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L’objectif d’un « au-delà du PIB » mobilise aujourd’hui de nombreux acteurs. Si les réflexions pionnières se sont d’abord cantonnées aux milieux écologistes, à la société civile organisée et aux politiques locales, elles ont récemment intégré les sphères institutionnelles nationales et internationales. Mais de quoi l’intérêt des acteurs institutionnels pour cette question est-il le signe ? Un « au-delà du PIB » serait-il un objectif rhétorique par défaut, en l'absence de stratégie crédible de sortie de crise, ou le signe d’un véritable changement paradigmatique ? L’article entend élucider ces questions par l’analyse des discours d’acteurs institutionnels sur un « au-delà du PIB ». Les débats institutionnels, bien qu’intégrant de nouveaux enjeux comme la soutenabilité et le bien-être, restent dominés par des intérêts et contraintes de court terme, dont la croissance du PIB demeure un élément central. Derrière l’illusion démocratique, les ambiguïtés conceptuelles liées à un « au-delà du PIB » tendent à asseoir un rapport de force existant.

Purpose of Review: Tuberculosis (TB) remains a global public health emergency and caused 1.6 million deaths in 2021. The aim of this review is to provide recent updates on advances in TB vaccine development for prevention and adjunct therapy., Recent Findings: Targets use indications guiding late stage TB vaccine development have been established, namely: (i) Prevention of disease (PoD), (ii) Prevention of recurrent disease (PoR), (iii) Prevention of established infection in previously uninfected patients (PoI), and (iv) Adjunctive immunotherapy. Novel approaches include vaccines designed to induce immune responses beyond established CD4+, Th1-biased T cell immunity, novel animal models for use in challenge/protection studies, and controlled human infection models to generate vaccine efficacy data., Summary: Recent efforts at developing effective TB vaccines for prevention and adjunct treatment utilising new targets and technologies have yielded 16 candidate vaccines demonstrating proof of concept for inducing potentially protective immune responses to TB which is currently under evaluation in different stages of clinical trials., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Like many scientists, ecologists depend heavily on continuous uninterrupted data in order to understand better the object of their study. Although this might be straightforward to achieve under controlled laboratory conditions, the situation is easily complicated under field conditions where sensors and data transmission are affected by harsh weather, living organisms, changes in atmospheric conditions etc. This often results in parts of the data being corrupted or missing altogether. We propose the use of the most recent machine-learning techniques to reverse such data losses in multi-channel time series. In particular, we focus on tree stem growth data obtained from the TreeNet project, which monitors the changes in stem radius and environmental conditions of a few hundred trees across Switzerland. In the first part of the study, we test the performance of five architectures based on encoders and recurrent and convolutional neural networks, and we show that a deep neural network combining long short-term memory with one-dimensional convolutional layers performs the best. In the second part, we adopt this model to reconstruct the original TreeNet dataset, which we then use in a separate classification problem to show the effect of the proposed gap-filling procedure.

Background: A vaccine (HB-101) consisting of 2 nonreplicating lymphocytic choriomeningitis virus (LCMV) vectors expressing the human cytomegalovirus antigens glycoprotein B (gB) and the 65-kD phosphoprotein (pp65), respectively, is in development to prevent cytomegalovirus infection., Methods: HB-101 was tested in cytomegalovirus-naive, healthy adults in a randomized, double-blind, placebo-controlled, dose-escalation Phase I trial. Fifty-four subjects received low, medium, or high dose of HB-101 or placebo by intramuscular administration at Month 0, 1, and 3. Safety and immunogenicity were the respective primary and secondary endpoints. Subjects were followed for 12 months after the initial immunization., Results: Vaccination was associated with transient mild to moderate adverse events. HB-101 administration induced dose-dependent gB- and pp65-specific cellular responses, dominated by pp65-specific CD8 T cells, a high fraction of which were polyfunctional. Two administrations were sufficient to elicit dose-dependent gB-binding and cytomegalovirus-neutralizing antibodies (Abs). Cytomegalovirus-specific immune responses were boosted after each administration. Only 1 of 42 vaccine recipients mounted a transient LCMV vector-neutralizing Ab response., Conclusions: HB-101 was well tolerated and induced cytomegalovirus-specific polyfunctional CD8 T-cell and neutralizing Ab responses in the majority of subjects. Lack of vector-neutralizing Ab responses should facilitate booster vaccinations. These results justify further clinical evaluation of this vaccine candidate., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Two proof of concept clinical trials with TB vaccines demonstrate that new approaches can prevent sustained TB infection in adolescents (BCG revaccination) and TB disease in adults (M72/ASO1 E ) (Nemes et al., 2018; Tait et al., 2019) [1,2]. Both approaches are in late stage development and provide motivation and rationale to invest into a global TB vaccine pipeline. This pipeline needs to be diverse to address TB-specific challenges including variation in target populations, uncertainties in animal model predictivity and lack of immune correlates of protection. It requires that individual vaccine candidates must be advanced rationally and that the global pipeline must be managed in the most nimble and resource-efficient way, especially in the current constrained funding environment. The TB Vaccine Development Pathway is a webtool which has been developed as an offer to the field to provide a source of information and guidance covering vaccine development from discovery to implementation. It is underpinned by generic and TB vaccine-specific guidelines, regulatory frameworks and best practice, and was compiled by a multi-disciplinary team of scientific and technical experts with the input of the TB vaccine community. The Pathway is a unique tool to guide and accelerate the development of TB vaccine candidates and may be useful for other vaccine development fields., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Treating tuberculosis (TB) requires a multidrug course of treatment lasting 6 months, or longer for drug-resistant TB, which is difficult to complete and often not well tolerated. Treatment failure and recurrence after end-of-treatment can have devastating consequences, including progressive debilitation, death, the transmission of Mycobacterium tuberculosis - the infectious agent responsible for causing TB - to others, and may be associated with the development of drug-resistant TB. The burden on health systems is important, with severe economic consequences. Vaccines have the potential to serve as immunotherapeutic adjuncts to antibiotic treatment regimens for TB. A therapeutic vaccine for TB patients, administered towards completion of a prescribed course of drug therapy or at certain time(s) during treatment, could improve outcomes through immune-mediated control and even clearance of bacteria, potentially prevent re-infection, and provide an opportunity to shorten and simplify drug treatment regimens. The preferred product characteristics (PPC) for therapeutic TB vaccines described in this document are intended to provide guidance to scientists, funding agencies, public and private sector organizations developing such vaccine candidates. This document presents potential clinical end-points for evidence generation and discusses key considerations about potential clinical development strategies., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Dengue is a public health problem in the tropics and subtropics. There are several vaccine candidates in clinical development. However, there may be gaps in the new vaccine introduction after vaccine licensure before it becomes available in developing countries. In anticipation of the first dengue vaccine candidate to be licensed, Dengue Vaccine Initiative (DVI) and, its predecessor, Pediatric Dengue Vaccine Initiative (PDVI) have been working on points for consideration to accelerate evidence-based dengue vaccine introduction, once a vaccine becomes available. In this paper, we review the history of PDVI and its successor, the DVI, and elaborate on the points of consideration for dengue vaccine introduction.

Unlabelled: Rotavirus gastroenteritis is one of the leading causes of diarrhea in Indian children less than 2 years of age. The 116E rotavirus strain was developed as part of the Indo-US Vaccine Action Program and has undergone efficacy trials. This paper reports the efficacy and additional safety data in children up to 2 years of age. In a double-blind placebo controlled multicenter trial, 6799 infants aged 6-7 weeks were randomized to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. The primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. We randomly assigned 4532 and 2267 subjects to receive vaccine and placebo, respectively, with over 96% subjects receiving all three doses of the vaccine or placebo. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. The overall incidence of severe RVGE per 100 person years was 1.3 in the vaccine group and 2.9 in the placebo recipients. Vaccine efficacy against severe rotavirus gastroenteritis in children up to 2 years of age was 55.1% (95% CI 39.9 to 66.4; p<0.0001); vaccine efficacy in the second year of life of 48.9% (95% CI 17.4 to 68.4; p=0.0056) was only marginally less than in the first year of life [56.3% (95% CI 36.7 to 69.9; p<0.0001)]. The number of infants needed to be immunized to prevent one episode of severe RVGE in the first 2 years of life was 40 (95% CI 28.0 to 63.0) and for RVGE of any severity, it was 21 (95% CI 16.0 to 32.0). Serious adverse events were observed at the same rates in the two groups. None of the eight intussusception events occurred within 30 days of a vaccine dose and all were reported only after the third dose. The sustained efficacy of the 116E in the second year of life is reassuring., Clinical Trial Registry: The trial is registered with Clinical Trial Registry-India (# CTRI/2010/091/000102) and Clinicaltrials.gov (# NCT01305109)., (Copyright © 2014. Published by Elsevier Ltd.)

Background: Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India., Methods: We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109)., Findings: 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; p<0·0001) in the first year of life. The number of infants needed to be immunised to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5 in the vaccine group and 3·2 in the placebo group, with an incidence rate ratio of 0·46 (95% CI 0·33-0·65). Prevalence of immediate, solicited, and serious adverse events was similar in both groups. One case of urticaria in the vaccine group and one each of acute gastroenteritis and suspected sepsis in the placebo group were regarded as related to the study product. We recorded six cases of intussusception in the vaccine group and two in the placebo group, all of which happened after the third dose. 25 (<1%) infants in the vaccine group and 17 (<1%) in the placebo group died; no death was regarded as related to the study product., Interpretation: Monovalent human-bovine (116E) rotavirus vaccine is effective and well tolerated in Indian infants., Funding: Department of Biotechnology and the Biotechnology Industry Research Assistance Council, Government of India; Bill & Melinda Gates Foundation to PATH, USA; Research Council of Norway; UK Department for International Development; National Institutes of Health, Bethesda, USA; and Bharat Biotech International, Hyderabad, India., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

3 beta-hydroxysteroid dehydrogenase deficiency is a disorder of steroid biosynthesis resulting in decreased production of all 3 groups of adrenal steroids. The symptomatology includes congenital adrenal hyperplasia disorders and ambiguous genitalia in 46, XY males. 3beta-HSD deficiency is a rare autosomal recessive genetic disorder. Much heterogeneity exists in the clinical presentation of this disorder.

Several formulations of a recombinant chimeric respiratory syncytial virus (RSV) vaccine consisting of the extramembrane domains of the F and G glycoproteins (FG) were tested in cotton rats to evaluate efficacy and safety. The FG vaccine was highly immunogenic, providing nearly complete resistance to pulmonary infection at doses as low as 25 ng in spite of inducing relatively low levels of serum neutralizing antibody at low vaccine doses. Upon RSV challenge animals primed with FG vaccine showed quite mild alveolitis and interstitial pneumonitis, which were eliminated by the addition of monophosphoryl lipid A to the formulation.

The case of a 7 year-old who presented with lymphangitic carcinomatosis revealed by lung biopsy and secondary to renal adenocarcinoma is described. This biopsy was performed because of radiologic and clinical signs associating bilateral interstitial infiltrates, mediastinal adenopathy and gradually increasing respiratory distress. Despite treatment, the child died two weeks later.