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Bacillus anthracis secretes 2 toxins: lethal toxin (LT) and edema toxin (ET). We investigated their role in the physiopathologic mechanisms of inhalational anthrax by evaluating murine lung dendritic cell (LDC) functions after infection with B. anthracis strains secreting LT, ET, or both or with a nontoxinogenic strain. Three lung cell populations gated on CD11c/CD11b expression were obtained after lung digestion: (1) CD11c(high)/CD11b(low) (alveolar macrophages), (2) CD11c(intermediate (int))/CD11b(int) (LDCs), and (3) CD11c(low)/CD11b(high) (interstitial macrophages or monocytes). After infection with LT-secreting strains, a decrease in costimulatory molecule expression on LDCs was observed. All CD11c(+) cells infected with a nontoxinogenic strain secreted tumor necrosis factor (TNF)- alpha , interleukin (IL)-10, and IL-6. LT-secreting strains inhibited overall cytokine secretion, whereas the ET-secreting strain inhibited only TNF- alpha secretion and increased IL-6 secretion. Similar results were obtained after preincubation with purified toxins. Our results suggest that anthrax toxins secreted during infection impair LDC function and suppress the innate immune response. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Anthrax toxins are critical virulence factors of Bacillus anthracis and Bacillus cereus strains that cause anthrax-like disease, composed of a common binding factor, the protective antigen (PA), and two enzymatic proteins, lethal factor (LF) and edema factor (EF). While PA is required for endocytosis and activity of EF and LF, several studies showed that these enzymatic factors disseminate within the body in the absence of PA after intranasal infection. In an effort to understand the impact of EF in the absence of PA, we used a fluorescent EF chimera to facilitate the study of endocytosis in different cell lines. Unexpectedly, EF was found inside cells in the absence of PA and showed a pole-dependent endocytosis. However, looking at enzymatic activity, PA was still required for EF to induce an increase in intracellular cAMP levels. Interestingly, the sequential delivery of EF and then PA rescued the rise in cAMP levels, indicating that PA and EF may functionally associate during intracellular trafficking, as well as it did at the cell surface. Our data shed new light on EF trafficking and the potential location of PA and EF association for optimal cytosolic delivery.

Background: On May 6, 2022, a powerful outbreak of monkeypox virus (MPXV) had been reported outside of Africa, with many continuing new cases being reported around the world. Analysis of mutations among the 2 different lineages present in the 2021 and 2022 outbreaks revealed the presence of G->A mutations occurring in the 5'GpA context, indicative of APOBEC3 cytidine deaminase activity., Methods: By using a sensitive polymerase chain reaction (differential DNA denaturation PCR) method allowing differential amplification of AT-rich DNA, we analyzed the level of APOBEC3-induced MPXV editing in infected cells and in patients., Results: We demonstrate that G->A hypermutated MPXV genomes can be recovered experimentally from APOBEC3 transfection followed by MPXV infection. Here, among the 7 human APOBEC3 cytidine deaminases (A3A-A3C, A3DE, A3F-A3H), only APOBEC3F was capable of extensively deaminating cytidine residues in MPXV genomes. Hyperedited genomes were also recovered in ∼42% of analyzed patients. Moreover, we demonstrate that substantial repair of these mutations occurs. Upon selection, corrected G->A mutations escaping drift loss contribute to the MPXV evolution observed in the current epidemic., Conclusions: Stochastic or transient overexpression of the APOBEC3F gene exposes the MPXV genome to a broad spectrum of mutations that may be modeling the mutational landscape after multiple cycles of viral replication., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Antibody kinetic curves obtained during a viral infection are often fitted using aggregated patient data, hiding the heterogeneity of individual humoral immune responses. Individual antibody responses can be modeled using the Wood equation and grouped according to their profile. Such modeling takes into account several important kinetic parameters, such as the day when antibody detection becomes positive [daypos], the day of the maximal response [daymax], the maximum antibody level [levelmax], and the day when antibody detection becomes negative [dayneg]. Potential associations between these profiles and studied factors can then be tested., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Inflammatory lesions after Influenza A viruses (IAV) are potential therapeutic target for which better understanding of post-infection immune mechanisms is required. Most studies to evaluate innate immune reactions induced by IAV are based on quantitative/functional methods and anatomical exploration is most often non-existent. We aimed to study pulmonary damage and macrophage recruitment using two-photon excitation microscopy (TPEM) after IAV infection., Methods: We infected C57BL/6 CD11c + YFP mice with A/Puerto Ricco/8/34 H1N1. We performed immune cell analysis, including flow cytometry, cytokine concentration assays, and TPEM observations after staining with anti-F4/80 antibody coupled to BV421. We adapted live lung slice (LLS) method for ex-vivo intravital microscopy to analyze cell motility., Results: TPEM provided complementary data to flow cytometry and cytokine assays by allowing observation of bronchial epithelium lesions and spreading of local infection. Addition of F4/80-BV421 staining allowed us to precisely determine timing of recruitment and pulmonary migration of macrophages. Ex-vivo LLS preserved cellular viability, allowing us to observe acceleration of macrophage motility., Conclusion: After IAV infection, we were able to explore structural consequences and successive waves of innate immune cell recruitment. By combining microscopy, flow cytometry and chemokine measurements, we describe novel and precise scenario of innate immune response against IAV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rivière, Burger, Lefèvre, Garnier, Vigne, Tournier and Billon-Denis.)

Contamination with microorganisms occurs in laboratories but is also of high concern in the context of bioterrorism. Decontamination is a cornerstone that promotes good laboratory practices and occupational health and safety. Among the most resistant structures formed by microorganisms are spores, produced notably by Clostridium and Bacillus species. Here, we compared six products containing four different molecules (hydrogen peroxide, peracetic acid, sodium and calcium hypochlorite) on B. anthracis Sterne spores. We first selected the most efficient product based on its activity against spore suspensions using French and European standards. Four products showed sporicidal activity, of which only two did so in a time frame consistent with good laboratory practices. Then, we tested one of these two products under laboratory conditions on fully virulent B. anthracis spores, during common use and after contamination through a spill of a highly concentrated spore suspension. We, thus, robustly validated a decontaminant based on calcium hypochlorite not only on its ability to kill spores but also on its effectiveness under laboratory conditions. At the end, we were able to assure a complete disinfection in 1 min after spillover and in 2 min for common use., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2023 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Bacillus anthracis is a spore-forming bacterium that produces two major virulence factors, a tripartite toxin with two enzymatic toxic activities and a pseudo-proteic capsule. One of the main described functions of the poly-gamma-d-glutamate capsule is to enable B. anthracis bacilli to escape phagocytosis. Thus, kinetics of expression of the capsule filaments at the surface of the emerging bacillus during germination is an important step for the protection of the nascent bacilli. In this study, through immunofluorescence and electron microscopic approaches, we show the emergence of the capsule through a significant surface of the exosporium in the vast majority of the germinating spores, with co-detection of BclA and capsular material. This suggests that, due to an early capsule expression, the extracellular life of B. anthracis might occur earlier than previously thought, once germination is triggered. This raises the prospect that an anti-capsular vaccine may play a protective role at the initial stage of infection by opsonisation of the nascent encapsulated bacilli before their emergence from the exosporium., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2023 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

The army has always been particularly exposed to the risk of infection, which Alphonse Laveran already analyzed in 1875 in his Traité des maladies et épidémies des armées. Nowadays, the risk of infection is still present, which is why the Armed Forces Health Service (SSA) employs modern research resources in this area structured around the Armed Forces Biomedical Research Institute (IRBA) supported by the Military Training Hospitals (HIA), the Armed Forces Epidemiology and Public Health Center (CESPA), and the Val-de-Grâce School.These resources meet current research needs in infectious and tropical diseases and are preparing to respond to future emergences.Recently, the SSA research has stood out in several epidemics and emergences that have affected the French Armed Forces and the national population., (Copyright © 2023 SFMTSI.)

Introduction: Current approved COVID-19 vaccines, notably mRNA and adenoviral vectored technologies, still fail to fully protect against infection and transmission of various SARS-CoV-2 variants. The mucosal immunity at the upper respiratory tract represents the first line of defense against respiratory viruses such as SARS-CoV-2 and is thus critical to develop vaccine blocking human-to-human transmission., Methods: We measured systemic and mucosal Immunoglobulin A (IgA) response in serum and saliva from 133 healthcare workers from Percy teaching military hospital following a mild infection (SARS-CoV-2 Wuhan strain, n=58) or not infected (n=75), and after SARS-CoV-2 vaccination (Vaxzevria®/Astrazeneca and/or Comirnaty®/Pfizer)., Results: While serum anti-SARS-CoV-2 Spike IgA response lasted up to 16 months post-infection, IgA response in saliva had mostly fallen to baseline level at 6 months post-infection. Vaccination could reactivate the mucosal response generated by prior infection, but failed to induce a significant mucosal IgA response by itself. Early post-COVID-19 serum anti-Spike-NTD IgA titer correlated with seroneutralization titers. Interestingly, its saliva counterpart positively correlated with persistent smell and taste disorders more than one year after mild COVID-19., Discussion: As breakthrough infections have been correlated with IgA levels, other vaccine platforms inducing a better mucosal immunity are needed to control COVID-19 infection in the future. Our results encourage further studies to explore the prognosis potential of anti-Spike-NTD IgA in saliva at predicting persistent smell and taste disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Denis, Garnier, Cheutin, Ferrier, Timera, Jarjaval, Hejl, Billon-Denis, Percy ImmunoCovid group, Ricard, Tournier, Trignol and Mura.)

The human monkeypox disease has mainly been described in Western and Central Africa. Since May 2022, the monkeypox virus has been spreading worldwide in a new epidemiological pattern, where cases result from person-to-person transmission, and develop clinically milder or less typical illness than during previous outbreaks in endemic areas. The newly-emerging monkeypox disease needs to be described over the long term, to improve cases definitions, to implement prompt control measures against epidemics, and to provide supportive care. Hence, we first conducted a review of historical and recent outbreaks to define the full clinical spectrum of the monkeypox disease and its course known so far. Then, we built a self-administrated questionnaire collecting daily symptoms of the monkeypox infection to follow cases and their contacts, even remotely. This tool will assist in the management of cases, the surveillance of contacts, and the conduct of clinical studies., Competing Interests: Declaration of competing interest We declare no competing interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Viruses have been used as tools to prevent viral infections themselves for more than two centuries with impressive success. After the empirical discoveries of the first vaccines, today the development of genetic engineering, molecular virology, reverse genetics, the manipulation of viral genomes, their high-throughput sequencing and their chemical synthesis, the mastery of cell culture and purification methods have greatly benefited the development of viral vaccines. Since smallpox and rabies, the history of vaccinology has followed in the footsteps of the history of virology. New mRNA or viral vector vaccines have emerged in recent years. They were developed and distributed to the population in record time in the face of the Covid pandemic. Viruses in the service of health have a bright future ahead of them, whether to prevent other pandemics, to treat cancer, or to finally control HIV and malaria., (© 2022 médecine/sciences – Inserm.)

The ongoing monkeypox virus (MPXV) outbreak is the largest ever recorded outside of Africa. We isolated and sequenced a virus from the first clinical MPXV case diagnosed in France (May 2022). We report that tecovirimat (ST-246), a US Food and Drug Administration approved drug, is efficacious against this isolate in vitro at nanomolar concentrations, whereas cidofovir is only effective at micromolar concentrations. Our results support the use of tecovirimat in ongoing human clinical trials., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Bacillus anthracis, present as a very durable endospore in soil, causes zoonotic illness which is mainly associated with herbivores and domestic animals. Human cases are scarce and often involve populations close to infected livestock. If anthrax is no longer of public health concern in developed countries, B. anthracis is one of the top-tier biological weapon agents. It is classified by the CDC as a category A agent. Since 1994, emerging strains of Bacillus cereus have been associated with anthrax-like disease in mammals. Some clinical strains of B. cereus harbor anthrax-like plasmid genes (pXO1 and pXO2) associated with non-human primate and human infections, with the same clinical presentation of inhalation anthrax and mortality rates. Although currently restricted to certain limited areas of circulation, the emergence of these new strains of B. cereus extends the list of potential agents possibly usable for bioterrorism or as a biological weapon. It is therefore important to improve our knowledge of the phylogeny within the B. cereus sensu lato group to better understand the origin of these strains. We can then more efficiently monitor the emergence of new strains to better control the risk of infection and limit potentially malicious uses., Competing Interests: The authors declare no conflict of interest.

The French Armed Forces Biomedical Research Institute (IRBA) deeply involved in research on SARS-COV-2, participated in the creation of the Obépine sentinel network in charge of detecting, qualifying and quantifying the virus genome in wastewater in France. During this pandemic, wastewater-based epidemiology has proven to be a first class public health tool for assessing viral dynamics in populations and environment. Obépine has also conducted research demonstrating the low infectivity of faeces and wastewater and allowed for early detection of epidemic waves linked to new variants. The IRBA has adapted this powerful tool to the monitoring of viral infections on board the aircraft carrier Charles-de-Gaulle in order to get an operational system for anticipation after the first local outbreak in 2020. The presence of this surveillance and anticipation tool has allowed a better management of SARS-CoV-2 contingent introductions on board during stopovers or crewmembers entries. The combination of a mandatory vaccination protocol and the surveillance of viral circulation in black waters has made it possible to identify and locate cases, and thus to continue the operational mission in the COVID-19 environment while limiting the spread and preserving the health of the crew. This innovative tool can easily be redirected to the search for any other pathogens in blackwater or even, in the long term, to ensure health surveillance of any military establishment, at sea or on land, in France or on overseas bases., (© 2022 l'Académie nationale de médecine. Published by Elsevier Masson SAS. All rights reserved.)

The recent surge of COVID-19 related to the Omicron variant emergence has thrown a harsh light upon epidemic control in the near future. This should lead the scientific and medical community to question the long-term vaccine strategy for SARS-CoV-2 control. We provide here a critical point of view regarding the virological evolution, epidemiological aspects, and immunological drivers for COVID-19 control, including a vaccination strategy. Overall, we need more innovations in vaccine development to reduce the COVID-19 burden long term. The most adequate answer might be better cooperation between universities, biotech and pharmaceutical companies.

BackgroundSARS-CoV-2 emergence was a threat for armed forces. A COVID-19 outbreak occurred on the French aircraft carrier Charles de Gaulle from mid-March to mid-April 2020.AimTo understand how the virus was introduced, circulated then stopped circulation, risk factors for infection and severity, and effectiveness of preventive measures.MethodsWe considered the entire crew as a cohort and collected personal, clinical, biological, and epidemiological data. We performed viral genome sequencing and searched for SARS-CoV-2 in the environment.ResultsThe attack rate was 65% (1,148/1,767); 1,568 (89%) were included. The male:female ratio was 6.9, and median age was 29 years (IQR: 24-36). We examined four clinical profiles: asymptomatic (13.0%), non-specific symptomatic (8.1%), specific symptomatic (76.3%), and severe (i.e. requiring oxygen therapy, 2.6%). Active smoking was not associated with severe COVID-19; age and obesity were risk factors. The instantaneous reproduction rate (R t ) and viral sequencing suggested several introductions of the virus with 4 of 5 introduced strains from within France, with an acceleration of R t when lifting preventive measures. Physical distancing prevented infection (adjusted OR: 0.55; 95% CI: 0.40-0.76). Transmission may have stopped when the proportion of infected personnel was large enough to prevent circulation (65%; 95% CI: 62-68).ConclusionNon-specific clinical pictures of COVID-19 delayed detection of the outbreak. The lack of an isolation ward made it difficult to manage transmission; the outbreak spread until a protective threshold was reached. Physical distancing was effective when applied. Early surveillance with adapted prevention measures should prevent such an outbreak.

The development of new vaccines has traditionally been a long-term job, although recent experience with the emergence of Covid-19 has caused development and production delays to skyrocket. The fact remains that the development of vaccines in the preclinical phases and in phases 1 and 2 of clinical development is based on the study of the specific immune response of the adaptive immune system., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Anthrax is an acute disease caused by the bacterium Bacillus anthracis , and is a potential biowarfare/bioterrorist agent. Its pulmonary form, caused by inhalation of the spores, is highly lethal and is mainly related to injury caused by the toxins secretion. Antibodies neutralizing the toxins of B. anthracis are regarded as promising therapeutic drugs, and two are already approved by the Federal Drug Administration. We developed a recombinant human-like humanized antibody, 35PA83 6.20, that binds the protective antigen and that neutralized anthrax toxins in-vivo in White New Zealand rabbits infected with the lethal 9602 strain by intranasal route. Considering these promising results, the preclinical and clinical phase one development was funded and a program was started. Unfortunately, after 5 years, the preclinical development was cancelled due to industrial and scientific issues. This shutdown underlined the difficulty particularly, but not only, for an academic laboratory to proceed to clinical development, despite the drug candidate being promising. Here, we review our strategy and some preliminary results, and we discuss the issues that led to the no-go decision of the pre-clinical development of 35PA83 6.20 mAb. Our review provides general information to the laboratories planning a (pre-)clinical development.

Several COVID-19 vaccines have now been deployed to tackle the SARS-CoV-2 pandemic, most of them based on messenger RNA or adenovirus vectors.The duration of protection afforded by these vaccines is unknown, as well as their capacity to protect from emerging new variants. To provide sufficient coverage for the world population, additional strategies need to be tested. The live pediatric measles vaccine (MV) is an attractive approach, given its extensive safety and efficacy history, along with its established large-scale manufacturing capacity. We develop an MV-based SARS-CoV-2 vaccine expressing the prefusion-stabilized, membrane-anchored full-length S antigen, which proves to be efficient at eliciting strong Th1-dominant T-cell responses and high neutralizing antibody titers. In both mouse and golden Syrian hamster models, these responses protect the animals from intranasal infectious challenge. Additionally, the elicited antibodies efficiently neutralize in vitro the three currently circulating variants of SARS-CoV-2., (© 2021. The Author(s).)

Objective: A better understanding of the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is critical to predict its dynamics within the general population and its impact on the vaccination strategy. This study assessed the persistence of neutralizing antibody (Nab) activity and SARS-CoV-2 serology in serum samples of mild and asymptomatic patients 9 months post symptom onset (PSO) in a primary care context among immunocompetent adults., Methods: A longitudinal cohort of crew members (CMs) exposed to coronavirus disease 2019 (COVID-19) during an outbreak of SARS-CoV-2 on the French aircraft carrier 'Charles de Gaulle' in April 2020 was created. CMs infected with COVID-19 and with positive serology at the end of quarantine were tested 9 months PSO. Samples were collected 18 and 280 days PSO. For each patient, both serology and serum viral neutralizing activity were performed., Results: In total, 86 CMs were analysed. Samples were collected 18 and 280 days PSO. The seroconversion rates were 100% and 93% (82/86) at 18 and 280 days PSO, respectively, and 72.7% of patients exhibited persistent Nab activity at 9 months, regardless of disease severity., Conclusion: Nab activity persists for up to 9 months following asymptomatic/mild COVID-19 among young adults, regardless of serological results., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Vaccination plays a key role in the prevention of the infectious diseases, which the armed forces are exposed to during overseas deployments. Historically, the French military health service have always contributed greatly to progress in vaccination. The military immunization schedule has often been used as a model for the national schedule. It is a powerful tool, which is constantly evolving to take into account the risks of infection inherent in deployment and to include new scientific data, while still remaining aware of the limitations of vaccination from an individual and collective standpoint. In the current context of increasingly fast emergence or re-emergence of pathogens with a high epidemic potential, developing preventive medical measures is more necessary than ever before, and the French military health service is actively participating., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: We report here the case of two coworkers infected by the same SARS-CoV-2 strain, presenting two different immunological outcomes., Case: One patient presented a strong IgG anti-receptor-binding domain immune response correlated with a low and rapidly decreasing titer of neutralizing antibodies. The other patient had a similar strong IgG anti-receptor-binding domain immune response but high neutralizing antibody titers., Discussion and Conclusion: Thus, host individual factors may be the main drivers of the immune response varying with age and clinical severity., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

The eradication of infectious diseases has been achieved only once in history, in 1980, with smallpox. Since 1988, significant effort has been made to eliminate poliomyelitis viruses, but eradication is still just out of reach. As the goal of viral disease eradication approaches, the ability to recreate historically eradicated viruses using synthetic biology has the potential to jeopardize the long-term sustainability of eradication. However, the emergence of the severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 pandemic has highlighted our ability to swiftly and resolutely respond to a potential outbreak. This virus has been synthetized faster than any other in the past and is resulting in vaccines before most attenuated candidates reach clinical trials. Here, synthetic biology has the opportunity to demonstrate its truest potential to the public and solidify a footing in the world of vaccines.

Ricin, a highly toxic protein from Ricinus communis , is considered a potential biowarfare agent. Despite the many data available, no specific treatment has yet been approved. Due to their ability to provide immediate protection, antibodies (Abs) are an approach of choice. However, their high specificity might compromise their capacity to protect against the different ricin isoforms (D and E) found in the different cultivars. In previous work, we have shown the neutralizing potential of different Abs (43RCA-G1 (anti ricin A-chain) and RB34 and RB37 (anti ricin B-chain)) against ricin D. In this study, we evaluated their protective capacity against both ricin isoforms. We show that: (i) RB34 and RB37 recognize exclusively ricin D, whereas 43RCA-G1 recognizes both isoforms, (ii) their neutralizing capacity in vitro varies depending on the cultivar, and (iii) there is a synergistic effect when combining RB34 and 43RCA-G1. This effect is also demonstrated in vivo in a mouse model of intranasal intoxication with ricin D/E (1:1), where approximately 60% and 40% of mice treated 0 and 6 h after intoxication, respectively, are protected. Our results highlight the importance of evaluating the effectiveness of the Abs against different ricin isoforms to identify the treatment with the broadest spectrum neutralizing effect.

Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest.

Coronavirus disease (COVID)-19 is an emerging pandemic infection whose significant ability to spread in a naïve population is well established. The first response of states to the COVID-19 outbreak was to impose lock-down and social barrier measures, such as wearing a surgical mask or social distancing. One of the consequences of this pandemic in terms of public health was the suspension or slowdown of infant vaccination campaigns, in almost all countries. The indirect effects of COVID-19 may therefore weigh on mortality from measles and polio in developing countries. In this pandemic chaos, the only hope lies in the rapid development of an effective vaccine against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). However, acceptance of this vaccine has not yet been won, as beyond the many unknowns that will inevitably weigh around such rapid development, skepticism among vaccine hesitants is growing., (© 2020 médecine/sciences – Inserm.)

SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2, which emerged in China at the end of 2019, is responsible for a global health crisis resulting in the confinement of more than 3 billion people worldwide and the sharp decline of the world economy. In this context, a race against the clock is launched in order to develop a treatment to stop the pandemic as soon as possible. A study published in Nature by the Volker Thiel team reports the development of reverse genetics for SARS-CoV-2 allowing them to recreate the virus in just a few weeks. The perspectives of this work are very interesting since it will allow the genetic manipulation of the virus and thus the development of precious tools which will be useful to fight the infection. Even though this approach represents a technological leap that will improve our knowledge of the virus, it also carries the germ of possible misuse and the creation of the virus for malicious purposes. The advantages and disadvantages of recreating SARS-CoV-2 in this pandemic period are discussed in this mini-synthesis., (© 2020 médecine/sciences – Inserm.)

Anthrax toxins are produced by Bacillus anthracis throughout infection and shape the physiopathogenesis of the disease. They are produced in low quantities but are highly efficient. They have thus been long ignored, but recent biochemical methods have improved our knowledge in animal models. This article reviews the various methods that have been used and how they could be applied to clinical diagnosis.

Background: Lethal and edema toxins are critical virulence factors of Bacillus anthracis. Few data are available on their presence in the early stage of intranasal infection., Methods: To investigate the diffusion of edema factor (EF) and lethal factor (LF), we use sensitive quantitative methods to measure their enzymatic activities in mice intranasally challenged with a wild-type B anthracis strain or with an isogenic mutant deficient for the protective antigen., Results: One hour after mouse challenge, although only 7% of mice presented bacteremia, LF and EF were detected in the blood of 100% and 42% of mice, respectively. Protective antigen facilitated the diffusion of LF and EF into the blood compartment. Toxins played a significant role in the systemic dissemination of B anthracis in the blood, spleen, and liver. A mouse model of intoxination further confirmed that LT and ET could diffuse rapidly in the circulation, independently of bacteria., Conclusions: In this inhalational model, toxins have disseminated rapidly in the blood, playing a significant and novel role in the early systemic diffusion of bacteria, demonstrating that they may represent a very early target for the diagnosis and the treatment of anthrax., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Inhalational anthrax caused by Bacillus anthracis , a spore-forming Gram-positive bacterium, is a highly lethal infection. Antibodies targeting the protective antigen (PA) binding component of the toxins have recently been authorized as an adjunct to antibiotics, although no conclusive evidence demonstrates that anthrax antitoxin therapy has any significant benefit. We discuss here the rational basis of anti-PA development regarding the pathogenesis of the disease. We argue that inductive reasoning may induce therapeutic bias. We identified anthrax animal model analysis as another bias. Further studies are needed to assess the benefit of anti-PA antibodies in the treatment of inhalational anthrax, while a clearer consensus should be established around what evidence should be proven in an anthrax model., (Copyright © 2019 Tournier et al.)

The eradication of infectious diseases is one of the oldest dreams of mankind. It has been materialized only once in History with smallpox in 1980. Considerable efforts are being developed against poliomyelitis viruses since 1988, but the ultimate goal of eradication is not yet achieved. Paradoxically, while the objective of having eradicated these two viral diseases is approaching, synthetic biology multiplies the prowesses of virus "neosynthesis", imperiling at least virtually the durability of these advances. This article emphasizes the potential of a new biology on one side, and the difficult reality of the fight against infections on the other., (© 2019 médecine/sciences – Inserm.)

Measles virus has been successfully attenuated on chicken embryo cells to obtain a highly efficient and safe live attenuated vaccine, administered thus far to billions of children. Measles virus attenuation has long been described to involve a modification of cellular tropism with the use of human CD46 ubiquitous receptor. Nevertheless, the use of this receptor in vivo is not obvious. In this study we use four different mouse models to decipher the respective part of hCD46 receptor and type-I interferon response in measles host restriction. We observed that only type-I interferon restricts viral replication of attenuated MV Schwarz strain in mice, independently of the presence of hCD46 receptor. By comparing measles virus immunogenicity in the different models, we confirmed that there was no impact on the absence of this receptor on the immune response. Therefore, we propose to simplify the mouse model., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Exogenous activation of invariant NKT (iNKT) cells by the superagonist α-galactosylceramide (α-GalCer) can protect against cancer, autoimmune diseases, and infections. In the current study, we investigated the effect of α-GalCer against Bacillus anthracis infection, the agent of anthrax. Using an experimental model of s.c. B. anthracis infection (an encapsulated nontoxigenic strain), we show that concomitant administration of α-GalCer delayed B. anthracis systemic dissemination and prolonged mouse survival. Depletion of subcapsular sinus CD169-positive macrophages by clodronate-containing liposome was associated with a lack of iNKT cell activation in the draining lymph nodes (dLNs) and prevented the protective effect of α-GalCer on bacterial dissemination out of the dLNs. Production of IFN-γ triggered chemokine (C-C motif) ligand 3 synthesis and recruitment of neutrophils in the dLNs, leading to the restraint of B. anthracis dissemination. Our data highlight a novel immunological pathway leading to the control of B. anthracis infection, a finding that might lead to improved therapeutics based on iNKT cells., (Copyright © 2016 by The American Association of Immunologists, Inc.)

In vivo microscopy has recently become a gold standard in lung immunology studies involving small animals, largely benefiting from the democratization of multiphoton microscopy allowing for deep tissue imaging. This technology represents currently our only way of exploring the lungs and inferring what happens in human respiratory medicine. The interest of lung in vivo microscopy essentially relies upon its relevance as a study model, fulfilling physiological requirements in comparison with in vitro and ex vivo experiments. However, strategies developed in order to overcome movements of the thorax caused by breathing and heartbeats remain the chief drawback of the technique and a major source of invasiveness. In this context, minimizing invasiveness is an unavoidable prerequisite for any improvement of lung in vivo microscopy. This review puts into perspective the main techniques enabling lung in vivo microscopy, providing pros and cons regarding invasiveness., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The lung is the terminal target of Bacillus anthracis before death, whatever the route of infection (cutaneous, inhalational, or digestive). During a cutaneous infection in absence of toxins, we observed encapsulated bacteria colonizing the alveolar capillary network, bacteria and hemorrhages in alveolar and bronchiolar spaces, and hypoxic foci in the lung (endothelial cells) and brain (neurons and neuropil). Circulating encapsulated bacteria were as chains of approximately 13 µm in length. Bacteria of such size were immediately trapped within the lung capillary network, but bacteria of shorter length were not. Controlling lung-targeted pathology would be beneficial for anthrax treatment., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)