All participants gave written informed consent before data collection began. Competing interests: The authors declare no conflict of interest related to this work. Support: This study is funded by a partnership grant from the National Health and Medical Research Council

Australia (ID 541958). The authors would like to sincerely thank Dr Dennis Wollersheim for his contribution in assisting with activity monitor data extraction. “
“The dose-response relationship between intensity of therapy and increased recovery of motor function after stroke is well supported by evidence Ku-0059436 mw (Kwakkel et al 2004, Galvin et al 2008, Cooke et al 2010), and is reflected in clinical guidelines for stroke rehabilitation (National Stroke Foundation, 2010), although the effect size of this benefit varies between individual studies (Kwakkel et al 2004, Galvin et al

2008). Despite this evidence, many observational studies have shown that people with stroke spend very little time engaged in physical activity during the course of a day in rehabilitation, with therapy sessions being the most active part of the day (Ada et al 1999, Bernhardt et al 2004). Therefore, physiotherapists working in stroke rehabilitation are constantly challenged to maximise the amount of active therapy stroke survivors are engaged in each day. In order to change clinical behavior it is important to www.selleckchem.com/products/ulixertinib-bvd-523-vrt752271.html be able to assess the existing behaviour or practice accurately. Only two studies have specifically examined the accuracy of therapists in reporting therapy time (Wittwer et al 2000, Bagley et al 2009), both of which used video-recordings of therapy sessions as the criterion standard. In an observational study embedded in a clinical trial of stroke rehabilitation, Bagley et al (2009) found that physiotherapists systematically overestimated the duration of therapy sessions by more than 20 per cent. In an earlier study, Wittwer et al (2000) found moderate to high correlations (Spearman from rank order correlation

coefficient 0.49 to 0.83) between therapist estimates and video-recorded time for subcategories of physical activity (upper limb, bed mobility, sitting, sit to stand, standing, and early gait activities), but the presence of systematic over- or under-estimations was not examined. Both of these studies investigated the accuracy of individual therapy sessions. The accuracy of therapists in estimating therapy duration for group circuit class therapy sessions has not been examined. The Circuit Class Therapy for Increasing Rehabilitation Intensity of Therapy after Stroke (CIRCIT) trial is a multicentre randomised trial currently investigating alternative models of physiotherapy service provision (Hillier et al 2011).

Gln exits from the end feet and is untaken by Gln transporters, present on the juxtaposed abluminal membrane of capillary endothelial cells (Lee et al., 1998). Once into the endothelial cell, Gln is converted back to Glu via the endothelial glutaminase, which now diffuses into the blood by facilitative transport. Such a mechanism could also sub-serve a neurometabolic coupling (Jakovcevic and Harder, 2007). Under pathological conditions involving a brain insult such as ischemic stroke, traumatic brain injury or prolonged epileptic seizures, Glu is uncontrollably released from its neuronal and glial stores, via the reverse

operation of the excitatory amino acid transporters (EAATs) (Vesce et al., 2007). In these circumstances, excess Glu is also regulated by the transporters associated with the ubiquitous and dense network of brain capillaries, leading to excitotoxic neuronal death AT13387 in vivo in very large brain territories. One of the most severe acute neurological conditions, associated with excessive Glu release, is the status epilepticus (SE). SE is

defined as an epileptic seizure lasting more than 30 min or as intermittent seizures, lasting for more than 30 min, during which the patient does not recover consciousness between repeated episodes ( Leite et al., 2006). SE is one of the most common neurological emergencies and several prospective studies have reported an incidence of 10–20/100,000 amongst whites in Europe and the US ( Hesdorffer et al., 1998, Coeytaux et al., 2000 and Knake et al., 2001). Convulsive SE is the MLN8237 commonest form, representing 40–60% of all SE cases. Mortality is high, with one out of five dying in the first 30 days ( Logroscino et al., 1997). The main neurological sequels of SE reported in the literature are cognitive impairment, brain damage-related Montelukast Sodium deficits, and long-term development of recurrent seizures ( Leite et al., 2006). Neurobiological substrate of SE-related brain damage includes the excitotoxic effect of excitatory amino acids, particularly Glu (Ben-Ari and Schwarcz, 1986, Choi, 1988 and Naffah-Mazzacoratti and Amado, 2002). Intense seizure activity

causes massive Ca2+ influx, which results in increased intracellular and intra-mitochondrial membrane depolarization, superoxide production and activation of caspases (Gupta and Dettbarn, 2003, Persike et al., 2008 and Henshall, 2007). The large increase in cytosolic Ca2+ evoked by activation of Glu receptors (NMDA and AMPA/kainate) seems to be a necessary step in the overall process of neuronal degeneration. This process triggers the acute neuronal cell death that occurs after SE (Maus et al., 1999, Fujikawa et al., 2000 and Men et al., 2000). Gottlieb et al. (2003) recently tested the hypothesis that a larger Glu concentration gradient between ISF/CSF and blood plasma could provide an increased driving force for the brain-to-blood Glu efflux.

Nazarov HKI272 and Zilinsky (1984) reported that stretch exercises with vibration gave a greater increase in simple clinical measures of flexibility than stretch exercises alone. In a more recent study, Fagnani and colleagues (2006) demonstrated that whole body vibration also may increase flexibility alone without any further stretching exercises. These studies were focused on athletic subjects and showed enhancement of athletes’ flexibility as a result of vibration in both short-term and long-term protocols. However, further investigations

examining the passive mechanical properties of muscles are required to determine whether the changes are due to true alterations in muscle ‘length’. The underlying Pazopanib manufacturer mechanisms of the effect of vibration on flexibility might involve a shift of the pain threshold and the stimulation of muscle spindle and Golgi tendon organs, causing the inhibition of the contraction (Issurin et al 1994), which involves neural circulatory and thermoregulatory factors (Mester et al

1999). Vibratory stimulation of the muscle spindle may produce Ia input, which modulates the recruitment thresholds and firing rates of motor units. Issurin (2005) has proposed that vibration enhances excitatory inflow from muscle spindles to the motor neuron pools and depresses the inhibitory impact of Golgi tendon organs due to accommodation to vibration stimuli. Ribot-Ciscar and colleagues (1998) demonstrated that after tendon vibration, a stretched muscle was perceived as being less stretched than it actually was, which indicates that vibration produces centrally these localised neural changes. They demonstrated

that the static stretch sensitivity of the muscles was decreased during the 3 sec following vibration exposure, due to a decreased spontaneous firing rate in the muscle spindle primary endings after vibration. This may contribute to the increased flexibility after vibration. The level of Golgi tendon organ excitation is therefore a possible mechanism for the muscle flexibility after vibration (Bosco et al 1999, Issurin et al 1994). Lundeberg and colleagues (1984) showed that the application of vibration to muscles produces analgesic effects during and after the procedure. This may delay the start of pain, which serves as a natural barrier to muscle elongation techniques, although it was shown that vibration has no effect on the pain perception in the vibrated muscles (Sands et al 2008). The use of vibration in pathological conditions such as muscle shortening remains an exciting area for further research. However, research in these fields is in its early stage. Much research is still needed on the optimal frequencies, amplitudes, and vibration durations to improve each of these factors. More studies are also needed to provide further knowledge about the optimal frequency and progression of the vibration.

This example highlights the importance of driving higher-order molecular structure in modern vaccines. The major vault protein (MVP) is another kind of self-assembling protein. Ninety-six units of MVP can self-assemble into a barrel-shaped vault nanoparticle, with a size of approximately 40 nm wide and 70 nm long [127]. Antigens that are genetically fused with a minimal interaction domain can be packaged inside vault nanoparticles by self-assembling process when mixed with MVPs [127]. Vault nanoparticles

have been used to encapsulate the major outer membrane protein of Chlamydia muridarum for studies of mucosal immunity [127]. Another type of nanoparticles used as adjuvants in vaccines delivery is nano-sized emulsions [100], [128] and [129]. These nanoparticles can exist as oil-in-water or water-in-oil forms, where the droplet size can vary from 50 nm to 600 nm [128]. Doxorubicin ic50 Emulsions can carry antigens inside their core for efficient vaccine delivery [128] or can also be simply mixed with the antigen. One

commonly-used emulsion is MF59™, an oil-in-water emulsion which has been licensed as a safe and potent vaccine adjuvant in over 20 countries [35] and [130]. It has been widely studied for use in influenza vaccines [130], [131] and [132]. Another is Montanide™, a large family of both oil-in-water and water-in-oil emulsions, including ISA 50 V, 51, 201, 206 and 720 [35] and [133]. Montanide ISA 51 and 720 have been used in Malaria vaccines [134] and [135], Montanide ISA 201 Bcl2 inhibitor and 206 have been used in foot-and-mouth disease vaccines [136]. Recently, a tailorable nano-sized emulsion (TNE) platform technology has been developed using non-covalent

click self-assembly for antigen and drug delivery [137] and [138]. An oil-in-water nanoemulsion is formed using designed biosurfactant peptides and proteins. Using a self-assembling peptide-protein system, immune-evading PEG and a receptor-specific antibody can be arrayed in a selectively proportioned fashion on the aqueous interface of a nano-sized oil-in-water emulsion (Fig. 4). Targeted delivery of protein antigen to dendritic cells was achieved [138]. This work demonstrates Adenylyl cyclase a new and simple way to make biocompatible designer nanoemulsions using non-covalent click self-assembly by sequential top-down reagent addition. Vaccine formulations comprising nanoparticles and antigens can be classified by nanoparticle action into those based on delivery system or immune potentiator approaches. As a delivery system, nanoparticles can deliver antigen to the cells of the immune system, i.e. the antigen and nanoparticle are co-ingested by the immune cell, or act as a transient delivery system, i.e. protect the antigen and then release it at the target location [79]. For nanoparticles to function as a delivery system, association of antigen and nanoparticle is typically necessary.

Mycobacterial HSP65, which has about 50% homology with the human homologue HSP60 [38] serve as the carrier for the diabetogenic peptide P277, may interact with B cells. Recent studies show that HSPs enhance delivery and cross-processing of HSP-linked Ag by B cells [35] and [39]. Although the effects of antigen presentation by various antigen-presenting cells to cloned CD4+ T cells in vitro has not been tested in the present study, the idea has been

established that dendritic cells and macrophages promote antigen-specific Th1 cell differentiation, and B cell presentation of antigen usually induces T cell anergy and tends to promote naïve T cell differentiation toward an anti-inflammatory Th2 phenotype [40], [41], [42] and [43]. Interestingly, T cells from the HSP65-6 × P277 treated mice when incubated with P277 the pattern of cytokine showed an increase in IL-10 and a decrease in IFN-γ (Fig. 4). If activated P277-specific B cells PI3K cancer serve as APCs and present HSP65-6 × P277 to T cells, it might be promote antigen-specific

Afatinib mw Th2 cell differentiation. Moreover, the capacity of Th2 cells to function as T-helper cells for antibody production is severely hampered in the control mice, which recruited lower levels of P277-specific B cells than HSP65-6 × P277 treated mice (Fig. 1). It is conceivable that the absence of P277-specific B cells to act as antigen-presenting cells may be responsible, in part at least, for the decrease of Th2 cell differentiation in the HSP65 and P277 treated mice. In this study, the mice immunization with the fusion protein HSP65-6 × P277 elicited much higher levels of Th2-type cytokines and lower Th1-type cytokines than the control mice (P < 0.05). A possible explanation for the enhanced Th2-regulated immune response in HSP65-6 × P277 treated mice is that when P277-specific B cells are recruited, the dramatic increase in levels of IL-4 or other Th2-type cytokines. This occurs by the modulation of

the homing of autoreactive cells to inflammatory sites and the stabilization of a protective Th2-mediated environment in the pancreatic islets ( Fig. 2 and Fig. 3). Thus, IL-4 favors the expansion of regulatory CD4+ Th2 cells in vivo that would normally be subject to promote retention of the Th2 phenotype. The respiratory tract is a less acidic until and proteolytic environment and it has been an attractive route of immunization. Nasal administration of autoantigen decrease organ-specific inflammation has been tested experimentally in several models of autoimmunity. For example, nasal administration of HSP65 in mice lacking the receptor for LDL can cause significant decrease in the size of atherosclerotic plaques, and suppress inflammation and atherosclerosis development [16]. Weiner HL et al showed that nasal administration of amyloid A-β peptide limits decreased amyloid plaque deposition in a transgenic animal model of Alzheimer’s disease [44].

It can be produced using safe and scalable conditions, without the need of growing live viruses and the disadvantages related to that. HA vaccines also allow for the use as marker vaccines, although this will depend also on other circulating influenza strains in the target population. Marker vaccines make it possible to serologically detect and monitor infections in a vaccinated GSK126 order population, allowing for the collection of invaluable epidemiological data. The advantage of recombinant HA trimers over recombinant HA monomers is that the former induce higher levels of neutralising antibodies

[20]. In part this is likely due to the fact that trimers mimic the natural membrane-bound structure, including the relevant epitopes to induce neutralising antibodies against. Trimeric HA preparations therefore seem more promising vaccine candidates than previously used HA monomers. Vaccination of pigs reduces the exposure of humans to the influenza virus almost completely. In case pigs are deemed a potential source of infection for humans, vaccination of herds at risk, or even the entire pig population, therefore seems a realistic option. The vaccine could however also

be used for humans themselves. Similar results with an HA trimer based on H5N1 in poultry and mice [21], but also ferrets [22], suggest that the use of these recombinant HA trimers is promising Z-VAD-FMK solubility dmso in general. In this experiment we used a rather high dose of HA as proof of principle for the soluble trimer. Further studies would need to determine the efficacy of the vaccine at lower doses. The lower the dose,

the easier it would be to produce sufficient quantities of vaccine in a short time, which is one of the most crucial issues during a pandemic or other emergency situation. Furthermore, it would make the vaccine more cost-affordable, which is especially relevant for continuous use of the before vaccine in pig herds, for instance for use of this kind of vaccines against swine influenza strains that are endemic. Contrary to previous inoculation studies with the H1N1v influenza virus [6], [7] and [8], no clinical symptoms were seen in the inoculated control animals. Nevertheless, virus titres from nasal and oropharyngeal swabs were higher than published before [7], and also relatively high virus titres were found in all parts of the lungs, providing sufficient evidence that the inoculation itself was successful. Furthermore, pathological changes, both macroscopic and microscopic, were abundantly present in the unvaccinated controls, while only some minor changes were seen in some of the vaccinated pigs. In our study the pigs were much older than in the other published studies. Whether this explains the lack of clinical symptoms, remains to be seen. In a previous study with swine influenza virus in naïve pigs, clinical symptoms seemed to be even more severe in older pigs [23].

Les modifications immunologiques induites par la grossesse peuvent être à l’origine d’une susceptibilité Selleckchem Perifosine accrue aux infections virales graves. Le système immunitaire, à travers ses deux principales composantes,

l’immunité cellulaire et humorale, doit en effet s’adapter à la greffe semi-allogénique que constitue le fœtus. Pour éviter le rejet du fœtus, plusieurs mécanismes physiologiques sont mis en œuvre. Ils font intervenir des mécanismes protecteurs propres et des adaptations de l’immunité innée et adaptative. La tolérance locale aux antigènes fœtaux, liée à un profil cytokinique gestationnel particulier d’immunotolérance Th2, pourrait entraîner un état de suppression de la réponse cellulaire au plan systémique [3]. Par ailleurs, l’interface materno-fœtale n’exprime pas les Complexes Majeurs d’Histocompatibilité de classes I et II conventionnels. La forte expression de HLA-G sur le cytotrophoblaste joue un rôle préventif local de l’activation des cellules NK maternelles. L’expression par le virus A/H1N1 d’antigènes « HLA-G like », pourrait expliquer la survenue de formes graves de grippe chez la femme enceinte [4]. Outre les modifications immunologiques, il existe lors de la grossesse des modifications hémodynamiques et respiratoires qui peuvent expliquer le risque accru de survenue de grippe grave. Il existe peu de données sur le passage transplacentaire du virus grippal [5] and [6]. Crizotinib manufacturer Des

travaux fœtopathologiques reposant sur quelques cas étudiés au deuxième trimestre de la grossesse ont été publiés : le virus grippal a été mis en évidence dans les cellules cytotrophoblastiques et dans les tissus pulmonaires et hépatiques fœtaux [5]. L’analyse histologique placentaire retrouve en conséquence de l’infection placentaire des infiltrats de fibrine et des lésions inflammatoires périvillositaires

[5]. D’autres auteurs font l’hypothèse que le passage transplacentaire de cytokines MTMR9 pourrait induire une défaillance mutiviscérale chez le fœtus [6], cependant cette hypothèse doit être prise avec réserve et faire l’objet d’investigations supplémentaires. En population générale, le taux d’attaque de la grippe est estimé selon les années entre 5 % et 10 % chez l’adulte [7], et serait de 5 et 22 % au cours de la grossesse [8] and [9]. Un excès de consultation pour infection respiratoire aiguë au cours des épidémies de grippe saisonnière a également été mis en évidence chez les femmes enceintes [10]. Au cours des travaux réalisés au niveau international, la grossesse est identifiée comme un facteur de risque de forme grave de grippe, même en l’absence de comorbidité [7], [9] and [11]. Ainsi, le risque d’hospitalisation pour complications au cours de la grippe est plus élevé chez la femme pendant la grossesse qu’en dehors de la grossesse [9] avec un risque augmenté d’un facteur entre 1,7 et 7,9 dépendant du trimestre de grossesse et des facteurs de risque associés [7] and [11].

The results depicted in Table 1, clearly indicated that all the dependent variables are strongly dependent on the selected independent variables as they shown wide variation among the 9 batches (F1–F9). The fitted equations (full

models) relating the responses to the transformed factor are shown in Table 2. The polynomial equations can be used to draw conclusions after considering Selleck Palbociclib the magnitude of coefficient and the mathematically expressed positive or negative. The high values of correlation coefficient for the dependent variables indicate a good fit. The influence of CS ratio (A) and amount of GA (B) on dependent variables were shown in response surface plot in Fig. 3 (a–d). optimized batch was identified Cyclopamine cost in the experimental design with constraints on dependent variables is shown in Fig. 3(e). The microspheres of all the batches were spherical, free flowing, discrete and uniform size under optical microscopy. Particle size ranges from 48.63 ± 0.47 to 62.31 ± 0.25 μm. The scanning electron micrograph (SEM) of microspheres (F7) is illustrated

in Fig. 1, utilized to observe the surface morphology which is uneven and some crystals scattered on the surface of microspheres contribute to a burst release and helps to achieve effective concentration quickly after oral administration. The swelling index, percentage mucoadhesion and drug entrapment efficiency ranges from 1.04 ± 0.25 to 2.12 ± 0.56, 62.39 ± 0.57 to 76.89 ± 0.91% and 46.33 ± 0.12 to 73.50 ± 0.27% respectively. Swelling studies indicated that with an increase in crosslinking, the swelling ability decreased. Extent of crosslinking exhibited an inverse relation to drug release rate as well as mucoadhesion, whereas CS concentration exhibited an inverse correlation with drug release rate and mucoadhesion. The results of multiple regression however analysis and F-statistics revealed that for obtaining sustained release, the microspheres should be prepared by using relatively lower level of GA and higher level of CS. The optimized formulation F7 which is more suitable for sustained release upto 12 h, follows zero order kinetics (R2 0.985), best fitted with Korsmeyer–Peppas

(R2 0.995) model and non-fickian diffusion (n value 0.735) dominates the drug release through the swellable matrix and hydrophilic pores. Drug- excipient compatibility studies reveals that no interaction between the CP and CS. Stability studies (F7) shows absence of appreciable changes in drug content and release which were stored at various temperatures, proved that stability of microspheres in normal storage condition. The X-ray photographs of in vivo mucoadhesive study were shown in Fig. 5. At 0 h, microspheres remains as such, after 3 h and 6 h it increases in size, proves the swelling ability of microspheres in gastric fluid and extensive mucoadhesion which helps for gastric retention. This observation reveals that chitosan microspheres are more suitable for gastroretentive system.

06 × 10−2/site/year (95% HPD 9.53 × 10−3 to 1.05 × 10−2). This is check details similar to the report (1.12 × 10−2/site/year) for VP1 sequences of A-Iran-05 viruses [13]; but higher than those reported by others [26], [27], [28], [29], [30], [31] and [32]. The high evolutionary rate of serotype A viruses in the ME is resulting in emergence of new variants in the region. An unbiased analysis of capsid sequences of the 51 A-Iran-05 viruses revealed 692 nt substitutions at 637 sites distributed

across the region (Fig. 1B). Out of these, 80.05% of nt substitutions were found to be synonymous (silent) and 19.95% were non-synonymous (non-silent). Forty seven sites were identified to have been substituted twice and four were substituted three times. At one site (VP2-134) the

first two bases of the codon were mutated encoding 5 different aa (P->T/S/L/H). This residue is located very close to residues VP2-132 and 133 that were reported as critical by mar-mutant studies for A10 virus [9]. In addition, the residue at this position has been reported to strongly influence the binding of antigenic site-2 mAbs in serotype O viruses [16]. Out of the four Pictilisib purchase sites with three nt substitutions (encoding 2–4 aa residues), three were present in VP3 and one in VP1 (Table 1A). The analysis of the capsid aa residues of A-Iran-05 viruses revealed 140 substitutions at 101 sites across the capsid (Fig. 2A) with some sites having 2–5 alternate aa (Table 1B). Interestingly, sequences for VP1-204 encoded five different aa and exhibited nt changes at all the three positions within the codon as did VP1-196, with changes at all the three positions of the codon giving rise to four alternative aa. In addition, the non-synonymous nt substitutions were not equally distributed across the capsid coding regions: there were several local areas where the dN/dS ratio was higher than in other parts of the sequence alignment

(Fig. 2B). One region in VP3 (57–65), two in VP2 (75–76 and 130–134) and eight regions in VP1 (52–53, 83–84, 92–105, 131–132, 137–141, 145–152, 168–171 and 192–204) had dN/dS ratio of >1 indicative of sites under strong positive selection. Investigation of aa variability Linifanib (ABT-869) across the capsid of the A-Iran-05 viruses revealed VP4 to be highly conserved and VP1 least conserved (Fig. 3A); similar to an earlier report [13]. The residues with a score greater than 0.75 (3 in VP2, 6 in VP3 and 12 in VP1) are shown in Fig. 3B-D indicating that over 50% of the residues with very high variability scores were present in VP1 (Fig. 3A). All these residues were found to be surface-exposed, except one residue in the N-terminus of VP1 (position 28) and one in N-terminus of VP3 (position 8) (Fig. 3C and D).

All adverse events (AEs) were coded according to the MedDRA adverse event dictionary (version 12.1) [27] and graded for severity using the FDA guidance document for the toxicity scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials [28]. Screening samples were assessed using standard, non-validated HAI assays at Duke-NUS Graduate Medical School. All further immunogenicity assessments on sera of recruited volunteers from baseline (Day 0), Day 21 and Day 42 were performed on blinded samples, under GLP conditions, using validated HAI Quizartinib price assays at Southern Research

Institute (Birmingham, AL). In addition to A/California/07/2009 (H1N1) cross-reactive immunogenicity against A/Brisbane/10/10 (H1N1) and A/Georgia/01/13 (H1N1) was tested. All virus strains were purchased from the Centers for Disease Control and Prevention (CDC; Atlanta, GA). An unblinded research coordinator randomly assigned subjects 1:1 to the adjuvanted or the non-adjuvanted group.

A computer-generated list (SAS® software, NC, USA) with randomly permutated block sizes of 4 and 6 was provided by SCRI. A sample size of 32 subjects per arm Epacadostat chemical structure was required to achieve the FDA criterion for seroconversion with a power of 80%, assuming an incidence of 65% [29]. To compensate for 20% drop-outs 40 subjects per arm were planned. The study was not powered to achieve the FDA criterion for seroprotection. The primary endpoint was seroconversion against A/California/07/2009 (H1N1) by HAI on Day 42, defined as either a pre-vaccination HAI titer <10 and a post vaccination HAI titer ≥40, or

a pre-vaccination HAI titer ≥10 and minimum four-fold rise in post-vaccination HAI titer. The co-secondary endpoint (with safety) was seroconversion on Day 21. In addition, geometric mean titers (GMT) and the percentage of subjects achieving seroprotection (HAI titer ≥40), Casein kinase 1 were calculated, the latter only for subjects with baseline HAI titers <40. Geometric mean titer fold rise (GMR) was calculated and GMT and GMR were compared between groups on log-transformed HAI titers using the two-sample t-test [30], [31] and [32]. The 95% CIs of GMT and GMR were constructed by exponential transformation of related 95% CIs based on the log-transformed HAI titer data. Values shown are for the modified Intention-to-treat (ITT) population, not including two subjects that withdrew consent prior to receiving the first dose. AEs and severe AEs were summarized by treatment group with each subject counted once per AE category with the highest severity of treatment emergent AE (Day 0-Day 42). Of 156 healthy volunteers consented and screened, 84 were randomized to the treatment groups and scheduled to receive adjuvanted (n = 43) or non-adjuvanted (n = 41) vaccine.