Engineering a dual vaccine against COVID-19 and tuberculosis.

The COVID-19 pandemic, caused by SARS-CoV-2 virus, has been one of the top public health threats across the world over the past three years. Mycobacterium bovis BCG is currently the only licensed vaccine for tuberculosis, one of the deadliest infectious diseases in the world, that is caused by Mycobacterium tuberculosis. In the past decades, recombinant M.bovis BCG has been studied as a novel vaccine vector for other infectious diseases in humans besides tuberculosis, such as viral infections. In the current study, we generated a recombinant M. bovis BCG strain AspikeRBD that expresses a fusion protein consisting of M. tb Ag85A protein and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein using synthetic biology technique. Our results show that the recombinant M. bovis BCG strain successfully expressed this fusion protein. Interestingly, the recombinant M. bovis BCG strain AspikeRBD significantly induced SARS-CoV-2 spike-specific T cell activation and IgG production in mice when compared to the parental M.bovis BCG strain, and was more potent than the recombinant M.bovis BCG strain expressing SARS-CoV-2 spike RBD alone. As expected, the recombinant M. bovis BCG strain AspikeRBD activated an increased number of M. tb Ag85A-specific IFNγ-releasing T cells and enhanced IgG production in mice when compared to the parental M.bovis BCG strain or the BCG strain expressing SARS-CoV-2 spike RBD alone. Taken together, our results indicate a potential application of the recombinant M. bovis BCG strain AspikeRBD as a novel dual vaccine against SARS-CoV-2 and M. tb in humans.

Impact of sarcopenia indexes on survival and severe immune acute toxicity in metastatic non-small cell lung cancer patients treated with PD-1 immune checkpoint inhibitors.

BACKGROUND & AIMS: Sarcopenia has long been associated with higher toxicity induced by anti-cancer treatments and shorter survival in patients with solid tumors. The creatinine-to-cystatin ratio (CC ratio, serum creatinine/cystatin C × 100) and the sarcopenia index (SI, serum creatinine × cystatin C (CysC)-based glomerular filtration rate (eGFRCysC)) are have been reported to be correlated with skeletal muscle mass. The aim of this study is to assess primarily whether the CC ratio and the SI could predict mortality in metastatic non-small cell lung cancer (NSCLC) patients treated with PD-1 inhibitors, and secondarily their impact on severe immune-related adverse effects (irAEs). METHODS: From the prospective CERTIM cohort, we analyzed retrospectively stage IV NSCLC patients, who received PD-1 inhibitors between June 2015 and November 2020 in Cochin Hospital (Paris, France). We assessed sarcopenia measuring skeletal muscle area (SMA) by computed tomography and handgrip strength (HGS) by a hand dynamometer. RESULTS: In total, 200 patients were analyzed. The CC ratio and the IS were significantly correlated with SMA and HGS: rCC/SMA = 0.360, rSI/SMA = 0.407, rCC/HGS = 0.331, rSI/HGS = 0.370. In multivariate analysis of overall survival, a lower CC ratio (HR 1.73, P = 0.033) and a lower SI (HR 1.89, P = 0.019) were independent predictors of poor prognosis. In univariate analysis of severe irAEs, CC ratio (OR 1.01, P = 0.628) and SI (OR 0.99, P = 0.595) were not associated with a higher risk of severe irAEs. CONCLUSIONS: In metastatic NSCLC patients treated with PD-1 inhibitors, a lower CC ratio and a lower SI are independent predictors of mortality. However, they are not associated with severe irAEs.

[Goals, motivations, and difficulties of young oncology residents]. / Objectifs, motivations et difficultés des internes en phase socle en oncologie.

INTRODUCTION: The Association for education and research of interns in oncology (AERIO) conducted a national survey of the 2020-year oncology residents promotion in the "phase socle". The objective was to collect and analyze their motivations, as well as the objectives and limitations in the life and career of the residents during this first year of residency. METHODS: A questionnaire included 45 closed questions divided into 6 sections describing: the demographic characteristics of the population, the commitment of the students' and their clinical and academic expectations in the, their training, their life and career objectives, and their commitment in associative life. RESULTS: Seventy-eight of 119 residents participated (66%), of which 68 (87.2%) completed the questionnaire entirely. The population was predominantly women (60%) with a median age of 24 years. The choice between medical or radiation oncology was mostly undefined (87%) and 15% of the residents considered to change their medical specialty. The average hospital work time reported was predominantly between 45 and 65hours per week (83%). Sixty-nine percent were primarily interested in clinical research. One out of two residents (52%) did not have access to their half-day of training per week. DISCUSSION: This national survey made possible to analyze the perception of oncology young residents, as well as their career aspirations and their relationship to research.

[Manual for "Junior Doctors" in medical oncology]. / Guide sur le rôle du « Docteur Junior ¼ en oncologie médicale.

The reform of medical residency introduced in 2017 established the position of Junior Doctor, for its last phase, called the consolidation phase. Its goal is the increasing and supervised autonomy of the resident, in order to better support the transition toward senior practitioner. It appears necessary to define proper guidelines on the status and the specific role of Junior Doctor in medical oncology, in order to help the implementation of the reform of the 3rd cycle. This document is the result of a collaboration between AERIO and CNEC, that respectively represent medical oncology residents and university teachers. It aims to advise and guide local practices, without being compulsory, before the arrival of the first Junior Doctors in November 2021. It explains the Junior Doctors' principal jobs: consultation, multidisciplinary meeting, day clinic, hospitalization, clinical research, quality policy and teaching.