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1.
Sci Transl Med ; 15(686): eabn3464, 2023 03 08.
Article in English | MEDLINE | ID: covidwho-2277682

ABSTRACT

As mRNA vaccines have proved to be very successful in battling the coronavirus disease 2019 (COVID-19) pandemic, this new modality has attracted widespread interest for the development of potent vaccines against other infectious diseases and cancer. Cervical cancer caused by persistent human papillomavirus (HPV) infection is a major cause of cancer-related deaths in women, and the development of safe and effective therapeutic strategies is urgently needed. In the present study, we compared the performance of three different mRNA vaccine modalities to target tumors associated with HPV-16 infection in mice. We generated lipid nanoparticle (LNP)-encapsulated self-amplifying mRNA as well as unmodified and nucleoside-modified non-replicating mRNA vaccines encoding a chimeric protein derived from the fusion of the HPV-16 E7 oncoprotein and the herpes simplex virus type 1 glycoprotein D (gDE7). We demonstrated that single low-dose immunizations with any of the three gDE7 mRNA vaccines induced activation of E7-specific CD8+ T cells, generated memory T cell responses capable of preventing tumor relapses, and eradicated subcutaneous tumors at different growth stages. In addition, the gDE7 mRNA-LNP vaccines induced potent tumor protection in two different orthotopic mouse tumor models after administration of a single vaccine dose. Last, comparative studies demonstrated that all three gDE7 mRNA-LNP vaccines proved to be superior to gDE7 DNA and gDE7 recombinant protein vaccines. Collectively, we demonstrated the immunogenicity and therapeutic efficacy of three different mRNA vaccines in extensive comparative experiments. Our data support further evaluation of these mRNA vaccines in clinical trials.


Subject(s)
Cancer Vaccines , Neoplasms , Papillomavirus Infections , Papillomavirus Vaccines , Vaccines, DNA , Animals , Female , Mice , CD8-Positive T-Lymphocytes , Disease Models, Animal , Immunization , Mice, Inbred C57BL , Neoplasms/therapy , Papillomavirus E7 Proteins/genetics , Papillomavirus Infections/complications , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/genetics , Recombinant Proteins , RNA, Messenger/genetics
2.
Thunderbird International Business Review ; 65(1):43709.0, 2023.
Article in English | Scopus | ID: covidwho-2240662

ABSTRACT

The ongoing COVID-19 pandemic has brought terrifying effects for labor markets all around the world. Just as we witness rapid changes in terms of the ways of working (working from home), we are also observing an increase in unemployment. The ways in which major corporations with international operations process their global talent management (GTM) already represents a challenge in relatively stable times and clearly, in a period of such great and sustained turbulence as current experienced, this task becomes still more difficult. Hence, our research aims to study the impact of GTM on the international performance of major companies during the COVID-19 pandemic period. To this end, we surveyed a sample of 59 large companies that act in external markets. Through recourse to multiple linear regressions, we conclude that GTM practices return positive impacts on levels of international performance. Our research returns theoretical implications in terms of the application of integrated GTM models and with the results of significant relevance to corporations operating internationally, and thus enabling them to better understand which strategic human resource management policies will return the best GTM results. © 2022 The Authors. Thunderbird International Business Review published by Wiley Periodicals LLC.

3.
Pediatric Critical Care Medicine Conference: 11th Congress of the World Federation of Pediatric Intensive and Critical Care Societies, WFPICCS ; 23(11 Supplement 1), 2022.
Article in English | EMBASE | ID: covidwho-2190814

ABSTRACT

BACKGROUND AND AIM: Flu is generally benign, although it can sometimes cause serious complications. The goal of the study was to describe the frequency, clinical evolution and complications of influenza in a PICU during five epidemic seasons. METHOD(S): Retrospective observational study of patients with influenza diagnosis admitted to PICU between 2015 and 2022. Demographic variables, morbidity, virus serotype, treatments, mortality and length of the PICU stay, were collected. RESULT(S): Twenty-five patients were admitted into the PICU for influenza, with a median age of 2 (IQR 2 - 6.5) years;52% were male and 40% had associated morbidity. Influenza A accounted for 80%, influenza B 12% and co-infection influenza A+B 8%. Bacterial co-infection was present in 20%, with the most common organisms being streptococcus pneumoniae and streptococcus pyogenes. We observed complications in 80% (sepsis/septic shock, bacterial pneumonia, pleural effusion, myocarditis, supraventricular tachycardia and seizures);64% received antibiotic therapy and 40% Oseltamivir. Non-invasive respiratory support was required in 48%, mechanical ventilation in 28% and inotropicvasopressor drugs in 20%. During the COVID-19 pandemic, there were no admissions for Influenza in the 2020-2021 season, and the first admission occurred in March 2022. Twenty-four months free of influenza were observed. During the study period, median PICU stay was 2 days [IQR 2 - 6.5]. Three children died (12%). CONCLUSION(S): We observed a high rate of complications and mortality, especially during the last SARS-COV-2 prepandemic season, since then we have only had 1 mild case admitted. Preventive measures against SARS-CoV-2 have probably contributed to reducing Influenza transmission.

6.
Thunderbird International Business Review ; : 11, 2022.
Article in English | Web of Science | ID: covidwho-1611358

ABSTRACT

The ongoing COVID-19 pandemic has brought terrifying effects for labor markets all around the world. Just as we witness rapid changes in terms of the ways of working (working from home), we are also observing an increase in unemployment. The ways in which major corporations with international operations process their global talent management (GTM) already represents a challenge in relatively stable times and clearly, in a period of such great and sustained turbulence as current experienced, this task becomes still more difficult. Hence, our research aims to study the impact of GTM on the international performance of major companies during the COVID-19 pandemic period. To this end, we surveyed a sample of 59 large companies that act in external markets. Through recourse to multiple linear regressions, we conclude that GTM practices return positive impacts on levels of international performance. Our research returns theoretical implications in terms of the application of integrated GTM models and with the results of significant relevance to corporations operating internationally, and thus enabling them to better understand which strategic human resource management policies will return the best GTM results.

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