3A; 16 0 ± 2 1% versus 10 4 ± 0 1%, P < 0 05) In order to study

3A; 16.0 ± 2.1% versus 10.4 ± 0.1%, P < 0.05). In order to study the specificity of CD8+ cytotoxic T cells, spleen cells from vaccinated and control mice were co-cultured with murine fibroblasts that were co-transfected with pcDNA3.1-IL-15 and pcDNA3.1-GFP. The number of surviving IL-15 expressing target cells was determined by counting GFP positive cells. The number of IL-15 expressing target cells was reduced by 50% after incubation with spleen cells from IL-15 vaccinated mice, whereas spleen cells from control vaccinated mice, did not significantly lyse IL-15 expressing cells ( Fig. 3B; 49 ± 1% in vaccinated group versus GSK1349572 81 ± 4% in control

group, P < 0.01). Atherosclerosis was determined in control and IL-15 vaccinated mice 6 weeks after collar placement. IL-15 vaccination did not affect plasma cholesterol levels during the experiment (Fig. 3C). Quantification of Hematoxylin–Eosin (HE) stained atherosclerotic plaques showed that vaccination AUY-922 mouse against IL-15 resulted in a 75% decrease in lesion size as compared to the control group (Fig. 4A–C; 13722 ± 3116 μm2 versus 53977 ± 15332 μm2, P < 0.05). Immunohistochemical

staining for macrophages showed a significant change in plaque composition ( Fig. 4F). The relative number of macrophages per plaque area was 2-fold higher in IL-15 vaccinated mice ( Fig. 4E) than that in control vaccinated mice ( Fig. 4D), indicative for a less advanced state of the lesions in the vaccinated mice. As hypercholesterolemia

induced surface expression of IL-15 on PBMCs and spleen cells (Fig. 1B) we evaluated the effect of IL-15 vaccination on the percentage of IL-15 positive cells within the spleen and PBMCs. Spleen cells and PBMCs were stained for IL-15 and for the macrophage marker F4/80 and analyzed by FACS. Upon IL-15 vaccination, the surface expression 3-mercaptopyruvate sulfurtransferase of IL-15 on spleen cells was almost completely reduced to a level comparable to that determined in mice before the start of the Western-type diet (Fig. 5A, P < 0.05). Within the PBMC population IL-15 surface expression was also decreased ( Fig. 5A, P < 0.05). Within the macrophage population we observed an almost 70% reduction in the percentage of IL-15 positive macrophages ( Fig. 5B, P < 0.01), while the CD4/CD8 ratio in blood, indicative of the inflammatoruy status of the mice, was 3-fold lower in the IL-15 vaccinated mice ( Fig. 5, P < 0.01). Atherosclerosis is considered a dyslipidemia-induced chronic inflammatory disease of the arterial wall. During atherosclerotic lesion formation, monocytes and subsequently T cells infiltrate the arterial wall [1]. DNA vaccination against IL-15 leads in LDLr−/− mice to a blocked atherosclerotic lesion development, indicating that IL-15 accelerates lesion formation. Upon the start of a hypercholesterolemic diet in LDLr−/− mice the mRNA expression of IL-15 is increased within the spleen.

The prospect of qualifying the standard membrane feeding assay (S

The prospect of qualifying the standard membrane feeding assay (SMFA) had been questioned due to a lack of reproducibility. The SMFA had demonstrated a low sensitivity in addition to the questions about its utility in the middle ranges of transmission-blocking activity [15]. Since 2010, significant progress has been made and the SMFA assay has been qualified for the characteristics of precision, linearity, range, and specificity. The range of the assay was limited

to results of 80% or greater reduction in oocyst density, though modifications could potentially expand this range [27]. Future efforts continue toward full qualification of the assay, which, along I-BET-762 purchase with conclusive evidence that it predicts outcomes from more biologically relevant assays (e.g., direct membrane feeding assay [DMFA] and direct feeding assay [DFA]), will inform the role of the assay in the development of an SSM-VIMT. In 2012, MVI facilitated an experiment to assess the reproducibility of the SMFA across laboratories in response to the identified gaps. Using a blinded, SCH727965 standardized antibody panel encompassing a range of predetermined inhibitory activities, a number of laboratories performed independent runs of the SMFA using

their own standard operating procedures, and the raw data from each were analyzed by one group. Preliminary results were encouraging, and further work is now being pursued to determine whether the comparison of vaccine candidates being developed and evaluated by independent groups will be possible. To address the identified knowledge gap with respect to the correlation between the SMFA and transmission reduction Linifanib (ABT-869) in the field, MVI coordinated a review to compare results from the DMFA and DFA [28] in terms of efficiency of parasite infection and to better understand variability within the DMFA. In summary, the group found that the DFA is a more efficient means of infecting mosquitoes than the DMFA, though the mosquito infection rates in the DFA strongly correlated with those in the DMFA. Their work also highlighted some differences

in the feeding assay methodology, which might have contributed to assay variability and identified some gaps in our knowledge of the performance of the assays. As our understanding of the utility of each feeding assay in the different stages of vaccine development matures, the interpretation of assay readouts is also evolving (see Box 1). To progress toward the Roadmap strategic goal of a vaccine that reduces transmission, MVI released a Call for Proposals to improve the existing assays and to address the gaps in the knowledge of how the assays relate to each other. The following priority areas were targeted: quantification of variability in feeding assays; assay improvements or surrogates; and factors intrinsic to the parasite, mosquito vector, or human host that influence transmission.

Doubly distilled water was used to prepare all solutions Freshly

Doubly distilled water was used to prepare all solutions. Freshly prepared solutions were used for method development and validation. Standard tolterodine tartarate was obtained from Sigma Aldrich and tablets containing 4 mg TL were purchased from a retail pharmacy. Vismodegib manufacturer A Shimadzu UV mini-1240 UV-visible spectrophotometer with 1 cm quartz cells was used for all spectral measurements with Shimadzu UV Probe system software (version 2.1) and SCINCO, Neosys-2000 DRS-UV provided with liquid sample handling accessories. pH measurements were carried out using a calibrated digital pH meter (Neomet pH-200 L, South Korea). Phosphate buffer of pH4 was prepared by regular procedure. Require quantity of MO reagent for different concentration (0.01,

0.03, 0.05, 0.05, 0.07, 0.09 wt%) was taken in a100 mL volumetric flask then add 10 mL of 95% alcohol then the remaining volume using water. A stock solution of 1 mg mL−1 was prepared by dissolving a accurate quantity of TL in 10 mL alcohol (99%) and further diluted with water. Working standards were prepared by suitably diluting the above standard stock solution. From the 100 μg mL−1 working standard solution, various quantities were transferred in to a series of 100 mL separating funnels then add 2 mL of buffer (pH 4) and 1 mL of 0.1% w/v MO shaken well for 5 min for to complete Ponatinib clinical trial the complexation. Then 10 mL

of chloroform was added. The contents were shaken well and kept aside for few minutes. The organic layer was separated and passed through anhydrous sodium sulphate (previously dried) to remove the water in the organic layer. Full scan absorption spectrum of the yellow TL–MO ion-pair complex thus formed was obtained by scanning the chromogen extracted from 400 to 600 nm using a colorless blank solution prepared in the same way to that of sample solution. For the routine use of the method, TCL optimization was carried out for rapid and quantitative formation of colored ion-pair complexes by a number of preliminary experiments. USP23 and ICH24 guidelines were followed for method validation. The limit of detection (LOD) is the lowest possible quantity of drug can detectable by the method, and limit

of quantitation (LOQ) is the lowest possible quantity of the drug can possible to estimate by the method. LOD and LOQ were established using following formula: LOD or LOQ = κσa/b, where κ = 3 for LOD and for 10 LOQ, σ is the standard deviation with intercept (a) and slope (b). Intra-day precision was calculated from results obtained after a fivefold replicate analysis of sample on the same day. Inter-day precision was calculated from the results obtained from the same sample which was analyzed on five consecutive days. In general recovery studies were used to achieve accuracy; this was done by adding a definite amount of pure drug to a pre-analyzed sample and analyzes the mixed sample by the proposed procedure. Twenty tablets were weighed and average weight of each tablet was calculated and then grounded to fine powder.

1 mV, Fig  8) Our analysis of MK801-induced inhibition of Kv-chan

1 mV, Fig. 8) Our analysis of MK801-induced inhibition of Kv-channel currents suggests that the drug is unlikely to interact

preferentially with open or inactivated states of the Kv channels because of the following reasons. First, the inhibition was voltage-independent (Fig. 3). Many open-channel blockers inhibit voltage-gated channels in voltage-dependent manner, especially in the activation voltage range of the channels (47) and (48), because the drug-channel interaction requires channel opening and the drug-binding site is located in the Anti-cancer Compound Library transmembrane pore region. Second, the steady-state activation and inactivation of Kv channels were unaffected by MK801 treatment (Fig. 5). Although alterations in the steady-state activation and inactivation curves are not strictly required in state-dependent drug-channel interaction, most state-dependent channel blockers alter the steady-state channel kinetics (such as a left-shift of inactivation) (49) and (50). Third, when spontaneous channel activation and inactivation were prevented by holding Em at a hyperpolarized potential (−110 mV), the first depolarizing pulse after the ∼2-min treatment with MK801 produced an identical INCB018424 in vitro degree and pattern of Kv-channel inhibition as in the steady-state experiments (Fig. 4). This verifies

the hypothesis that MK801 binds Kv channels in their resting closed states and inhibits them (tonic inhibition). Fourth, the use-dependency observed in this study was minimal (Fig. 3). Although use-dependent inhibition is typically strong evidence of state-dependent inhibition, the minimal use-dependency detected here does not support the state-dependent block theory. The slow inactivation time course was markedly accelerated in the presence

of MK801 (Fig. 2). However, this does not appear to contribute out substantially to MK801 inhibition of Kv channels because of the following observation: the blockade reached maximal levels within 50 ms after application of the voltage step depolarization, when slow inactivation is apparently absent (Fig. 2 and Fig. 3A), which indicates that MK801 diminished the “peak” amplitude of the Kv-channel currents at the beginning of the depolarizing pulse. Based on these results, we suggest that MK801 inhibits Kv channels primarily by binding to the channels in their closed states and reducing channel availability or decreasing channel conductance. The blockade of Kv channels by MK801 in RMASMCs reported here is highly similar to the inhibition of the channels by ketamine (14). The ketamine block of Kv channels was also voltage-independent and did not alter steady-state channel kinetics. However, MK801 inhibits Kv channels in RMASMCs more potently (IC50 of ∼100 μM) than ketamine (IC50 of ∼500 μM).

VP7(T13) is an immuno-dominant orbivirus-species/serogroup-specif

VP7(T13) is an immuno-dominant orbivirus-species/serogroup-specific antigen [51], [60] and [61]. Antibodies to VP7 can neutralise the infectivity of BTV core-particles, but do not significantly neutralise intact virus particles [62]. The incorporation of baculovirus-expressed VP7 in previously reported vaccination studies using VP2 and VP5, also failed to enhance NAb

responses in sheep [43]. However, vaccination with BTV-VP7 has been shown to induce a partially-protective www.selleckchem.com/products/AC-220.html cytotoxic T-cell response that may reduce viraemia [63]. Capripoxvirus expressing VP7 was shown to confer cross-protection [51]. Although vaccination with baculovirus-expressed BTV core-like-particles (CLP – containing VP3 and VP7) did not prevent clinical signs of the disease, it did reduce their severity [44]. The addition of expressed VP7 to vaccination antigens (with VP5Δ1–100 and soluble domains of VP2) failed to increase neutralising antibody titres (against BTV-4) and failed to protect IFNAR−/− mice from lethal challenge with BTV-8. Regardless of the antigen combination which we Ibrutinib price used, there was no protection from the heterologous BTV-8 lethal challenge. These results show that the response to immunisations is serotype-specific and that VP2 is the main protective component in the three combinations of antigens. The results presented show that soluble BTV-VP2 domains and VP5 can be expressed in

bacteria, suggesting that they adopt a native conformation/fold in this system. The aim of this study was to assess bacterially-derived BTV structural-proteins as candidates for a DIVA-compatible subunit-vaccination-strategy, using Balb/c mice and the well-established BTV animal-model, IFNAR−/− mice. DIVA-compatible BTV vaccines could be based on a subset of the viral proteins, with detection of antibodies to the remaining protein(s) as surveillance markers for previous infections. Our results demonstrate potential for a bacterial-expressed BTV-subunit DIVA vaccine, based principally

on VP2 and VP5. The exclusion of VP7, which does not seem to influence protection, provides a mean for DIVA. The two expressed VP2 domains, VP2D1 and VP2D2 others combined on equimolar basis, generated high titres of neutralising antibodies with similar titres in both Balb/c and IFNAR−/−. Although a transient viraemia was observed in mice immunised with VP2D1 + VP2D2, post-challenge with BTV-4, this was rapidly cleared and they survived without signs of infection throughout the experiment. This indicates that soluble bacterial-expressed antigens are protective and do not require more complex eukaryotic expression systems. The use of bacterial-expressed protein antigens, could provide a safe and scalable alternative to live-attenuated BTV vaccines. Bacterial expression could represent an alternative to inactivated vaccines, particularly if viruses prove to be difficult to propagate in cell culture (like BTV-25 [7]).

Briefly, OMVs from serogroup B meningococci were adsorbed to fluo

Briefly, OMVs from serogroup B meningococci were adsorbed to fluorescent polystyrene latex microspheres (Fluoresbrite Plain Microspheres, Polysciences, Warrington, Pennsylvania) of approximately size of meningococci (1 μm of diameter). FITC was incorporated within the polymer, leaving the surface free to adsorb

the protein. The latex beads (500 μl, 4.55 × 1010 beads/ml) buy BMS-354825 were centrifuged at 15,600 × g for 5 min, and the pellet was suspended in a 940 μg/ml solution of OMV in 0.1 M borate buffer (0.1 M boric acid, adjusted to pH 8.5) followed by end-to-end rotation overnight (20 h) at 20 °C. After additional blocking of unreacted sites on the OMV beads with 2% bovine serum albumin (BSA) in 0.1 M borate buffer, the OMV-bead pellet was suspended in storage buffer (0.1 M phosphate buffer, containing 5% glycerol, 0.02% merthiolate and 1% BSA, pH 7.4), and kept protected from daylight in aliquots

at 4 °C until used. The antigen coated bead suspensions (100 μl, 3.3 × 108 beads/ml) were opsonised for 8 min with 25 μl of diluted test serum (1:20) previously heat inactivated at 56 °C for 30 min, with a total sample volume of 400 μl obtained by addition of PBS–BSA, supplemented with CaCl2 (0.98 mM) and MgCl2 (1 mM). 25 μl of human serum that lacked detectable intrinsic opsonisation activity diluted at 1% was added to the reaction and were incubated with end-to-end rotation for 8 min at 37 °C. Donor leukocytes (100 μl, 1.25 × 107/ml) were added and the suspensions Etomidate were incubated for 8 min. Phagocytosis was terminated by adding 1.5 ml of ice-cold PBS supplemented with 0.02% EDTA. The suspensions were kept on ice until analyzed Carfilzomib mw by a FACScalibur flow cytometer [16]. The levels of significance of the differences between groups were examined by Paired or Unpaired t test (parametric tests) For nonparametric data we used Mann–Whitney test (unpaired samples) or Wilcoxon matched pair test (paired samples). These analyses were performed with a GraphPad-Prism software, version 4.02. P < 0.05 was taken as significant. Fig. 1A shows the percent of specific

memory B-cells detected as specific ASC after in vitro stimulation of peripheral blood memory B-cells for 6 days. Memory B-cells were detected only in one individual 7 days after the first dose (0.5%) and in 2 individuals at 14 days (mean of 0.16%). A significant memory B-cell response was seen 7 days (mean of 0.27%) and 14 days (mean of 0.46%) after the third vaccination. At this time, memory B-cells were detected in all individuals, with frequencies varying from 0.14 to 0.95%. A significant decrease of memory B-cells was recorded 6 months (mean of 0.03%) later (pre-booster). Surprisingly, 14 days after the booster dose, only 2 of 5 individuals responded with an increase in memory B-cell frequencies with values of 0.15% and 0.34% (mean of 0.1% for all individuals). As can be seen in Fig. 1B, we observed a continuous and gradual decrease (P > 0.

Here again, the target antigens have been recently precised (resp

Here again, the target antigens have been recently precised (respectively TIF1-γ and MDA5) [13], ELISA have been developed, leading to think that routine test will soon be available. All these efforts for the development of immunological or pathological tools and finally for a better classification of the myositides are aimed to define homogeneous groups of patients, receiving appropriate treatments. It is now accepted that conventional immunosuppressants (corticosteroids, methotrexate, azathioprine, intravenous immunoglobulins…) have no (or transient and

modest) effects on muscle strength during IBM. It is then extremely important to distinguish this condition from PM, to avoid useless (and potentially dangerous) treatments. Nevertheless, selleck the debate is still open SRT1720 concerning the primum movens of IBM: is it an immunological [5] or a degenerative [4] phenomenon? The development of future therapeutic strategies (and trials) will thus depend of the investigator’s convictions: unconventional immunosuppressant

and/or modulator (such as certain biotherapies) in one hand or anti-amyloid (such as in Alzheimer disease) on the other. Nonetheless, for the other more easily treatable myositides, one may be surprised, in 2011, by the weakness of evidence-based medicine [14] and the lack of recommendations. It is also surprising that in most of the studies, PM, DM, overlap syndrome with muscle inflammation or IMNM are indistinguishably treated in the same manner [14], despite their different physiopathogenesis. This is presumably due to the rarity of these diseases, and the lack of worldwide, concerted effort

to date. However, things are undisputedly changing, as preclinical models are now mature [3], that will help for the choice of the molecules to be tested. Efforts are made to set up and standardize diagnostic criteria and to define outcomes for the future clinical trials, not only in PM/DM/IMNM [7] but also in IBM [15] and [16] and other international workshops are planned. Furthermore, big pharmaceutical companies are developing biotherapies potentially targeted for myositides and their interest for these diseases PDK4 seems to progress. We can thus be quite enthusiastic: no doubt that all these efforts will allow, in the near future, to start multicentric, prospective, randomised trials for the benefit of the patients. none “
“Inflammatory or necrotizing myopathies, myositides and other acquired myopathies, new insight in 2011. O. Benveniste et al., Paris, France Observations on the classification of the inflammatory myopathies D. Hilton-Jones, Oxford, United Kingdom Pathogenic aspects of dermatomyositis, polymyositis and overlap myositis R.K.

4C) The infiltrates were mainly located in perivascular and peri

4C). The infiltrates were mainly located in perivascular and peribronchial areas (Fig. 4B). However, for mice immunized with Qβ-Eot, Qβ-IL-5 or a combination of both, lung inflammation was substantially reduced (Fig. 4D–F). It was also evident that the eosinophilic component of the lung-infiltrates of vaccinated mice was markedly reduced. Indeed, eosinophils no longer represented the major infiltrating

cell type. H&E staining supported these observations. IL-5 http://www.selleckchem.com/products/lee011.html has been shown to be important for the development of eosinophils in the bone marrow and for their release into the peripheral circulation [7], [8] and [9]. Furthermore, eotaxin together with IL-5 are important for the distribution of eosinophils into the tissues

[12]. Consequently, inhibiting the biological activity of either one of these key molecules by administration of anti-IL-5 or anti-eotaxin monoclonal buy Cabozantinib antibodies diminished eosinophilia in response to antigen inhalation in mouse models of asthma [15]. Although therapies with monoclonal antibodies are highly effective, they may have some limitations, including high costs, immunogenicity of mAbs and poor pharmacokinetics [31], [32] and [33]. In some cases, active vaccination strategies might offer a valuable alternative [34]. In a recent preclinical study, active immunization with a DNA vaccine against IL-5 was shown to bypass immunological tolerance, induce neutralizing antibodies and reduce airways inflammation and eosinophilia. However, at least four injections were needed to obtain a 100% response and long lasting effects

of this vaccine have not yet been demonstrated [35]. Furthermore, DNA vaccination has proven to be unsuccessful at inducing antibody responses in humans. In contrast, a number of studies in mice [21], [22], [23], [24], [25] and [36] and humans [37], [38], [39] and [40] with VLP-based vaccines have shown that highly repetitive display of antigens on VLPs results in potent antibody responses. Indeed, self-specific antibody responses with clinically meaningful efficacy have been achieved with such vaccines [26]. Antibodies check induced by active immunization with VLP-based vaccines decline relatively slowly over time with a estimated half-life of 2–3 months [26] and [37] and titers can be boosted or at least maintained by additional immunizations making it an attractive strategy to treat chronic disease. In this study, we have shown that a single immunization with Qβ-IL-5 or Qβ-Eot resulted in a 100% responder rate in the absence of adjuvant. Furthermore, by using a combined vaccination strategy, neutralizing antibodies against IL-5 and eotaxin could be simultaneously induced and maintained. In murine models of asthma, inhibition or lack of IL-5 consistently suppresses pulmonary eosinophilia in response to antigen inhalation; however, this effect does not always correlate with improved lung function [41].

The log antibody concentrations one month post-mPPS are significa

The log antibody concentrations one month post-mPPS are significantly associated with the pre-mPPS antibody concentration for all 16 non-PCV serotypes (each p < 0.001). Having selleck products adjusted for the pre-mPPS log antibody concentration, exposure to 23vPPS was associated with a lower response to mPPS for all 16 non-PCV serotypes (each p < 0.001). For PCV serotypes, a similar response was demonstrated.

The response one month post-mPPS was significantly associated with the pre-mPPS antibody concentration for all seven PCV serotypes (p < 0.001) and having adjusted for the pre-mPPS concentration, prior exposure to 23vPPS was associated with a lower response to mPPS (each p < 0.001). In contrast, most children who had not received 23vPPS had an increase in antibody concentration. A joint test rejected the

null hypothesis of mPPS having no impact on the antibody response to any of the 23 serotypes, having adjusted for the pre-mPPS antibody concentrations (p < 0.001). There were 101 SAE's throughout the study period with none attributable to receipt of any of the study vaccines. In children over 12 months of age, there were 14 SAE's in the 12 month 23vPPS group and 22 SAE's in the group that did not receive the 23vPPS. There were four cases of inpatient pneumonia in children who had received the 12 month 23vPPS compared to seven cases in those that had not, www.selleckchem.com/products/PF-2341066.html in infants aged over 12 months of age. There were no cases of IPD throughout the study period. This is the first study in children, using the third generation WHO ELISA assay to measure antibody responses

to all 23vPPS serotypes following receipt of that vaccine. The results show that prior receipt of 23vPPS causes immune hyporesponsiveness to a subsequent 23vPPS challenge. Despite those children who received the 12 month 23vPPS having higher circulating antibody concentrations at 17 months of age, their responses to a re-challenge with a small dose of 23vPPS demonstrated a profound lack of response to all 23 serotypes after adjusting for the pre-existing antibody concentration. In contrast, those children who had not received the 12 month 23vPPS 3-mercaptopyruvate sulfurtransferase could clearly mount a satisfactory response to mPPS. There are a number of potential immunological mechanisms that may explain these findings. In vitro studies have suggested that polysaccharides antigens may be able to down regulate B cells [30], and that newly formed antibody via IgG, IgM, or immune complexes can bind to inhibitory Fc receptors and prevent antibody production [31]. The critical role of pneumococcal-specific memory B cells in first line of defense against pneumococcal infection has recently become an important area of research.

Tools for tackling meningococci that express four of the disease-

Tools for tackling meningococci that express four of the disease-associated seogroups (A, C, Y and W) are to hand in the form of protein-conjugate polysaccharide vaccines [5]. At least in the case of the meningococcal C polysaccharide conjugate (MCC) vaccines, immunisation BMN 673 in vivo of the population in which transmission is occurring can disrupt transmission to the extent that the circulation of potentially invasive organisms can be reduced to a very low level, if not completely eradicated [36] and [37]. In a number of countries this has been achieved for serogroup C meningococci,

with little convincing evidence of the replacement of these organisms with other harmful meningococci. The goal would be to eliminate serogroup A,

B, C, W, Y, and Selleck Duvelisib perhaps X capsules: more specifically this means removing from the meningococcal population the Region A variants of the cps genome region which encode the synthesis genes for these serogroups [38]. A three-phase programme for the control or elimination of invasive meningococci can be envisaged: Phase I would target serogroup A and serogroup C meningococci at the global level. Effective conjugate vaccines exist against these organisms, including the recently introduced MenAfriVac vaccine [39], developed to be affordable in sub-Saharan countries [40]. Phases I and II are feasible with current technology, if challenging from a logistical point of view. Indeed, in one of the most exciting developments in the history of meningococcal disease control, the rollout of the MenAfriVac conjugate serogroup A polysaccharide Isotretinoin vaccine presents the prospect of the end of epidemic group A meningococcal disease in sub-Saharan Africa [35]. The goal of the Meningitis Vaccine Project (MVP) was the sustainable introduction of a serogroup A conjugate polysaccharide vaccine, with the vaccine priced a less 1US$ per dose, a goal that was achieved by a novel North–South partnership of technology

transfer and manufacturing capacity [40]. Other factors aiding the elimination of serogroup A meningococci is their relative lack of genetic diversity and geographical distribution. Virtually all cases of serogroup A disease are caused by one of three clonal complexes, ST-1 complex and the closely related ST-4 and ST-5 clonal complexes [44]. This is different from sialic acid-containing serogroups B, C, W and Y which are found in numerous genetically divergent clonal complexes. Similarly, whilst the sialic acid capsules are globally distributed, much of the serogroup A disease is in Africa and Asia [9], [44] and [45], with certain regions currently experiencing little or no serogroup A disease [16].