Nonclinical safety assessment of an mRNA Covid-19 vaccine candidate following repeated administrations and biodistribution.

Messenger RNA (mRNA) vaccines have demonstrated efficacy against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in humans. mRNA technology holds tremendous potential for rapid control and prevention of emergencies due to its flexibility with respect to production, application, and design for an efficacious and safe use in humans. We assessed the toxicity and biodistribution of MRT5500, an mRNA vaccine encoding for the full-length of the SARS-CoV-2 spike protein and delivered by lipid nanoparticles (LNPs) containing a novel ionizable lipid, Lipid-1 in preclinical animal models. In the repeated dose toxicity study, rabbits received three intramuscular (IM) injections of MRT5500 at 3-week interval followed by a 4-week observation period. In an exploratory biodistribution study in mice receiving a single IM injection of an mRNA encoding luciferase encapsulated in an LNP containing Lipid-1, the expression of the luciferase protein was monitored in vivo and ex vivo at several time points. In the regulatory biodistribution study in rabbits receiving a single IM injection of MRT5500, the quantification of the mRNA and the ionizable Lipid-1 were monitored in the same organs and time points as in the exploratory biodistribution study. MRT5500 was safe and well-tolerated with a transient acute phase response/inflammation and an expected vaccine-related immunological response, typical of those observed following a vaccine administration. The biodistribution data demonstrated that the mRNA and Lipid-1 components of the vaccine formulations were mainly detected at the injection site and in the draining lymph nodes. These results support the use of MRT5500 and its deployment into clinical trials.

Seizing opportunities for change at the operational level.

Purpose - This paper presents a method for handling everyday opportunities for improvement, led by floor staff in healthcare institutions. More than 400,000 incidents and accidents were recorded in Quebec healthcare institutions in 2013. The burden of treatment falls on hospital floor staff. The purpose of this paper is to raise the visibility of this problem and support staff better in their efforts to handle opportunities for improvement. Design/methodology/approach - Based on issues identified in the literature, which have been found to exist in various organizations, the method involved reviewing practices in the field, proposing a solution, and testing it to assess its relevance and limitations. The method was tested in partnership with the Centre Hospitalier de l'Université de Montréal, in the internal medicine unit at Hôtel-Dieu campus. The test lasted three months. Indicators from this test have been compared to results in the literature. Findings - The proposed method presents a 68 per cent increase in ideas generated per person and per week compared to the reference study. The mean time for closing actions was about 41 per cent better (lower) than in the reference case. Research limitations/implications - The test lasted 15 weeks; a longer test is needed to collect more data. Practical implications - The first practical implication of this study was the creation of a method allowing employees to seize opportunities for improvement in their daily work. The application of this method revealed: first, the operational nature of the proposal (empowerment of the work team); second, the operationalization of continuous improvement (71 per cent of ideas were finalized while the initiative was monitored); third, the smooth operation of the mechanism for facilitating continuous improvement (organization of weekly meetings and team participation in these meetings in 90 per cent of cases); and fourth, a shared feeling that intra- and inter-team communication had been strengthened. Originality/value - The main value of this paper is that it proposes a simple problem-solving process that gives employees an opportunity to improve their daily work. The originality of this paper resides in comparing results to a standard case and observing an improvement. This paper proposes a new problem-solving structure and tests it scientifically.