mRNA vaccines for infectious diseases: principles, delivery and clinical translation

Lee²,

et al. 2021

Preprint

Background: Dapsone is helpful in the molecular regulation of Nod-like receptor family pyrin domain-containing 3 (NLRP3).Objective: To study the targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by Dapsone should be responsible for its observed preventive treatment effects, functioning as a competitor against Pandemic viral inflammasome.Methods: We compared Hansen's disease (HD) patients with viral respiratory diseases (VRD) after prescribing Dapsone to standard treatment from 2005 to 2020. Results: The 3022 VRD participants who received the dapsone intervention (M = 201, SD = 34) compared to the 3961 VRD participants in the control group (M = 264, SD = 84) demonstrated significantly better peak flow scores, t(28) = -2.7, p = .01. It demonstrated significantly more prevalences of VRD in the DDS unprescribed group. Conclusion: This study is theoretical clinical data to warrant a pilot study with Dapsone for deteriorating leprosy patients at Pandemic.

Section: Discussionmentioning

confidence: 99%

The Viral Respiratory Diseases of Sorok Island at Pandemic

Lee²,

et al. 2021

Preprint

“…The copyright holder for this this version posted December 7, 2021. ; https://doi.org/10.1101/2021.12.04.471206 doi: bioRxiv preprint RNA replication and protein translation without virion assembly in vivo, like RNAbased vaccines in principle 40 . Therefore, we chose EV71-NAEK to validate that its safety and efficacy were comparable with those of currently available vaccines.…”

Section: Discussionmentioning

confidence: 99%

Engineering RNA viruses with unnatural amino acid to evoke adjustable immune response in mice

Zheng

Wang

et al. 2021

Preprint

Ribonucleic acid (RNA) viruses pose heavy burdens on public-health systems. Synthetic biology holds great potential for artificially controlling their replication, a strategy that could be used to attenuate infectious viruses but is still in the exploratory stage. Herein, we used the genetic-code expansion technique to convert Enterovirus 71 (EV71), a model of RNA virus, into a controllable EV71 strain carrying the unnatural amino acid (UAA) Nε-2-azidoethyloxycarbonyl-L-lysine (NAEK), which we termed an EV71-NAEK virus. EV71-NAEK could recapitulate an authentic NAEK time- and dose-dependent infection in vitro and in vivo, which could serve as a novel method to manipulate virulent viruses in conventional laboratories. We further validated the prophylactic effect of EV71-NAEK in two mouse models. In susceptible parent mice, vaccination with EV71-NAEK elicited a strong immune response and potentially protected their neonatal offspring from lethal challenge similar to that of commercial vaccines. Meanwhile, in transgenic mice harboring a PylRS-tRNAPyl CUA pair, substantial elements of genetic-code expansion technology, EV71-NAEK evoked an adjustable neutralizing-antibody response in a strictly external NAEK dose-dependent manner. These findings suggested that EV71-NAEK could be the basis of a feasible immunization program for populations with different levels of immunity. Moreover, we expanded the strategy to generate controllable coxsackieviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for conceptual verification. In combination, these results could underlie a competent strategy for attenuating viruses and priming the immune system via artificial control, which might be a promising direction for the development of amenable vaccine candidates and be broadly applied to other RNA viruses.

“…The ongoing COVID-19 pandemic has led to a paradigm shift in vaccinology, particularly with the use of new vaccine platforms that have not been previously licensed, especially messenger RNA (mRNA) vaccines. By 2019, 15 mRNA vaccine candidates, including three against influenza, were in clinical trials and none in phase III trials [review in (169)]. The COVID-19 pandemic has led to the most rapid vaccine development and approval of the mRNA COVID-19 vaccines to be used in humans.…”

Section: Future Perspectivesmentioning

confidence: 99%

Safety, Immunogenicity, Efficacy and Effectiveness of Inactivated Influenza Vaccines in Healthy Pregnant Women and Children Under 5 Years: An Evidence-Based Clinical Review

2021

Annual influenza vaccination is often recommended for pregnant women and young children to reduce the risk of severe influenza. However, most studies investigating the safety, immunogenicity, and efficacy or effectiveness of influenza vaccines are conducted in healthy adults. In this evidence-based clinical review, we provide an update on the safety profile, immunogenicity, and efficacy/effectiveness of inactivated influenza vaccines (IIVs) in healthy pregnant women and children <5 years old. Six electronic databases were searched until May 27, 2021. We identified 3,731 articles, of which 93 met the eligibility criteria and were included. The IIVs were generally well tolerated in pregnant women and young children, with low frequencies of adverse events following IIV administration; however, continuous vaccine safety monitoring systems are necessary to detect rare adverse events. IIVs generated good antibody responses, and the seroprotection rates after IIVs were moderate to high in pregnant women (range = 65%–96%) and young children (range = 50%–100%), varying between the different influenza types/subtypes and seasons. Studies show vaccine efficacy/effectiveness values of 50%–70% in pregnant women and 20%–90% in young children against lab-confirmed influenza, although the efficacy/effectiveness depended on the study design, host factors, vaccine type, manufacturing practices, and the antigenic match/mismatch between the influenza vaccine strains and the circulating strains. Current evidence suggests that the benefits of IIVs far outweigh the potential risks and that IIVs should be recommended for pregnant women and young children.