Conversely our adjustment for under-testing (adjustment factor 2) could over-estimate true incidence since it is possible that children who are not tested represent a different clinical spectrum of disease, making invalid the assumption that the proportion of influenza positive cases in the untested group is the same as in the BMS-754807 chemical structure tested group. We also did not make any adjustments for children readmitted to the same or different HA hospital with the same influenza infection and for possible nosocomial infections which could have led to an over-estimation of incidence. It is also likely that children with nosocomial influenza will have a longer length of stay, emphasising

that length of stay does not consistently reflect disease severity. We have also assumed that the adjustment factors derived from one institution, PWH, can be applied uniformly across all the HA hospitals, and that these factors are stable over time. Although PWH is one of the largest HA hospitals accounting for about 10% of all the public hospital paediatric admissions, it is possible that there may be differences in clinical practices, admission policies and laboratory services between PWH and other HA hospitals and also over time. Estimates of the incidence of influenza

that requires hospital admission were higher in children less than 5 years of age. Incidence per 100,000 person-years was particularly high for infants aged 2 months to below 6 months of age (1762) but lower in those below two months

of age (627). Overall these estimates are higher than our previous 1997–1998 estimates but similar GDC-0449 supplier to other Hong Kong estimates. Although a higher positivity rate for influenza was noted during the 2009/10 influenza surveillance period when A(H1N1)pdm09 started to circulate, this could reflect a permissive admission policy rather than increased disease burden and/or severity. Our data support the recommendation that effective vaccination of pregnant women is likely to have a significant impact on reducing disease burden in young infants below 6 months of age hospitalised for influenza. The Statistics and Workforce Planning Department in the Strategy and Planning Division of the Hong Terminal deoxynucleotidyl transferase Kong Hospital Authority provided the paediatric hospitals admission dataset from the HA clinical data repository for this study. Contributors: All authors approved the manuscript. E.A.S.N., M.I., J.S.T., A.W.M., P.K.S.C., contributed to study design and data interpretation. M.I. was the principal investigator. L.A.S. undertook literature review and initial drafting of manuscript. E.A.S.N., S.L.C., M.I., S.K.L., W.G., contributed to data analysis and interpretation. E.A.S.N. wrote the manuscript and produced all figures. Funding: This study was funded by the World Health Organization as part of Project 49 of the United States of America Center for Disease Control and Prevention, Grant 5U50C1000748.

Patients whose tumors were assay-resistant to carboplatin had an increased risk of early Alpelisib disease progression, as compared to those whose assay results were nonresistant for carboplatin, recurring on average 5 months sooner. Furthermore, based on the Kaplan-Meier plot of the current study (Figure 2), within 6 months of the start of chemotherapy, 25% of assay-resistant patients had already recurred, while <10% of assay-sensitive (nonresistant) had recurred. Likewise, at

18 months after the start of chemotherapy, approximately 50% of assay-sensitive patients had been free of disease progression, while 80% of assay-resistant patients had recurred. Multivariate analysis of assay results for paclitaxel demonstrated a positive trend, and, further, patients who were resistant to both agents demonstrated the worst outcomes, which was significantly different from patients nonresistant to both agents. These results are consistent with the notion that the platinum portion of the standard regimen for advanced-stage EOC plays the larger role in the clinical performance of that regimen.18 and 19 As such, it is expected that assay results

for paclitaxel are not as highly correlated with PFS as are those for carboplatin and carboplatin + paclitaxel. OS will be included in future analyses. The ability of this assay to identify patients likely to be platinum resistant creates the

opportunity to consider alternate treatments regimens for these patients earlier Selleck Saracatinib in the course of treatment. Alternate treatments may be considered either initially following surgery or upon first clinical indication of suboptimal performance during standard first-line treatment. Earlier intervention may allow for a reduction in toxicities incurred by the patient from ineffective therapy, as well as a reduction in the overall costs of treatment.20 Most importantly, assay-informed treatment decisions may lead to Parvulin earlier treatment with a more effective therapy, thereby delaying recurrence and potentially lengthening the overall expected survival duration for these high-risk patients. Identification of advanced-stage EOC patients as platinum resistant prior to treatment could inform first-line treatment decisions in a variety of ways, including substitution of alternate active agents, alteration of the planned first-line therapy to a dose-dense approach, or the addition of novel therapies that may overcome the resistance observed.5, 6, 7, 21, 22 and 23 Results from various completed and ongoing studies investigating alternate treatment strategies to carboplatin + paclitaxel should be referenced when considering treatment different than carboplatin + paclitaxel.

As elimination is approached, fewer and fewer infections will occur, perhaps making natural boosting of a protective immune response a less impactful attribute of a product’s TPP. Furthermore, expression in the human increases the possibility that immune selection will lead to the proliferation

of escape mutants. Additional data are therefore needed to support KU-55933 cell line whether endemic boosting should be a critical attribute of an ideal SSM-VIMT. The clinical development plan (CDP) and the basis of regulatory approval for an SSM-VIMT will likely be different from those applied to pre-erythrocytic and blood-stage malaria vaccines due to the methods in which vaccine effect will be established at the level of the community rather than the individual. In 2010, the major points of discussion on CDP/regulatory pathway were on the acceptability to regulatory authorities of a vaccine acting via delayed clinical benefit, the appropriate CDP and regulatory pathway, including the potential need for a cluster randomized trial (CRT), and the required level of efficacy. A buy Vorinostat critical

outcome of the 2010 MVI TBV workshop was that the US Food and Drug Administration (FDA) indicated that there is no legal bar to prevent a vaccine such as an SSM-TBV from being considered for licensure in the context of their review process. The FDA has the authority to license biological products that are demonstrated to be “safe, pure, and potent” (Section 351 of the Public Health Service Act & Section 505(b) of the Food, Drug, and Cosmetic Act), regardless of whether the disease occurs in the United States [23]. This feedback has encouraged the malaria vaccine development community to consider product development pathways for vaccine approaches exclusively targeting

parasite transmission from human to too mosquito. In 2012, moreover, the report on the MALVAC meeting states, “great progress has been made in recent years with a general acceptance in malaria vaccine circles that the issue of community benefits for TBV is not a major hurdle for clinical or regulatory pathways” [24]. The challenge moving forward will be to further define both the CDP and regulatory pathways and seek specific feedback from regulators, such as the FDA, European Medicines Agency, or another stringent regulatory authority. Another important outcome of the VIMT research agenda-setting meetings and consultations was the preliminary definition of two potential clinical development pathways for an SSM-VIMT (Fig. 1). One involves a large-scale, Phase 3 efficacy trial, which, in the case of an SSM-VIMT, has been proposed by regulators to be a CRT to demonstrate vaccine impact on incidence of infection in the community.

, 2001, Mikkaichi et al., 2004, Yamaguchi et al., 2010 and Taub et al., 2011). Abiraterone supplier Similarly, Rh123 has been described as a substrate for MRP1 (Hamilton et al., 2001), the Breast Cancer Resistance Protein (BCRP) (Doyle et al., 1998) and OCT (Masereeuw et al., 1997 and van der Sandt et al., 2000). The absence of vectorial transport of 3H-digoxin and Rh123 in RL-65 cell layers also indicates these other transporters may not be expressed or functional in the model. Transport studies were performed in RL-65 cell layers 8 days after seeding on Transwell® inserts. There is currently no standardised

time in cultures prior to permeability measurements in human bronchial epithelial cell layers and these are commonly conducted in 8–21 day old cell layers. However, there are indications in the literature which suggest transporter levels in pulmonary in vitro absorption models may be affected by the length in culture, with an optimal expression and activity achieved after 21 days ( Madlova et al., 2009, Haghi et al., 2010 and Mukherjee et al., 2012). Therefore, 8 days in culture may not have been sufficient for expression

of fully functional transporter systems in RL-65 selleckchem cell layers. In the culture conditions tested, the layers could nevertheless not be used for drug transport studies after 9–10 days on Transwell® as the TEER decreased to <200 Ω cm2 thereafter, before cells eventually detached from the filters. There is therefore a need to prolong the time these can be maintained at an AL interface. For instance, culture on different filter material or substrate coatings and optimisation of the medium composition may improve the usefulness of the model as a pre-clinical permeability screening tool. The RL-65 cell line was successfully grown at an air–liquid interface in a defined serum-free medium for 8 days. RL-65 layers exhibited suitable absorption barrier properties including TEER and paracellular permeability in the same range as established human bronchial epithelial models. Furthermore, they expressed transporters present

in the native epithelium, although their functional Oxygenase activity was not demonstrated. This initial study indicated that, following further optimisation of the culture conditions, RL-65 cell layers may offer a valuable in vitro model for permeability screening in rats and assist in the evaluation of interspecies differences in pulmonary drug absorption. This work was carried out under the Targeted Therapeutics, Centre for Doctoral Training at the University of Nottingham (Grants EP/D501849/1 and EP/I01375X/1) and AstraZeneca. This was funded by AstraZeneca, the Engineering and Physical Science Research Council (EPSRC, UK) and the University of Nottingham. The authors would like to thank François Spiertz, Fabrice Bayard and Natasha Tang for collection of preliminary data.

Non-reactive anti-HBs titers (<10 mIU/mL) were present in 46%

of vaccinated subjects and in all of the unvaccinated participants. A non-reactive anti-HBs titer was significantly associated with non-vaccination (p < 0.0001; OR 22.28; 95% CI 2.92–170.12), vaccine receipt between birth and 5 years of age, and receiving only 1 or 2 doses of the HBV vaccine ( Table Selumetinib mw 3). Older adults were more likely to have been vaccinated between the ages of 6 and 18 years and were more likely to have unsafe sexual risk factor (Table 4A). Receiving only 1 or 2 doses of the HBV vaccine was associated with having piercings or tattoos (Table 4B). Those men who received the HBV vaccine between the ages of 6 and 18 were more likely to have an incomplete vaccination Selleck INCB024360 schedule (p < 0.001; OR 5.13; 95% CI 2.05–12.84). Young men without a VC were more likely to be less educated, to be employed, to have less educated parents, and to have a lower household income (data not shown). In addition, adults without VCs were more likely to have undetectable anti-HBs titers (p < 0.0001; OR 2.51; 95% CI 1.64–3.82). Overall, 70% of the studied adults had been vaccinated and/or had

positive anti-HBs titers. Since the hepatitis B vaccine was included in the Brazilian National Immunization Program, there has been a substantial increase in vaccination coverage, especially among children and adolescents [3]. However, cases of hepatitis B have not appeared to decrease accordingly, probably due to long incubation and latency periods, the misdiagnosis of acute cases, and underreporting of disease [10]. Mandatory screening has reduced the transmission of HBV through blood transfusions, but sexual transmission remains a concern among unvaccinated adolescents and adults. This raises questions regarding the need to promote Suplatast tosilate vaccination through educational campaigns, whether the vaccination strategy has been adequate, and whether vaccination coverage is high

enough to decrease the occurrence of disease [3]. This vaccination coverage analysis showed a lower rate of vaccination than the current estimates, which suggest that 75% of the population younger than 20 years old in Brazil has been vaccinated [10]. Considering the vaccination coverage of subjects in this study and the anti-HBs detectable titers, the actual vaccination coverage in this population may vary between 57 and 70%. Nevertheless, this coverage is quite low considering that the current hepatitis B vaccination strategy should guarantee the vaccination of all individuals up to age 20. Approximately 2/3 of all individuals with proven vaccination history received the last dose of the vaccine during the first five years of life. Higher dropout rates among subjects vaccinated at older ages reinforce the importance of vaccinating children after birth, the best way of guaranteeing completion of the 3-dose schedule.

83; 95% CI 0.77–0.89; NNT 72; 95% CI 52–119), preterm delivery (RR 0.92, 95% CI 0.88–0.97; NNT 72, 95% CI 52–119), SGA infants (RR 0.90, 95% CI 0.83 to 0.98; NNT 114, 95% CI 64–625) and perinatal death (RR 0.86, 95% CI 0.76–0.98; NNT 243; 95% CI 131–1666) without increasing bleeding risk [249]. Aspirin neither increases nor decreases miscarriage risk [250] and [251]. There is no evidence of teratogenicity [252] or other short- or long-term adverse peadiatric effects. Who should receive aspirin, in what Antidiabetic Compound Library datasheet dose, and when, are unclear. Aspirin is more effective in decreasing preeclampsia: (i) among high risk women

(NNT 19, 95% CI 13–34), (ii) when initiated before 16 weeks [252], [253], [254] and [255], (iii) at doses >80 mg/day [249], [256], [257], [258] and [259]; and (iv) when taken at bedtime [260] and [261]. Adjusting

dosage based on platelet function testing may improve aspirin effectiveness [262]. Aspirin may be continued until delivery [263] (see Anaesthesia and Fluid Administration). Oral calcium supplementation (of at least 1 g/d) decreases rates of preeclampsia (RR 0.22; 95% CI 0.12–0.42), gestational hypertension (RR 0.47, 95% CI 0.22–0.97) and preterm delivery (RR 0.45; 95% CI 0.24–0.83) [218]. http://www.selleckchem.com/products/iwr-1-endo.html Three trials were conducted in low calcium intake populations but no trial included women with prior preeclampsia or reported on HELLP. No trials were identified of dietary salt restriction on preeclampsia incidence. Women with pre-existing hypertension following a DASH (Dietary Approaches to Stop Hypertension) diet may continue it. Heart healthy diets are untested. Dietary counselling to curb the rate of weight gain of overweight pregnant women has no impact on gestational hypertension or preeclampsia [224]. Pre-pregnancy or early pregnancy weight reduction is untested [225]. Periconceptual (to prevent neural tube defects and possibly, other anomalies) and ongoing regular use of multivitamins is associated with higher birthweights [264]. The Canadian FACT Trial for preeclampsia prevention is recruiting (http://clinicaltrials.gov/show/NCT01355159). Prophylactic

doses of any heparin (vs. no treatment), decreases perinatal mortality (2.9% vs. 8.6%; RR 0.40, 95% CI 0.20–0.78), delivery <34 weeks (8.9% vs. 19.4%; RR 0.46, 95% CI 0.29–0.73), and SGA infants (7.6% vs. 19.0%; RR 0.41, not 95% CI 0.27–0.61) in women at high risk of placentally mediated complications [265]. LMWH alone (vs. no treatment) reduces the risk of: ‘severe’ or early-onset preeclampsia (1.7% vs. 13.4%; RR 0.16, 95% CI 0.07–0.36), preterm delivery (32.1% vs. 47.7%; RR 0.77, 95% CI 0.62–0.96), and SGA infants (10.1% vs. 29.4%; RR 0.42, 95% CI 0.29–0.59), without a significant effect on perinatal mortality (pregnancy loss >20 weeks 1.9% vs. 5.3%; RR 0.41, 95% CI 0.17–1.02) [266]. Observed decreases in preeclampsia and a composite of placentally-mediated pregnancy complications (i.e., preeclampsia, placental abruption, SGA infants, or fetal loss >12 weeks) (18.7% vs. 42.

tb infected macrophages, and IL-2 which promotes stimulation of TH1 cells and CD8 T cells. We also showed that BCG vaccination induced IL-1α and IL-6 following BCG vaccination. There is little known about the role of IL-1α in immunity to TB; a TB case–control study in the Gambia suggested it may play a role in

TB susceptibility [12]. In TB patients from Pakistan IL-6 was shown to be increased in Culture Filtrate Protein stimulated supernatants compared to controls [13], and in South African TB patients IL-6 was increased in plasma compared to healthy endemic controls [14]. IL-6 has been regarded as a pro-inflammatory cytokine, however it has been shown to display anti-inflammatory properties which can inhibit TNFα production in CD8 T cell supernatants stimulated with mycobacterial fractions [15]. We were interested in whether Dolutegravir chemical structure those infants with greater IFNγ responses also made greater pro-inflammatory cytokine responses and smaller Rucaparib in vitro TH2 cytokine responses. We found that IFNγ responses correlated positively with production of 9 cytokines including the other pro-inflammatory cytokines measured, but also with that of the TH2 cytokines IL-5 and IL-13 and with the chemokine IL-8 and growth factor GM-CSF. The greatest fold difference between vaccinated and unvaccinated cytokine responses was seen for IFNγ. This, along with the strong evidence for correlations with many different types of cytokine, highlights the importance of IFNγ in immunity

for TB induced by BCG vaccination. Interestingly, IL-17 (a pro-inflammatory cytokine produced by the recently described TH17 T cell subset [16]) was induced unless by BCG vaccination, but there was no evidence that it correlated with the IFNγ response. This may imply that,

if there is TH17 mediated immunity induced by BCG vaccination, it is independent of the IFNγ mediated immunity and may be produced by different cells than those which produce IFNγ. IL-17 has been shown to play a role in autoimmune disease [17], [18] and [19], but has also recently been thought to play a role in M.tb infection [20], as it was shown to upregulate chemokines which led to increased recruitment of TH1 cells [21], and is also thought to recruit neutrophils to facilitate granuloma formation [22]. There is evidence that TB patients produce less IL-17 following overnight culture with ESAT6/CFP10 than contacts [23]. IL-17 has also been shown to regulate IFNγ production in cell cultures stimulated with M.tb in TB patients [24], and the IL-17 producing CD4+ T cells had characteristics of long lived central memory cells but many do not produce IFNγ [25]. The role of TH2 cytokines such as IL-4, IL-5 and IL-13 in the immune response to Mycobacterium tuberculosis has been debated, and it has been suggested that TH2 responses reflect inappropriate or suboptimal immune responses to mycobacteria [26]. Several human studies have shown that IL-4 production is increased in tuberculosis patients compared with controls [27], [28], [29] and [30].

Cell layers were rinsed twice with PBS before being fixed with 3.7% w/v paraformaldehyde for 15 min. Fixed cell layers were permeabilised using 0.1% v/v Triton X-100 in PBS for 5 min and rinsed in PBS. Samples were blocked for 30 min with 1% w/v bovine serum albumin (BSA) in PBS to prevent non-specific

binding, followed by incubation with the primary mouse anti-human MDR1 antibodies: 15 μg/ml MRK16 (Abnova, Newmarket, UK) or 20 μg/ml UIC2 (Enzo Life Entinostat chemical structure Sciences, Exeter, UK) in blocking solution for 60 min at 37 °C. Cells were washed in 1% w/v BSA in PBS to remove unbound primary antibody before incubation with a solution of the secondary FITC-labelled goat anti-mouse IgG (1:64) in PBS, for a further 30 min. Cell nuclei were counter-stained with propidium iodide (PI) 1 μg/ml in PBS for 30 s. Inserts were

washed with PBS before the filter was excised and mounted on a slide using DABCO anti-fade mounting media. Samples were imaged by a Meta 510 confocal microscope (Zeiss, Welwyn Garden City, UK), excited at 485 nm and 543 nm wavelengths and emission observed at 519 nm and 617 nm for FITC and PI, respectively. Z-stack reconstructions of samples were the average of four images for every 0.5 μm slice through the sample. On the day of 3H-digoxin transport studies, cells were detached from Transwell® inserts using trypsin and resuspended in 0.5% v/v FBS in PBS. The cell suspension was adjusted to 1 Cabozantinib price million cells/ml and 100 μl

samples were transferred to clean flow cytometry tubes. Primary anti-MDR1 antibodies (either MRK16 (1 μg) or UIC2 (0.2 μg)) were added and samples incubated at 37 °C for 30 min. Cells were washed and pelleted in cold ‘stop solution’ (0.5% v/v FBS and 0.1% w/v sodium azide in PBS). The supernatant was decanted, and cells were resuspended in 100 μl ‘stop solution’ containing FITC-labelled goat anti-mouse IgG (1:1000) and incubated at 4 °C for 30 min. After two PBS wash steps to remove any unbound secondary antibody, samples were fixed by the addition of 500 μl fixing solution (0.5% v/v formaldehyde in PBS) and stored at 4 °C in the dark for up to 1 week before analysis. An unstained Dipeptidyl peptidase sample and the appropriate isotype controls were included in each analysis to address autofluorescence and non-specific binding, respectively. For data analysis, each sample population was gated to only include cells of interest based on either their forward scatter (cell size) and/or side scatter (cell granularity) profiles. Dead cells were identified from optimisation experiments with PI and excluded from the analysis. A total of 30,000 events were collected for each sample. Raw data were analysed using WinMDI 2.9 software (build #2, 6-19-2000; Scripps Research Institute: http://facs.scripps.edu/software.html) and the mean fluorescence intensity (MFI) value was determined as MFI = [MFI value for sample] − [MFI value for isotype/unstained sample] for each marker.

The results demonstrated the existence of a linear relationship between drug concentration in plasma and anti-neuropathic pain response. selleck So, it could be possible that the plasma levels of Lamotrigine are good indicators of the concentration of the drug at its site of action. All authors have none to declare. The authors would like to thank Prof. Yogeeswari, Head, Department of Pharmacy, BITS-Hyderabad for her assistance during pharmacokinetic and pharmacodynamic studies. Authors would also like to thank The Principal, Prof (Dr). G.

Devala Rao, Director for PG Studies and Research, Dr. Buchi N. Nalluri, The convenor, Dr. C. Nageswara Rao, The secretary, Sri. P. Laxmana Rao and The President, Sri. N. Venkateswarlu of KVSR Siddhartha College of Pharamceutical Sciences, Vijayawada for their support in providing facilities during this research work. Authors are also thankful to JPR Solutions for their partial financial support for publishing this research work. “
“The structural diversity and biological importance of nitrogen containing heterocycles have made them attractive targets for synthesis over many years. Indole derivatives are biologically important chemicals with

a wide range of therapeutic properties antifungal,1 antiviral,2 Rucaparib antimalarial,3 have been reported to be associated with the indolic nucleus. Several pyrazoline, pyrrolidine and pyrazole derivatives were potent dual 5-LOX and COX inhibitors.4 Even though many biological studies have been carried out on substituted indole analogues, the antioxidant and anti-inflammatory activities on them bearing pyrazole ring were not explored. Prompted by all these observations and also in continuation of our laboratory work5, 6, 7 and 8 on reaction of indole derivatives, a simple strategy has been planned to synthesize several indole derivatives possessing pyrazoline moiety in their structure with the hope getting compounds with more potent antioxidant Resminostat and anti-inflammatory agents. In the present investigation, the synthesis of the title compounds was achieved from the simple synthetic route (Scheme 1). The yields of the synthesized compounds (7a–n) are presented in Table 1. The intermediates involved for

the synthesis of target compounds (7a–n) were 1H-indole-2-carbohydrazide (6) and substituted chalcones (3a–n). Initially, 1H-indole-2-carbohydrazide (6) was prepared by esterification of 1H-indole-2-carboxylic acid (4) afforded ethyl indole-2-carboxylate ester (5) which upon addition of hydrazine hydrate to compound (5) afforded the compound (6). On the other side, various substituted chalcones (3a–n) were prepared by the Claisen–Schmidt condensation of acetophenones and substituted aldehydes (2a–g). 9 Finally, both the intermediates (6) and (3a–n) were reacted by refluxing in the presence of catalytic amounts of glacial acetic acid to obtain target compounds (7a–n) ( Scheme 1). To the mixture of 1H-indole-2-carboxylic acid (1 mM) in DCM and ethanol is added with the addition of Conc.

In parallel, the

highly pathogenic avian influenza outbreak that threatened many countries in Asia in 2003 was a powerful argument for Brazil to increase its influenza pandemic preparedness. At that time, it was anticipated that countries without seasonal influenza production capacity, or existing contracts for the supply of vaccine, may have to wait over a year before sufficient pandemic vaccine became available to immunize their population [1] and [2]. To address these issues, Brazil sought a technology transfer partnership to construct a dedicated influenza vaccine production plant and, in the interim, to formulate and finish monovalent bulk vaccine supplied by an international vaccine producer, who would agree to become the technology provider. The objectives were to produce 25 million Cytoskeletal Signaling inhibitor doses of seasonal vaccine per year and to create a stockpile of H5N1 vaccine for use at the onset of a potential influenza pandemic. This BIBW2992 order paper describes progress towards these goals and discusses Butantan’s experience of the transfer of a complete production process. As the production of inactivated influenza

vaccine in embryonated eggs is a very standardized process, there is no regulatory uncertainty for manufacturers embarking on such production through technology transfer, provided that the vaccine seeds (also called vaccine viruses) are generated and tested under the aegis of WHO, and that the plant complies with Good Manufacturing Practice (GMP). Moreover, the basic technology to grow viruses in fertilized hen eggs is well known to virology laboratories and producers of

veterinary and human vaccines, and production technology does not vary with the influenza serotype. For Butantan, a technology supplier would also need to take account of the financial constraints of a not-for-profit organization. For example, the Institute would only be able to pay for the bulk vaccine upon transfer of funds from the Ministry of Health and approval of the vaccine Sitaxentan by the National Control Laboratory, i.e. months after receipt of this bulk in Brazil. Exchange rate fluctuations add to this concern. Butantan selected sanofi pasteur (previously Sanofi Aventis) as its bulk vaccine provider and technology transfer partner for egg-based inactivated split seasonal influenza vaccine and whole virion adjuvanted H5N1 vaccine. Two reasons guided this choice: first, sanofi pasteur’s extensive experience in large-scale influenza vaccine production, and second, the long-standing relationship of this company with Brazil. Indeed, in 1975 it was the only company to accept the challenge to build temporary facilities for the supply of meningococcal serogroup A/C vaccines to control a widespread epidemic in major Brazilian cities.