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COVID-19疫苗
IMMUNOLOGIC RESEARCH · 2023 ·Vol. 71 ·期 3 ·356-372 · IF 4.4

COVID-19 vaccines adverse events: potential molecular mechanisms

Lamprinou Malamatenia,Sachinidis Athanasios,Stamoula Eleni,Vavilis Theofanis,Papazisis Georgios

COVID-19 is an infectious disease caused by a single-stranded RNA (ssRNA) virus, known as SARS-CoV-2. The disease, since its first outbreak in Wuhan, China, in December 2019, has led to a global pandemic. The pharmaceutical industry has developed several vaccines, of different vector technologies, against the virus. Of note, among these vaccines, seven have been fully approved by WHO. However, despite the benefits of COVID-19 vaccination, some rare adverse effects have been reported and have been associated with the use of the vaccines developed against SARS-CoV-2, especially those based on mRNA and non-replicating viral vector technology. Rare adverse events reported include allergic and anaphylactic reactions, thrombosis and thrombocytopenia, myocarditis, Bell’s palsy, transient myelitis, Guillen-Barre syndrome, recurrences of herpes-zoster, autoimmunity flares, epilepsy, and tachycardia. In this review, we discuss the potential molecular mechanisms leading to these rare adverse events of interest and we also attempt an association with the various vaccine components and platforms. A better understanding of the underlying mechanisms, according to which the vaccines cause side effects, in conjunction with the identification of the vaccine components and/or platforms that are responsible for these reactions, in terms of pharmacovigilance, could probably enable the improvement of future vaccines against COVID-19 and/or even other pathological conditions.

研究领域: 免疫学 · 分子生物学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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Current Drug Safety · 2024 ·Vol. 20 ·期 1 ·33-47 · IF 1.1

A Systematic Review of the COVID Vaccine's Impact on the Nervous System

Viswarupachari Tanguturi Yella,Sumit Pareek,Bhumika Meena,K.S.B.S. Krishna Sasanka,Pugazhenthan Thangaraju,Sree Sudha T Y

Aims & ObjectivesThe objective of this study was to conduct a systematic review of research pertaining to the COVID-19 vaccine and its association with neurological complications.MethodsWe performed a comprehensive search of the literature using Google Scholar, PubMed, and NCBI databases from December 2021 to December 2022. For Google Scholar, PubMed, and NCBI databases we used the following key search terms: “neurological adverse effects”, “COVID-19 vaccination”, “SARS-CoV-2”, CNS complications, and CNS adverse effects. Two reviewer authors individually searched and assessed the titles and abstracts of all articles. The third reviewer resolved the disagreement between them. Data were documented regarding title, study location, type of study, type of COVID-19 vaccine, type of neurological complications/adverse effects, and sample size.ResultsFrom our findings, it is confirmed that these neurological complications like Guillain-Barre syndrome (23.6%), Neuromyelitis Optica spectrum disorder (5.5%), Neuropathy (6.9%), Transverse Myelitis (8.3%) and Acute disseminated Encephalomyelitis (4.1%) are majorly affected in most of the people. The increase in risks associated with SARS-CoV-2 infection far outweighs any previously reported associations with vaccination.ConclusionWe found no safety signal was observed between COVID-19 vaccines and the immune-mediated neurological events. Before assuming a causal relationship, the side effects of the COVID-19 vaccine should first be carefully examined to rule out known associated factors. Symptom onset was within two weeks of vaccination in the majority of cases; as such, this seems to be a high-risk period warranting vigilance.

研究领域: 医学 · 免疫学 · 神经科学
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MOLECULES · 2024 ·Vol. 29 ·期 19 ·4713 · IF 4.2

Effective Synthesis of mRNA during In Vitro Transcription with Fewer Impurities Produced

Wei He,Qi Geng,Guiying Ji,Ji Li,Dan Wang,Yucai He,Qiuheng Jin,Jianren Ye

The remarkable efficacy of COVID-19 vaccines has established mRNA as a highly promising biomedical technology. However, the adequate application of mRNA therapeutics necessitates additional measures to mitigate the inherent immunogenicity, which is predominantly caused by dsRNA. As a byproduct of the in vitro transcription of mRNA, dsRNA was reported to be originated through several distinct mechanisms, including the extension of 3′ loop-back hairpins, the extension of hybridized abortive transcripts, and promoter-independent transcription. The intricate mechanisms involved pose a dilemma as the reduction in dsRNA results in a concomitant decrease in other critical quality attributes of mRNA. Here, we demonstrate that the promoter binding motifs of T7 RNA polymerase directly impact the production of promoter-independent transcription-based dsRNA. Specifically, the G753A mutation significantly reduces the formation of dsRNA byproducts, which can further combine with modified nucleotides to enhance the effectiveness of dsRNA mitigation and with previously reported high-integrity mutation K389A to minimize side effects. Accordingly, the present study reports a cost-effective approach to synthesize high-purity, less immunostimulatory mRNA by using an engineered T7 RNA polymerase mutant.

CAS / MDL: 7786-30-3
研究领域: 分子生物学 · 生物技术 · 药学
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Journal of Materials Chemistry B · 2023 ·Vol. 11 ·期 10 ·2095-2107 · IF 7

A cationic lipid with advanced membrane fusion performance for pDNA and mRNA delivery

Yu Wei,Ting He,Qunjie Bi,Huan Yang,Xueyi Hu,Rongrong Jin,Hong Liang,Yongqun Zhu,Rongsheng Tong,Yu Nie

The success of mRNA vaccines for COVID-19 prevention raised global awareness of the importance of nucleic acid drugs. The approved systems for nucleic acid delivery were mainly formulations of different lipids, yielding lipid nanoparticles (LNPs) with complex internal structures. Due to the multiple components, the relationship between the structure of each component and the overall biological activity of LNPs is hard to study. However, ionizable lipids have been extensively explored. In contrast to former studies on the optimization of hydrophilic parts in single-component self-assemblies, we report in this study on structural alterations of the hydrophobic segment. We synthesize a library of amphiphilic cationic lipids by varying the lengths (C = 8–18), numbers (N = 2, 4), and unsaturation degrees (Ω = 0, 1) of hydrophobic tails. Notably, all self-assemblies with nucleic acid have significant differences in particle size, stability in serum, membrane fusion, and fluidity. Moreover, the novel mRNA/pDNA formulations are characterized by overall low cytotoxicity, efficient compaction, protection, and release of nucleic acids. We find that the length of hydrophobic tails dominates the formation and stability of the assembly. And at a certain length, the unsaturated hydrophobic tails enhance the membrane fusion and fluidity of assemblies and thus significantly affect the transgene expression, followed by the number of hydrophobic tails.

CAS / MDL: 4235-95-4
研究领域: 药学 · 分子生物学 · 纳米技术 · 药物递送系统 · 病毒学
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