Splenic lymphocytes derived from DENV-4-DNAv inoculated group demonstrated high proliferative response to inactivated dengue virus. Fig. 4 shows the results obtained in the confirmatory experiment. T cell proliferation in the DENV-4-DNAv group was approximately 20%, similar to that observed in DENV-4 immunized group, suggesting that our vaccine induced a good cellular immune stimulation. In addition, proliferation responses of DENV-4-DNAv group were higher than that observed in the negative control. The results in Fig. 4 are representative of four animals

per group, but in both experiments all mouse-inoculated groups responded in a similar fashion. DENV-4-DNAv vaccine candidate was evaluated for their ability to induce protective immunity against lethal challenge with DENV-4. Groups of 10 three-week-old BALB/c mice were immunized with recombinant plasmid, positive and negative control Dolutegravir clinical trial mice were immunized with

DENV-4 (1 × 105 PFU) and with 100 μg of pCI, respectively. As shown in Fig. 5, immunization with DENV-4-DNAv induced significant protection against DENV-4 challenge, comparable to that observed in DENV-4 inoculated mice, where 80% of the challenged mice survived. However, only 20% survival was observed after immunization with pCI and no survival was obtained with PBS immunization. The protection levels of the immunized S3I-201 in vitro group was statistical significant (p = 0.01), when this group was compared with pCI immunized animals (Mantel-Cox statistical analysis). Dengue is responsible for the highest mortality and morbidity rates than any other disease caused by an arbovirus in humans [22]. Annually, more than 100 million cases of dengue fever and about 500,000 cases of DHF occur, and since there is no treatment for these diseases, immunization may provide the most realistic approach for controlling dengue infections [1] and [2]. The

efforts the for the development of vaccines against to dengue began more than 50 years ago, when serious cases of the disease were recognized, and since the 1970s the World Health Organization has sponsored several studies to obtain these vaccines [23] and [24]. A recombinant DNA vaccine is a new approach consisting of a plasmid backbone and the gene encoding the antigen of interest, and it is considered efficient due to the fact that it elicits both, the humoral and cellular immune responses. DNA vaccines have been tested in a series of animal models, including experimental infections in mice and primates [20] and [25]. Recently, there has been a remarkable effort on the development of DNA vaccines because they are safe, induces fewer side effects than the live attenuated vaccines, can be administered to immunocompromised individuals, are cheap to manufacture, and need low infrastructure for maintenance [26].

Certain subgroup analyses, especially those examining regional differences, consisted of only 1 study in each region and thus should be interpreted with caution. The majority of study participants were younger than 7 years of age; only one single-season study presented www.selleckchem.com/products/Bleomycin-sulfate.html data for children and adolescents 7–17 years of age. However, LAIV efficacy in children and adolescents has not

been shown to vary as a function of age or pre-existing immunity to influenza [28]. Consistent with the previous meta-analysis by Rhorer et al., the present analysis used a fixed effects rather than a random effects model. A random effects model would be more appropriate if vaccine efficacy was assumed to differ among trials. However, the small number of trials available could result in a substantial Type I error rate [30]. Because the objective

of the current analysis was to provide a weighted average of vaccine efficacy estimates across multiple studies, a fixed effects model is more appropriate. In children 2 through 17 years of age, LAIV has demonstrated high efficacy after 2 doses in year 1 and after revaccination with a single dose in year 2. Efficacy was similar for A/H1N1, A/H3N2, and B strains. LAIV demonstrated greater efficacy compared with TIV in all 3 studies comparing the 2 vaccines. LAIV efficacy estimates relative to placebo and TIV for children from Europe, the United States, and Middle East were robust and were similar to or higher than those Epacadostat concentration observed in the overall population. This meta-analysis provides more precise estimates of LAIV efficacy among the approved pediatric age group and should provide reassurance regarding the routine use of LAIV in eligible children 2 years of age and older. This project was sponsored by MedImmune, LLC, a subsidiary of AstraZeneca. Drs. Ambrose

and Wu are MedImmune employees. Drs. Knuf and Wutzler have participated in an advisory board for AstraZeneca Dichloromethane dehalogenase and Dr. Knuf has lectured for AstraZeneca. Editorial assistance in developing this manuscript was provided by John E. Fincke, PhD, and Gerard P. Johnson, PhD, of Complete Healthcare Communications (Chadds Ford, PA) and funded by MedImmune. “
“On 25 April 2009 the World Health Organization (WHO) reported the emergence of a new influenza (H1N1) virus detected in North America [1]. This virus rapidly disseminated globally leading to the declaration of the first pandemic of the twenty-first century [2]. While the pandemic had moderate severity [3] and [4], specific risk groups appeared to have increased risk of morbidity and mortality, including pregnant women and individuals with chronic medical conditions [5], [6], [7], [8] and [9]. Vaccination is the most effective preventive measure against influenza [10] and [11], but the time required for influenza vaccine production meant that countries had to mitigate the first pandemic wave without a vaccine.

The correlation between the antibody concentration in sera and intestinal washes in each animal was performed calculating the Pearson’s correlation coefficient r. The lymphoproliferative response between groups was analyzed using one-way

ANOVA and Tukey’s post test. Statistical significance was defined as P ≤ 0.05. Graphpad 4.0 software was used for analysis. Vi-specific serum http://www.selleckchem.com/products/ON-01910.html antibodies were assessed in mice subcutaneously immunized with Vi-CRM197, unconjugated Vi, free CRM197 or PBS. Two weeks after priming (day 13), both Vi-CRM197 and Vi immunized mice developed a significant serum Vi-specific IgM response with a geometric mean titer [GMT] of 1280 and 425 respectively (P < 0.001 versus PBS immunized mice; Fig. 1A and Table S1). IgM titers induced by the glycoconjugate were significantly higher than those observed in Vi immunized mice (P < 0.01) ( Fig. 1A and Table S1). After boosting, Vi-specific IgM significantly selleck kinase inhibitor decreased (P < 0.05) while IgG significantly increased in Vi-CRM197-immunized mice (GMT of 1689 after priming [day 13] and of 4560 after boosting [day 24], P < 0.01) and persisted until day 60 with titers

significantly higher compared to mice immunized with Vi or CRM197 alone (P < 0.001; Fig. 1B and Table S2). In Vi-immunized mice the IgG response did not significantly increase after boosting, and persisted up to day 60 with a GMT of about 256 (P < 0.001 versus

PBS and CRM197 groups; Fig. 1B and Table S2). The IgG response detected in mice immunized only with Vi-CRM197 was about 8 times higher than that induced by unconjugated polysaccharide Vi after the primary immunization and about 18 times higher after boosting. These data demonstrate that the glycoconjugate was more efficient in stimulating antibody isotype switching. The analysis of Vi-specific serum IgG subclasses 10 days after boosting (day 24) showed a predominance of IgG1 in mice immunized with Vi-CRM197 (P < 0.001 versus other subclasses; Table S3) that were significantly higher than those observed in mice immunized with Vi antigen alone (P ≤ 0.001; Fig. 1C). These data corroborate the IgG subclass switch observed with other polysaccharides, such as pneumococcal and meninogococcal polysaccharides and their respective conjugate vaccines [13], [14] and [15]. No significant levels of serum Vi-specific IgA were detected in any group. Mice immunized with Vi-CRM197 developed a CRM197-specific serum IgG response with a subclass distribution similar to that observed for anti-Vi IgG (data not shown). This work therefore shows that boosting with Vi-CRM197 induces a significant increase of serum IgG typical of secondary antibody response to T-dependent antigens, and a dominance of the IgG1 subclass.

However, the reduction in frequency was significantly greater in the experimental PI3K inhibitor group, by a mean of 1.2 cramps per night (95% CI 0.6 to 1.8). The severity of nocturnal leg cramps did not improve at all in the control group. However, there was a substantial reduction in the experimental group. The mean difference in improvement in the severity of the nocturnal leg cramps was

1.3 cm on the 10-cm visual analogue scale. No adverse events were reported in either group. Our results showed that six weeks of nightly stretching of the calf and hamstring muscles significantly reduced the frequency and severity of nocturnal leg cramps in older people. The best estimate of the average effect of stretching on the frequency of cramps was a reduction of about one cramp per night. Given that participants had an average of approximately three cramps per night at the beginning of the study, this is a substantial effect and approximately equal to the effect we nominated as worthwhile. Since the stretches are quick and simple to perform, some patients may even consider the weakest effect suggested by Capmatinib price the limit of the confidence interval (a reduction of 0.6 cramps per night) to be worthwhile. The stretches reduced the severity

of the pain that occurred with the nocturnal leg cramps by 1.3 cm on a 10-cm visual analogue scale. We do not know the smallest effect on the severity of the cramps that patients typically feel would make the stretches worthwhile. In other research using the 10-cm visual analogue scale for pain, a change score of 2 cm has been proposed in chronic low back pain patients (Ostelo and de Vet, 2005). An effect of this magnitude was not achieved in our study within the 6-week intervention period. However, the confidence interval around this result is reasonably

narrow. Therefore patients can be advised that the average effect of the stretches is to reduce the severity of the pain by 1.3 cm on the 10-cm scale (or close to this value). Patients can then decide for themselves whether this effect – in addition to the reduced whatever frequency of the cramps – makes the stretches worth doing. In this trial, stretching was performed at home and was patient-centred. This facilitated performance of the intervention, which may have aided adherence with the stretches and increased the effectiveness of the intervention. In this setting, however, correct execution of the stretching technique was not closely monitored. All the participants in the experimental group did two exercises, regardless of whether the cramp was located in the hamstrings or calf. Greater effects may perhaps be achievable if stretches were to be targeted at the site(s) of each participant’s cramps. This could be investigated in a future trial.

The following section reviews anatomical and physiological characteristics of the LC-NE system that have implicated the system in stress. More detailed information about this system and its other putative functions that are outside the scope of this review can be found in (Aston-Jones et al., 1995; Foote et al., 1983; Berridge and Waterhouse, 2003). The LC is a compact cluster of NE neurons in the pons that serves as the primary source of brain NE (Grzanna and Molliver, 1980). A distinguishing anatomical feature

of the LC is its widespread, highly collateralized projection system that innervates the entire neuraxis (Aston-Jones et al., 1995 and Swanson and Hartman, 1976). Through this axonal system the nucleus LC can broadly influence neuronal activity Cell Cycle inhibitor throughout the brain. Notably, the LC serves as the primary source of NE in forebrain regions such as the hippocampus and cortex that govern cognition, memory and complex behaviors. Selleckchem Fulvestrant The physiological characteristics of LC neurons have been studied in vivo in rodents and non-human primates and in vitro in slice preparations and have implicated this system in arousal, attention and behavioral flexibility (Aston-Jones and Bloom, 1981a, Aston-Jones and Bloom, 1981b, Foote et al., 1980, Williams and Marshall,

1987 and Aston-Jones and Cohen, 2005). LC neurons discharge spontaneously and their tonic rate is positively correlated to arousal state (Aston-Jones and Bloom, 1981b and Foote et al., 1980). However, the relationship between neuronal activity and arousal is more than just correlation because selective activation or inhibition of LC neurons results in cortical and hippocampal electroencephalographic (EEG) activation or inhibition, respectively, indicating causality between LC discharge rate and arousal (Berridge and Foote, 1991 and Berridge et al., 1993). As described below, LC activation is necessary for cortical EEG activation by stress (Page et al., 1993). In addition to spontaneous firing, Dichloromethane dehalogenase LC neurons are phasically activated

by salient, multimodal stimuli that elicit a burst of discharge followed by a period of inhibition (e.g., Fig. 1) (Aston-Jones and Bloom, 1981a), (Aston-Jones and Bloom, 1981a and Foote et al., 1980). The phasic response precedes orientation to the eliciting stimuli, suggesting that the LC-NE system redirects attention towards salient sensory stimuli. LC neurons are thought to discharge synchronously during phasic activation as a result of electrotonic coupling through gap junctions between dendrites outside of the nucleus, in the peri-coerulear (peri-LC) region (Ishimatsu and Williams, 1996). In contrast, during spontaneous or tonic LC discharge, the neurons are thought to be uncoupled (Usher et al., 1999).

MERS-S1) as vaccine candidates and investigate their ability to induce neutralizing immune responses in mice. Moreover, to demonstrate the feasibility selleck inhibitor of using of a human adenovirus 5 based vaccine in dromedary camels, we have evaluated the infectivity and the presence of anti-adenovirus 5-neutralizing antibodies in this animal species. The MERS-S (GenBank JX869059) gene was codon-optimized for optimal expression in mammalian cells using the UpGene codon optimization algorithm

[40] and synthesized (GenScript). pAd/MERS-S was generated by subcloning the codon-optimized MERS-S gene into the shuttle vector, pAdlox (GenBank U62024), at SalI/NotI sites. The coding sequence for MERS-S1 (amino acids 1 to 725 of full-length MERS S, according to the GeneBank database) was amplified by polymerase chain reaction and inserted into the shuttle vector (Fig. 1A). Subsequently, replication-defective human adenovirus serotype 5, designated as Ad5.MERS-S and Ad5.MERS-S1, were generated by loxP homologous recombination and purified and stored as described previously [26], [41] and [42]. For detection of MERS-S

protein expression in A549 cells (human lung adenocarcinoma epithelial cell line) infected with five multiplicity of infection (MOI) of AdΨ5, Ad5.MERS-S, or Ad5.MERS-S1, cells were fixed with cold methanol 36 h following SB203580 in vitro infection and were incubated with pooled mouse sera against adenoviral vaccines. After washing, the cells were incubated with horseradish peroxidase-coupled anti-mouse secondary antibody (Invitrogen) and the MERS-S protein was

visualized by Avidin/Biotin Complex solution (Vector). BABL/c mice were inoculated intramuscularly (i.m.) with 1 × 1011 viral particles (v.p.) of Ad5.MERS-S, Ad5.MERS-S1, or AdΨ5 control, respectively. Three weeks after Chlormezanone the primary immunization, mice were boosted intranasally (i.n.) with the same dose of the respective immunogens. For the immunization study, a protocol approved by the University of Pittsburgh Institutional Animal Care and Use Committee was followed. Three weeks after prime immunization, pooled sera were obtained from all mice and screened for MERS-S-specific antibodies using fluorescence-activated cell sorter (FACS) analysis of Human Embryonic Kidney (HEK) 293 cells transfected with either pAd/MERS-S or pAd control using Lipofectamine 2000 (Invitrogen). After 24 h at 37 °C, cells were harvested, trypsinized, washed with phosphate buffered saline (PBS), and stained with mouse antiserum against Ad5.MERS-S, Ad5.MERS-S1, or AdΨ5 followed by a PE-conjugated anti-mouse secondary antibody (Jackson Immuno Research). Data acquisition and analysis were performed using LSRII (BD) and FlowJo (Tree Star) software. Sera from the animals were collected every week and tested for S protein-specific IgG1 and IgG2a by conventional enzyme-linked immunosorbent assay (ELISA). Briefly, A549 cells were infected with 10 MOI of Ad5.MERS-S1.

En France, parmi les 315 femmes enceintes ou en post-partum du registre établi lors de la pandémie de 2009, les césariennes et les accouchements prématurés étaient plus fréquents parmi les click here cas les plus graves, tout comme les nouveau-nés avec un plus faible poids de naissance [16]. Pour autant, il n’a pas été noté un excès de décès chez les nouveau-nés selon que les patientes étaient hospitalisées ou non [16]. Lors de cette

même pandémie de 2009, un nouveau-né né par césarienne d’une mère infectée, a développé une toux sèche. Une PCR pratiquée quatre heures après sa naissance était positive pour le virus A (H1N1) pdm09, confirmant une probable transmission prénatale du virus grippal [26]. Dans l’étude de cohorte prospective française il n’a pas été observé d’impact de l’infection grippale H1N1 sur l’issue de grossesse mais le nombre de cas de grippe était très faible [17]. En dehors d’un contexte pandémique, il n’existe actuellement pas de recommandation spécifique concernant la prise en charge d’une grippe en cours de grossesse. Devant un syndrome grippal avec une bonne tolérance clinique, en

l’absence de signe de gravité et de comorbidité, le diagnostic virologique n’est pas recommandé de façon systématique en contexte épidémique saisonnier. Une évaluation du bien-être fœtal par un enregistrement cardiotocographique et une échographie pourra être proposé à partir de 25 semaines d’aménorrhée (SA). L’examen obstétrical doit permettre de s’assurer de l’absence de menace d’accouchement learn more prématuré associée et écarter les diagnostics différentiels devant toute fièvre en cours de grossesse : une infection à Listeria en raison de sa gravité et une pyélonéphrite en raison de sa next fréquence. En pratique, un bilan comprenant une numération sanguine, un dosage de la C-reactive protein, au minimum une série d’hémocultures sur milieu aérobie et anaérobie et un ECBU sera réalisé comme

devant toute fièvre en cours de grossesse. Un traitement antibiotique probabiliste dirigé contre la Listeria (amoxicilline ou érythromycine en cas d’allergie à la pénicilline) doit être institué dans l’attente de la négativité des examens bactériologiques. Un traitement symptomatique antipyrétique sera adjoint avec une surveillance à domicile de la bonne évolution clinique. En cas de signes respiratoires sévères ou de comorbidité, un prélèvement nasopharyngé sera réalisé pour rechercher le virus de la grippe et instituer, le cas échéant, un traitement spécifique par oseltamivir (Tamiflu® 75 mg × 2 par jour per os pendant cinq jours) (avis du Haut conseil de la santé publique du 9 novembre 2012, http://www.hcsp.fr/docspdf/avisrapports/hcspa20121109_antivirauxextrahospgrippe.pdf). Les données disponibles sont en faveur d’une bonne tolérance de l’oseltamivir en cours de grossesse [27].

Transcribed ssRNA molecules were mixed in precise equimolar amounts. This dsRNA was adjusted to 7.2 × 107 copies/μl. Serial ten-fold dilutions of the standard RNA were included in each this website assay. Cycle Threshold (Ct) values were plotted against the serial dilutions of the standard RNA to produce the standard curve to determine the genome copies per ml of blood

sample. All horses were sero-negative at the beginning of the study and developed serum VNAb upon inoculation with MVA-VP2(9). No adverse reactions to vaccination were seen, other than a transient inflammation at the injection site which subdued after 24 h. On day 34 of the study, the vaccinated horses and 3 unvaccinated controls were challenged with AHSV-9. Following challenge with AHSV-9, all vaccinated animals remained clinically normal and their rectal temperatures remained within physiological ranges until the end of the study (Fig. 1). In contrast, all the control horses developed clinical signs consistent with the cardiac form of African horse sickness. They became febrile by day 2 post-infection as rectal temperatures reached values ranging between 39.08 to 39.28, a significant rise compared with the vaccinated group (Wilcoxon rank sum test: P = 0.05). These temperatures

peaked on day 3 (horse C3) and day 4 (horses C1 and C2), and then declined in the hours before death. Clinical signs in BI 6727 price the control animals were present by day 3 post-infection and comprised: mild general malaise and depression; palpebral oedema and conjunctivitis; and mild nasal Cell press discharges. These clinical signs slightly worsened

on day 4 and progressed very rapidly thereafter. The three control horses died between the end of day 5 (C3) and day 6 (C1 and C2). The post-mortem lesions of control horses were consistent with the cardiac form of AHS, and included: oedema, congestion and haemorrhages of the ocular conjunctiva; the presence of a yellow gelatinous oedema in the inter-muscular fasciae of the neck and sub-scapular region, oesophagus and epicardial surfaces; hydropericardium; hydrothorax; sub-endocardial haemorrhages; and congestion of the kidneys, liver, spleen and stomach mucosa. The lungs presented mildly enlarged interlobular septi but the typical frothy fluid of the ‘pulmonary form’ of AHS was not present. The results of these tests are presented in Table 1 and Table 2. All vaccinated animals were negative for infectious virus in blood whereas the control horses developed viraemia with viral titres that ranged between 104.5 to 104.6 TCID50/ml on day 3, and between 105.5 to 105.8 TCID50/ml on day 5. The differences between vaccinates and controls on each day were statistically significant (Wilcoxon rank-sum test: P = 0.03 for both days) Real time RT-PCR results indicate that there were significant differences in the viral load between vaccinates and controls. The mean viral RNA log10 copy number on day 3 was 106.8 for controls and 102.

It is known that influenza viruses isolated and propagated in mammalian cells often remain genetically and antigenically closely related to the virus present in clinical specimens [26], [27] and [28]. Isolation in embryonated hens’ eggs and also in cells can lead to amino acid changes in the hemagglutinin, which can occasionally alter antigenicity rendering the isolates unsuitable as candidate vaccine viruses [29], [30] and [31]. Cell culture isolates may thus increase the number of viruses available for vaccine virus selection and regulatory authorities are willing consider such viruses for the production

of influenza vaccines [24] and [32]. In the present study we evaluated the performance of vaccine manufacturing cell lines [12], [14], [15], [17], [33] and [34] for Selleckchem Bortezomib primary virus isolation from clinical specimens and analyzed the antigenic stability and antigen yields of resulting isolates in pilot-scale manufacturing processes. This

study was designed to serve two purposes. Cell lines used by vaccine manufacturers were evaluated for their permissiveness to isolate influenza viruses from clinical specimens. Genetic and antigenic stability, as well as the growth-characteristics of the isolates, were monitored Selleck DAPT in the homologous cell line and in those used by other manufacturers. Fig. 1 shows the 4 main experimental steps and the 3 critical performance parameters of this study. Twenty influenza virus-positive respiratory samples from patients with influenza-like Terminal deoxynucleotidyl transferase illness were included. These samples were collected in the USA or in Finland during the 2007–2008 and 2008–2009 influenza seasons. Four groups of five specimens were selected to represent each of the seasonal influenza subtypes: A(H1N1) viruses, A(H3N2) viruses,

influenza B viruses representing the Yamagata lineage and the Victoria lineage. Each original specimen was divided into 10 aliquots and stored at −80 °C until used for further experiments. Three different Madin-Darby canine kidney cell lines (MDCK-1[14] and [15]; MDCK-2[12], [14] and [33]; MDCK-3[33]) and one African green monkey cell line (VERO [17]) were used in the experiments. The MDCK-1 and MDCK-2 as well as the VERO cell lines were anchorage-dependent; whereas the MDCK-3 line was cultivated in suspension. The three MDCK cell lines were used for primary isolation of influenza viruses from clinical specimens and for pilot-scale virus production. The VERO cell line was used for small-scale production experiments, one representative isolate from each of the four virus groups (H1N1, H3N2, B-Victoria, B-Yamagata) was used. For production, MDCK-1 was grown on micro-carriers in serum free medium to which a protease was added to facilitate virus replication. Virus was harvested when cytopathic effect (CPE) was observed in all cells.

Furthermore, the overall majority of H7 vaccines in the pipeline are focused on egg-based production which might be an inadequate platform in a pandemic setting due to limited manufacturing capacities and longer production times compared to cell-culture based systems. Based on predictions that consider the current maximum global capacity

for influenza virus vaccine CHIR-99021 price manufacturing vaccine production will be too slow to adequately meet the needs for a vaccine in the event of a pandemic [36]. A major factor limiting the manufacturing capacity of a vaccine is the minimum immunogenic antigen dose that confers protection. It is highly desirable to obtain good efficacy already with low vaccine doses and the fewest possible injections to prevent shortages. Development of more efficient vaccines is a key objective defined by the Global Action Plan for Influenza vaccines by the WHO [37]. Here, we chose to evaluate a low-dose single-shot

VLP vaccine against the novel H7N9 virus. Single immunisation with as low as 0.03 μg SH1-VLP preparation (based on HA content) could confer full protection against a stringent homologous challenge (100 mLD50) in BALB/c mice (Fig. 1C). Mice that were vaccinated with a single vaccine dose of 3 μg SH1-VLP did not show any sign of disease. This is in contrast to an earlier study by Smith et al. who reported that mice vaccinated selleck chemical with a two dose regimen with 0.7–2 μg lost 10–15% of their initial body weight after a 3.5 LD50 challenge [14]. Since the VLPs used in their study were highly purified we would speculate that active baculovirus contaminants

in our vaccine preparations (supplementary data) acted as an adjuvant and boosted the immune response – an effect that was reported before. It was shown that baculovirus can enhance immunogenicity of VLP vaccines through boosting the immune response by interferon-signalling Ribonucleotide reductase and biasing IgG isotype distribution [16]. Vaccination with VLPs harbouring an HA from a closely related (but phylogenetically distinct) H7 strain, A/Anhui/1/13, also protected mice from PR8:SH1 challenge after only one immunisation. Generally, T-lymphocytes have long been appreciated as a critical contributor to protection and recovery from influenza infection [38]. Essentially, CD8+ T-cells play an important role in the clearance of virus infected cells and thereby limit viral replication, disease development and reduce mortality [26], [38] and [39]. We tended to address the importance of the cytotoxic immune response mediated by CD8+-cells in our challenge experiment. CD8+-depleted mice were fully protected in the challenge experiment and showed similar weight loss kinetics as observed for non-depleted mice (Fig. 1B and D), which is in agreement with previous findings [40]. However, in a recent work by Hemann et al.