Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
1.
Mol Ther ; 30(5): 1897-1912, 2022 05 04.
Article in English | MEDLINE | ID: covidwho-1586240

ABSTRACT

RNA vaccines have demonstrated efficacy against SARS-CoV-2 in humans, and the technology is being leveraged for rapid emergency response. In this report, we assessed immunogenicity and, for the first time, toxicity, biodistribution, and protective efficacy in preclinical models of a two-dose self-amplifying messenger RNA (SAM) vaccine, encoding a prefusion-stabilized spike antigen of SARS-CoV-2 Wuhan-Hu-1 strain and delivered by lipid nanoparticles (LNPs). In mice, one immunization with the SAM vaccine elicited a robust spike-specific antibody response, which was further boosted by a second immunization, and effectively neutralized the matched SARS-CoV-2 Wuhan strain as well as B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta) variants. High frequencies of spike-specific germinal center B, Th0/Th1 CD4, and CD8 T cell responses were observed in mice. Local tolerance, potential systemic toxicity, and biodistribution of the vaccine were characterized in rats. In hamsters, the vaccine candidate was well-tolerated, markedly reduced viral load in the upper and lower airways, and protected animals against disease in a dose-dependent manner, with no evidence of disease enhancement following SARS-CoV-2 challenge. Therefore, the SARS-CoV-2 SAM (LNP) vaccine candidate has a favorable safety profile, elicits robust protective immune responses against multiple SARS-CoV-2 variants, and has been advanced to phase 1 clinical evaluation (NCT04758962).


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Cricetinae , Humans , Liposomes , Mice , Nanoparticles , RNA, Messenger , Rats , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Tissue Distribution
2.
J Control Release ; 342: 388-399, 2022 02.
Article in English | MEDLINE | ID: covidwho-1562303

ABSTRACT

The efficacy of RNA-based vaccines has been recently demonstrated, leading to the use of mRNA-based COVID-19 vaccines. The application of self-amplifying mRNA within these formulations may offer further enhancement to these vaccines, as self-amplifying mRNA replicons enable longer expression kinetics and more potent immune responses compared to non-amplifying mRNAs. To investigate the impact of administration route on RNA-vaccine potency, we investigated the immunogenicity of a self-amplifying mRNA encoding the rabies virus glycoprotein encapsulated in different nanoparticle platforms (solid lipid nanoparticles (SLNs), polymeric nanoparticles (PNPs) and lipid nanoparticles (LNPs)). These were administered via three different routes: intramuscular, intradermal and intranasal. Our studies in a mouse model show that the immunogenicity of our 4 different saRNA vaccine formulations after intramuscular or intradermal administration was initially comparable; however, ionizable LNPs gave higher long-term IgG responses. The clearance of all 4 of the nanoparticle formulations from the intramuscular or intradermal administration site was similar. In contrast, immune responses generated after intranasal was low and coupled with rapid clearance for the administration site, irrespective of the formulation. These results demonstrate that both the administration route and delivery system format dictate self-amplifying RNA vaccine efficacy.


Subject(s)
COVID-19 , Nanoparticles , Animals , COVID-19 Vaccines , Humans , Liposomes , Mice , RNA, Messenger , SARS-CoV-2 , Vaccine Potency , Vaccines, Synthetic
3.
Journal of Applied Psychology ; 106(9):1283, 2021.
Article in English | ProQuest Central | ID: covidwho-1454725

ABSTRACT

The coronavirus disease-2019 (COVID-19) pandemic has significantly impacted how businesses operate, creating high levels of uncertainty for organizational members. Drawing on social information processing and implicit leadership theories, we developed and tested a model that explains how middle managers' perceptions of CEO narcissism shape their perceived uncertainty in the workplace, particularly when COVID-19 threatens a firm's survival and growth. Managers' sense of uncertainty leads to their engagement in uncertainty-based coping responses, including laissez-faire leadership (i.e., escape coping) and impression management (i.e., control coping). We collected data from 200 middle managers (Study 1;field survey) and 318 working adults (Study 2;online experiment) in North America and the U.K. and found general support for our model. Our research bridges the gap between micro and macro perspectives and provides novel insights into how perceived CEO narcissism can shape managers' behaviors in the context of the COVID-19 pandemic, thereby contributing to the literatures on CEO narcissism, leadership, and crisis management.

4.
J Appl Psychol ; 106(1): 4-14, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1059851

ABSTRACT

During normal and predictable circumstances, employees' occupational calling (i.e., a transcendent passion to use their talent and competencies toward positive societal impact and a sense of meaningfulness derived from working in a chosen occupational domain) is observed to be relatively stable. However, with the onset of the COVID-19 pandemic, circumstances have become anything but normal and predictable, thus putting employees' sense of occupational calling to the test. In this study, we investigate the possibility that occupational calling fluctuates across days during situations of crisis, and we identify antecedents and consequence of such fluctuations. To test our model, we conducted a daily diary study of 66 nurses working in intensive care units over 5 consecutive work days in a specialized Wuhan hospital that only admitted confirmed COVID-19 patients during the peak of the pandemic in China. We found that the daily number of code blue events (i.e., cardiopulmonary resuscitation efforts with the primary goal of patient revival) was positively related to daily occupational calling for nurses. Moreover, individual differences in prosocial motivation predicted the average level and variability of occupational calling over the 5 days, which subsequently related to the nurses' job performance. Our study sheds light on how occupational calling enables people with the needed occupational knowledge and skills to function effectively in crisis situations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
COVID-19/nursing , Critical Care Nursing/methods , Job Satisfaction , Motivation , Nurses/psychology , Work Performance/statistics & numerical data , Adult , COVID-19/psychology , China , Female , Humans , Intensive Care Units , Male , Nurses/statistics & numerical data , Pandemics , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL