneficial to the exploration and application of other viral mRNA vaccines, especially for non-replication structure mRNA vaccines of viral disease with outstanding research results. Therefore, this review pays attention to the existing mRNA vaccines, which are of great value for candidates for clinical applications in viral diseases. We provide an overview of the optimization of the mRNA vaccine development process as well as the good immune efficacy and safety shown in clinical studies. In addition, we also provide a brief description of the important role of mRNA immunomodulators in the treatment of viral diseases. After that, it will provide a good reference or strategy for research on mRNA vaccines used in clinical medicine with more stable structures, higher translation efficiency, better immune efficacy and safety, shorter production time, and lower production costs than conditional vaccines to be used as preventive or therapeutic strategy for the control of viral diseases in the future.

SUBMITTER: Guo X

PROVIDER: S-EPMC10081822 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Revolutionizing viral disease vaccination: the promising clinical advancements of non-replicating mRNA vaccines.

Guo Xiao X Liu Dongying D Huang Yukai Y Deng Youcai Y Wang Ying Y Mao Jingrui J Zhou Yuancheng Y Xiong Yongai Y Gao Xinghong X

Virology journal 20230407 1

The mRNA vaccine technology was developed rapidly during the global pandemic of COVID-19. The crucial role of the COVID-19 mRNA vaccine in preventing viral infection also have been beneficial to the exploration and application of other viral mRNA vaccines, especially for non-replication structure mRNA vaccines of viral disease with outstanding research results. Therefore, this review pays attention to the existing mRNA vaccines, which are of great value for candidates for clinical applications i ...[more]

PMID: 37029389

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Project description:BackgroundNovel messenger RNA (mRNA)-based vaccines play an important role in current vaccination campaigns against SARS-CoV-2. They are highly efficacious and generally well tolerated. Vaccination in patients with immune-mediated kidney diseases is recommended. A number of cases with de novo or relapsing glomerulonephritis shortly after vaccine application have been reported, some of which presented with gross haematuria.MethodsWe collected 10 cases of macrohaematuria following mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination at our tertiary care institution and referring centres. Additionally, we pooled all 25 published cases from the literature with ours to analyse their clinical characteristics.ResultsMost macrohaematuria episodes (72.2%) began within 2 days after vaccination, the majority after the second dose. In some individuals, repeated episodes occurred after subsequent doses of the same vaccine. A total of 65.7% of patients never had macrohaematuria before. A total of 45.7% were known to suffer from immunoglobulin A nephropathy (IgAN); the rest had no prior renal diagnosis. IgAN was the most frequent new diagnosis, but anti-neutrophil cytoplasmic antibody-associated vasculitis and anti-glomerular basement membrane disease were also identified. Acute kidney injury (AKI) occurred in 28.6% of patients, with an increase in serum creatinine not meeting Kidney Disease: Improving Global Outcomes AKI criteria in 28.6%. Treatment ranged from conservative management, renin-angiotensin-aldosterone system inhibitors, steroids and cyclophosphamide to plasmapheresis. While renal outcomes were mainly favourable in isolated IgAN, they were poor in patients with additional or isolated small vessel vasculitis.ConclusionAwareness of gross haematuria after SARS-CoV-2 vaccination is important. Close follow-up and additional work up, particularly in individuals without known underlying kidney disease or worsening renal function, is essential. For patients with vaccine-associated macrohaematuria, an alternative vaccine class might be considered for subsequent vaccinations.

Project description:BackgroundTrained immunity is the enhanced innate immune response resulting from exposure to pathogens or vaccines against an unrelated pathogen stimulus. Certain vaccines induce a memory like response in monocytes and NK cells, leading to modulation in cytokine production, metabolic changes, and modifications in histone patterns. Here, we hypothesized that vaccination against SARS-CoV-2 could induce the training of monocytes in addition to stimulating the adaptive immune response.MethodsTherefore, we aimed to investigate the immunophenotyping, cytokine and metabolic profile of monocytes from individuals who were completely immunized with two doses of inactivated COVID-19 vaccine or non-replicating viral vector vaccine. Subsequently, we investigated the epigenetic mechanisms underlying monocyte immune training. As a model of inflammatorychallenge, to understand if the monocytes were trained by vaccination and how they were trained, cells were stimulated in vitro with the endotoxin LPS, an unrelated stimulus that would provoke the effects of training.ResultsWhen challenged in vitro, monocytes from vaccinated individuals produced less TNF-α and those who received inactivated vaccine produced less IL-6, whereas vaccination with non-replicating viral vector vaccine induced more IL-10. Inactivated vaccine increased classical monocyte frequency, and both groups showed higher CD163 expression, a hallmark of trained immunity. We observed increased expression of genes involved in glycolysis and reduced IRG1 expression in vaccinated subjects, a gene associated with the tolerance phenotype in monocytes. We observed that both vaccines reduced the chromatin accessibility of genes associated with the inflammatory response, the inactivated COVID-19 vaccine trained monocytes to a regulatory phenotype mediated by histone modifications in the IL6 and IL10 genes, while the non-replicating viral vector COVID-19 vaccine trained monocytes to a regulatory phenotype, mediated by histone modifications in the IL6, IL10, TNF, and CCL2 genes.ConclusionsOur findings support the recognized importance of adopting vaccination against SARS CoV-2, which has been shown to be effective in enhancing the adaptive immune response against the virus and reducing mortality and morbidity rates. Here, we provide evidence that vaccination also modulates the innate immune response by controlling the detrimental inflammatory response to unrelated pathogen stimulation.

Project description:Adenoviral vectors are a safe and potently immunogenic vaccine delivery platform. Non-replicating Ad vectors possess several attributes which make them attractive vaccines for infectious disease, including their capacity for high titer growth, ease of manipulation, safety, and immunogenicity in clinical studies, as well as their compatibility with clinical manufacturing and thermo-stabilization procedures. In general, Ad vectors are immunogenic vaccines, which elicit robust transgene antigen-specific cellular (namely CD8+ T cells) and/or humoral immune responses. A large number of adenoviruses isolated from humans and non-human primates, which have low seroprevalence in humans, have been vectorized and tested as vaccines in animal models and humans. However, a distinct hierarchy of immunological potency has been identified between diverse Ad vectors, which unfortunately limits the potential use of many vectors which have otherwise desirable manufacturing characteristics. The precise mechanistic factors which underlie the profound disparities in immunogenicity are not clearly defined and are the subject of ongoing, detailed investigation. It has been suggested that a combination of factors contribute to the potent immunogenicity of particular Ad vectors, including the magnitude and duration of vaccine antigen expression following immunization. Furthermore, the excessive induction of Type I interferons by some Ad vectors has been suggested to impair transgene expression levels, dampening subsequent immune responses. Therefore, the induction of balanced, but not excessive stimulation of innate signaling is optimal. Entry factor binding or receptor usage of distinct Ad vectors can also affect their in vivo tropism following administration by different routes. The abundance and accessibility of innate immune cells and/or antigen-presenting cells at the site of injection contributes to early innate immune responses to Ad vaccination, affecting the outcome of the adaptive immune response. Although a significant amount of information exists regarding the tropism determinants of the common human adenovirus type-5 vector, very little is known about the receptor usage and tropism of rare species or non-human Ad vectors. Increased understanding of how different facets of the host response to Ad vectors contribute to their immunological potency will be essential for the development of optimized and customized Ad vaccine platforms for specific diseases.

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Revolutionizing viral disease vaccination: the promising clinical advancements of non-replicating mRNA vaccines.

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Revolutionizing viral disease vaccination: the promising clinical advancements of non-replicating mRNA vaccines.

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