, 1995) N/OFQ and its receptor, NOPR, are widely expressed in th

, 1995). N/OFQ and its receptor, NOPR, are widely expressed in the brain, where they control the release of other neurotransmitters through presynaptic actions (Darland et al., 1998; Neal et al.,

1999). Despite its structural homology with opioid peptides, N/OFQ does not bind to the opioid receptors and, conversely, opioid peptides do not activate the NOPR (Reinscheid et al., 1996). Additionally, while opioid-like N/OFQ elicits pronociceptive effects after intracranial administration, giving rise to the name nociceptin (Meunier et al., 1995), and acts in the brain to produce functional antiopioid effects, it blocks opioid-induced supraspinal analgesia (Mogil et al., 1996), morphine-induced CPP (Ciccocioppo et al., 2000; Murphy et al., 1999), and this website morphine-induced increases in extracellular DA levels in the nucleus accumbens (NAC) (Di Giannuario and Akt inhibitor Pieretti, 2000). Activation of NOPR produces anxiolytic-like effects (Gavioli and Calo’, 2006; Varty et al., 2005) that appear to be particularly robust under stressful conditions, such as during alcohol withdrawal (Economidou et al., 2011). This may depend upon the ability of N/OFQ to act as a functional antagonist for extrahypothalamic actions of CRF and CRF1R activation. For instance, it has been shown that N/OFQ blocks the anorectic and the anxiogenic-like effects of CRF, with the BNST being the site of the interaction between the two systems (Ciccocioppo et al., 2003; Rodi

et al., 2008). In addition, N/OFQ opposes the ability of CRF to facilitate GABAergic transmission in the CeA, an effect that is more pronounced in slice preparations from rats undergoing alcohol withdrawal, a state known to be associated with Mephenoxalone enhanced stress reactivity and overactive CRF neurotransmission (Cruz et al., 2012). These data provide converging evidence supporting the

possibility that NOPR activation may result in particularly beneficial antistress and anxiolytic-like effects when the CRF system is activated. This view is supported by gene expression data showing that exposure to stressful conditions, such as alcohol withdrawal or intracranial CRF administration, leads to upregulated NOPR expression in the BNST, which may explain in part the enhanced efficacy of N/OFQ to produce antistress effects under these conditions (Martin-Fardon et al., 2010; Rodi et al., 2008). Several studies have demonstrated that activation of the NOPR blunts the reinforcing and motivational effects of alcohol across a range of behavioral measures, including alcohol intake (Ciccocioppo et al., 1999), CPP (Kuzmin et al., 2003), and relapse to alcohol seeking triggered by alcohol-associated cues (Ciccocioppo et al., 2004) or stress (Martin-Fardon et al., 2000). The latter result is particularly noteworthy, because relapse-like behavior triggered by stress or cues are otherwise to a large degree pharmacologically dissociable (Shalev et al., 2002).

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As a result, all currently known active zone proteins were identi

As a result, all currently known active zone proteins were identified based on antibodies, genetic mutations, or protein-protein interactions. Emerging evidence suggests that five evolutionarily conserved proteins—RIM, Munc13, RIM-BP, α-liprin, and ELKS proteins—form the core of active zones (Figure 2). RIM, Munc13, and RIM-BP are multidomain proteins composed of a string of identifiable modules, whereas α-liprin and ELKS exhibit a simpler structure. These proteins are generally encoded by single genes in invertebrates and by multiple genes, often with several splice variants, in vertebrates.

Bcl-2 cleavage The five core active zone proteins form a single large protein complex that Afatinib docks and primes synaptic vesicles, recruits Ca2+ channels to the docked and primed vesicles, tethers the vesicles and Ca2+ channels to synaptic cell-adhesion molecules, and mediates synaptic plasticity (Figure 3). Interestingly, the core active zone proteins are not specific for active zones, or even neurons. ELKS and α-liprins were discovered in nonneuronal cells (Serra-Pagès et al., 1995; Nakata et al.), and RIMs, Munc13s, and RIM-BPs are at least partially expressed in neuroendocrine and other secretory cells, suggesting that these

proteins perform additional general functions. In addition to these five core active zone proteins, piccolo and bassoon (two large homologous proteins) are associated in

vertebrates with active zones (tom Dieck et al., 1998, Wang et al., 1999, Fenster et al., 2000 and Limbach et al., 2011), and proteins related to C. elegans SYD-1 are important for the assembly of active zones in invertebrates ( Hallam et al., 2002, Patel et al., 2006 and Owald et al., 2010). Other proteins are also likely present in active zones or close to them, but the evidence for their importance is not always strong, and only some of these proteins will be discussed below (e.g., CASK and Pick1). Besides these proteins, actin was suggested to be an active zone component, but high-resolution electron microscopy (EM) shows that actin filaments are excluded from the active zone 4-Aminobutyrate aminotransferase and the vesicle cluster ( Fernández-Busnadiego et al., 2010). Furthermore, as noted above, the plasma membrane SNARE proteins syntaxin and SNAP-25 and the SM protein Munc18 that are components of the synaptic vesicle fusion machinery for exocytosis ( Südhof and Rothman, 2009) are not enriched in active zones but distributed all over the plasma membrane. This may appear paradoxical given that synaptic exocytosis is restricted to active zones but is consistent with the general involvement of these proteins in many types of exocytosis. RIMs (for Rab3-interacting molecules; Wang et al.

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, 1996) Thus far, most attention has been focused on short-term

, 1996). Thus far, most attention has been focused on short-term interactions between electrical and chemical synapses on the millisecond timescale, but it has long been speculated

that chemical synapses may also drive long-term regulation of mammalian electrical synapses see more (Connors and Long, 2004). Electrical synapses can undergo long-term modification by spiking activity (Haas et al., 2011), metabotropic neurotransmitters (Landisman and Connors, 2005 and Mills and Massey, 1995), and dopaminergic activation (Kothmann et al., 2009). While experiments in goldfish Mauthner cells have shown that activation of fast glutamatergic synapses can produce long-term potentiation of neighboring electrical synapses (Yang et al., 1990, Pereda and Faber, 1996 and Smith and Pereda, 2003), whether chemical synaptic input can also regulate the strength of mammalian selleck electrical synapses in the long term remains

unclear. The electrically coupled neurons of the inferior olive represent a particularly attractive system for attacking this question. Electrical coupling is mediated by Connexin 36 gap junctions formed between dendritic spines of neighboring olivary cells (Long et al., 2002). Importantly, the gap junctions are located in close proximity to glutamatergic and GABAergic synapses housed within a glomerular structure (Llinas these et al., 1974, Sotelo et al., 1974, de Zeeuw et al., 1989, de Zeeuw et al., 1990a and de Zeeuw et al., 1990b): an anatomical arrangement that provides an excellent substrate for intersynaptic interaction. While fast, short-term modulation of olivary electrical coupling by both GABAergic and glutamatergic synaptic

inputs has long been suggested (Llinás, 1974, De Zeeuw et al., 1998, Lang, 2002, Jacobson et al., 2008, Hoge et al., 2011 and Bazzigaluppi et al., 2012), no direct evidence exists to support long-term modulation of electrical synapses in the mammalian inferior olive. Here we have addressed this question by performing simultaneous patch-clamp recordings between coupled neighboring olivary neurons. We demonstrate robust, long-term depression of electrical coupling triggered by physiological patterns of glutamatergic synaptic input. We obtained simultaneous recordings from electrically coupled pairs of olivary neurons in the principal olive and medial accessory olives in rat brainstem slices. Electrical coupling was measured by injecting negative current pulses into either cell (Devor and Yarom, 2002 and Landisman and Connors, 2005) and assessing the resulting voltage change in the noninjected cell. Coupling was detected between almost all neighboring neurons (with a coupling probability higher than 80%). The mean coupling coefficient was 0.

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The differences

between syb2 and vti1a slope values durin

The differences

between syb2 and vti1a slope values during chemical stimulation are significant in both 2 and 8 mM extracellular Ca2+. Figures 4C and 4F depict the cumulative data as a percentage of total internal fluorescence after NH4Cl application. The inset depicts a sample graph indicating how the changes http://www.selleckchem.com/products/NVP-AUY922.html in fluorescence were calculated. The percentage of vti1a residing in internal compartments released during 90 mM K+ stimulation is significantly less than that of syb2 in both 2 and 8 mM CaCl2. The percentage of vti1a molecules that are trafficked at rest is significantly more than syb2 in the presence of 2 mM extracellular Ca2+, but the spontaneous trafficking of syb2 and vti1a is approximately equal in the presence of elevated extracellular Ca2+, corroborating earlier results (Figure 2). These results show that the majority of vti1a trafficking occurs at rest, and even with strong elevated K+ stimulation, vti1a-containing vesicles are released at a lower rate compared to those containing agonist syb2. Furthermore, the simultaneous visualization

of syb2 and vti1a trafficking during the 90 mM K+ stimulation strongly suggests that these proteins largely reside in different vesicular pools. We next assessed the simultaneous trafficking of VAMP7-pHluorin and syb2-mOrange. In experiments like those described for vti1a, syb2-mOrange was expressed in the same neurons as VAMP7-pHluorin, and their spontaneous and evoked trafficking was measured simultaneously. Syb2-mOrange trafficked robustly both at rest and with 90 mM K+ stimulation, but significantly less VAMP7 trafficking was observed under either condition (Figure S5). These results are comparable to earlier findings (Figure 2). While we did not observe robust mobilization of VAMP7-pHluorin either at rest or with stimulation, old in contrast to Hua et al. (2011), this is likely a

result of the autoinhibitory actions of the longin domain, which was present in our full-length VAMP7 construct. Still, a measurable amount of VAMP7-pHluorin trafficking was seen in the same synapses as syb2-mOrange, which agrees well with the basic finding of their report that VAMP7 is targeted to a subpool of SVs. In light of recent work showing a role of endosomal sorting in SV recycling (Hoopmann et al., 2010), we evaluated the overlap between the trafficking behaviors of vti1a and two bona fide endosomal markers, transferrin receptor (TfR) (Kennedy et al., 2010) and syntaxin-6 (Rizzoli et al., 2006) (Figure S6). TfR and syntaxin-6 showed limited spontaneous trafficking in synapses compared to vti1a. Thus, although vti1a resides in endosomes (Antonin et al., 2000a, Bethani et al., 2009 and Kunwar et al., 2011) in addition to its presence on SVs (Antonin et al., 2000b and Takamori et al.

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The antibody readily detected TMEM16B-mCherry (monomer ∼132 kDa)

The antibody readily detected TMEM16B-mCherry (monomer ∼132 kDa) expressed in HEK293 cells, but not in

control cells cotransfected with enzymatically prepared small interfering RNA (esiRNA) (Kittler et al., 2005) targeting TMEM16B (Figure S3B). Using this rabbit anti-TMEM16B antibody to probe for the endogenous TMEM16B, we detected a band migrating at the expected size of TMEM16B (∼105 kDa) in cultured mouse hippocampal neurons (Figure 4H). These studies reveal that TMEM16B is expressed in the hippocampus. To test for the involvement of TMEM16B in hippocampal CaCC, we cloned two independent small hairpin RNAs (shRNAs) targeting different parts of the TMEM16B mRNA, 16B-shRNAs #2 and #5, as well as a scrambled control shRNA into a lentiviral transfer vector that contains the coding sequence for green fluorescence protein (GFP). These TMEM16B-shRNAs reduced the expression of TMEM16B-mCherry Carfilzomib in vitro fusion proteins in HEK293 cells (Figure S3C) as well as endogenous TMEM16B mRNA in cultured hippocampal neurons 10 days after lentivirus infection ( Figure 4B). Whereas these infected neurons displayed normal Ca2+ current, shRNA #2 or shRNA #5 knockdown

of TMEM16B reduced the tail current amplitude by 60% ± 4.5% and 61% ± 5%, respectively, 12 days after infection ( Figures 4C and 4D). Significant reduction of the tail current was also observed check details at 9 and 10 days after infection ( Figure 4D). In contrast, comparison of CA1 pyramidal neurons in hippocampal slices from wild-type (n = 7) and TMEM16A KO mice (n = 11) revealed no significant difference in the tail current (109% ± 9% of control with 0 mV prepulse, p = 0.9) ( Figure S3A), indicating that TMEM16B but not TMEM16A is required for the CaCC in hippocampal pyramidal neurons. Knockdown of TMEM16B by shRNA #2 or shRNA #5, but not the scrambled control RNA, lengthened the

action potential duration by 50% ± 7.6% and 40% ± 5.2% respectively; the action potential broadening was evident starting at 9 days Phosphoprotein phosphatase after infection, as well as 10 and 12 days after infection (Figures 4E). We further tested the effect of shRNA knockdown of TMEM16B by performing whole-cell recording of CaCC elicited by raising intracellular Ca2+ in the patch pipette solution from 0 to 0.5 μM Ca2+, and found ∼80% reduction of CaCC current 10 days after lentivirus infection (Figure 4F). These studies indicate that TMEM16B is important for hippocampal CaCC that regulates the spike waveform. Blocking CaCC caused spike broadening in CA1 and CA3 pyramidal neurons recorded at 35°C (Figures 3B and 5A) and room temperature (Figure S4), and the spike broadening persisted in the presence of 100 μM calcium/calmodulin activated kinase II (CaMKII) inhibitor KN62 (Figure S4).

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Follow-up studies will be needed to determine if the


Follow-up studies will be needed to determine if the

durability of the responses to two and three doses remain comparable. However, these results have already prompted some jurisdictions to initiate programs that delay administration of the third dose for at least 5 years, with an interim assessment to determine if it is needed. The immunogenicity of Gardasil® and Cervarix® was also assessed in mid-adult women. In the Gardasil® efficacy trial, peak titers trended modestly downward with age when stratified into 16–23, 24–34 and 35–45 age groups [46]. However, seroconversion rates, measured one month after the third dose in cLIA assays, were greater than 97% for all vaccine types. At month 48, seropositive rates in 24–45 year-olds were 91.5%, 92.0%, 97.4% and 47.9% for HPV6, 11, 16, and 18, respectively. The loss of Libraries seropositivity to HPV18 in half of the mid-adult women mirrors the loss in approximately selleck chemicals one third of young women [60]. As mentioned above, this finding may be more related to the specific performance of the HPV18 cLIA used in the analysis, than lower immunogenicity of the HPV18 VLPs used in the vaccine. In a Cervarix® trial GDC-0973 molecular weight of women ages 15–55, all women

seroconverted to both HPV16 and 18 at one month after the last dose, as measured in a VLP ELISA [48]. Although peak and plateau titers were higher for the 15–25 year-old group than the 26–45 and 46–55 year-old groups, all women remained seropositive at month 24. GMTs in the 46–55 year-olds remained 16-fold (HPV16) and 8-fold (HPV18) higher than the GMTs elicited by natural infection. Thus, mid-adult GPX6 women are able to mount robust antibody responses to both vaccines. HIV-infected individuals have an increased risk of persistent HPV infection, HPV-associated benign lesions and HPV-associated cancers. It is therefore of interest to determine the immune response to the vaccines in HIV-infected individuals. Safety and immunogenicity of

Gardasil® was assessed in separate studies of adult males (ages 22–61) and children (ages 7–12) [70] and [71]. The vaccine was safe and well tolerated in both studies, with no adverse effects on CD4+ cell counts or plasma HIV RNA levels. Seroconversion rates were greater than 95% and antibody titers were approximately 50% of those measured in HIV-uninfected individuals of similar age. These findings encourage targeted vaccination programs for young HIV positive individuals. Since several other vaccines are routinely given to adolescents, it is important to determine if they can be co-administered with the HPV vaccines. Recent studies have demonstrated safety and non-inferior immune responses when Gardasil® was co-administered with Recombivax HB® (hepatitis B; Merck & Co., Whitehouse Station, NJ USA) [72], Repevax® (diphtheria, tetanus, acellular pertusis, inactive polio; Sanofi Pasteur MSD, Lyon France) [73], or Menactra® (meningococcal conjugate; Sanofi Pasteur, Inc.

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Pharmaceutical companies do not play any financial role in the CT

Pharmaceutical companies do not play any financial role in the CTV decision making process even though representatives may be invited to make specific presentations at the selleck compound discretion of the

committee. Once a year, the CTV holds a specific meeting during which industry representatives are formally invited to present their activities; this allows the CTV to remain up-to-date about advances in the private sector. Special interest or lobbying groups do not provide any funding or other resources, nor do they intervene in the decision making process. Two contrasting examples of decision making by the committee illustrate the gap between the committee’s recommendations and the ultimate decisions that were put into place. The first example inhibitors concerns HPV vaccination.

The Ministry of Health and the media exerted pressure on the CTV by publicly announcing that there would be reimbursement of the HPV vaccine before the CTV issued its opinion. The difficulty in assessing the vaccine’s cost-benefit status and target populations prompted the CTV to seek an economic evaluation and to decline on issuing its full recommendations by Anti-cancer Compound Library cell line the requested date (rather, it issued limited recommendations concerning screening by cervical smear). Its final opinion was issued a few months later. However, media coverage of the HPV vaccine was very strong, and some people even considered it excessive. This subsequently led to vaccinations being overwhelmingly administered

to the “catch-up” bracket group (women aged 15–23 years), with very little allocated to cover vaccinations for the targeted cohort group (girls under 14 years of age). The other example concerns the meningococcus C vaccine, in which this case, there was no external pressure exerted on the CTV. The CTV reconsidered previous recommendations that were made on vaccination campaigns conducted in hyper-endemic areas. The epidemiological findings from the areas covered by the however vaccination campaigns, which were compared with national data, played an important role in the decision making process. An economic evaluation resulted in the development of a vaccination strategy that is based on a single-dose immunization of one-year-old children, accompanied by a large “catch-up” effort for children, adolescents, and young adults. This was recommended in order to promote herd immunity, which can protect infants not targeted by vaccination. In France, more than 80% of the vaccines are administered by mainly general practitioners (GPs), as well as private practitioners and pediatricians. Thus, a major issue lies in how to disseminate the recommendations and have them understood and accepted by physicians. The CTV uses various tools for sharing information on CTV activities with the medical profession and the public.

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The results of this trial are consistent with the results of two

The results of this trial are consistent with the results of two other trials that evaluated the use of Kinesio Taping in people with chronic low back pain. One

study16 allocated people into three groups (Kinesio Taping and exercises, Kinesio Taping only and exercises only). The outcomes assessed in this study were pain intensity, disability and lumbar muscle activation measured by electromyography. No between-group differences were observed. Another study17 compared the effect of Kinesio Taping versus the control procedure of the present trial (Kinesio Taping without convolutions) for the outcomes pain, disability and range of motion for trunk flexion. People Modulators received only one application of the tape, which remained in situ for Nutlin-3a cell line one week. This study also did not identify any differences in favour of the Kinesio Taping. We do not know of any studies that have evaluated the Kinesio Taping Method using the global perceived effect scale. There are five published systematic reviews15, 28, 29, 30 and 31 evaluating the effectiveness of Kinesio Taping; one

specifically targeted the treatment and prevention of sports injuries,15 two examined different clinical conditions,29 and 30 and two looked at musculoskeletal conditions.28 and 31 However, none of these reviews found any clinically worthwhile benefits for this intervention. The studies compared Kinesio Taping with a range of treatments, as well as with no treatment selleck inhibitor and placebo. These studies were, on average, of moderate methodological quality, with small sample sizes and very small follow-up periods. Regardless of the comparisons used (as well as the outcomes investigated), the results of clinical trials conducted so far have shown no difference or found just a trivial effect in favour of Kinesio Taping. Our group conducted the most updated systematic review32 with the greatest number of

clinical trials relevant to musculoskeletal conditions and our conclusions were similar to the existing reviews. The results of the present study challenge the importance of the presence of convolutions in Kinesio Taping for effectiveness of treatment in people with chronic low back pain. According to the creators of the Kinesio Taping Method14 these from convolutions increase blood and lymphatic flow, and aid in reducing pain. Therefore, applying proper tension is one of the key factors for effective treatment.14 However, the outcome with convolutions was not superior to the control group and so the improvement seen in both groups cannot be due to tape tension. The results of the present study challenge the theory that these convolutions are part of the mechanism. To date, the present study is the largest clinical trial conducted on the effectiveness of Kinesio Taping.

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Amongst them, IL-5 is responsible

for the selective diffe

Amongst them, IL-5 is responsible

for the selective differentiation of eosinophils [7]. IL-5 also stimulates release of eosinophils from the bone marrow into the peripheral circulation and promotes their migration to the lung upon allergen challenge; a key step in the development of lung inflammation [8] and [9]. In accord with these important roles for IL-5, antibodies that www.selleckchem.com/products/DAPT-GSI-IX.html neutralize IL-5 inhibit both allergen-induced blood eosinophilia and the recruitment of eosinophils to the lung in murine models of asthma [10] and [11]. In addition to IL-5, cytokines from the eotaxin family also stimulate eosinophils to migrate from blood into tissues [12]. There are two variants of murine eotaxin, namely eotaxin 1 (eotaxin) and eotaxin 2 which both belong to the family of CC type chemokines [13] and [14]. Murine eotaxin has marked synergism with IL-5. Anti-eotaxin and anti-IL-5 antibodies alone and in combination have been shown see more to reduce OVA-induced airway eosinophilia but failed to inhibit AHR [15]. Importantly, blocking eosinophil-activity in mice prevents allergen induced airway eosinophilia and AHR and results in reduced lung-fibrosis, a severe consequence of asthma [16] and [17]. For humans, therapeutic intervention strategies aimed at blocking the action of eosinophils have been investigated in various asthma settings and eosinophilic disorders. Blockade of IL-5

with the humanized monoclonal antibody Mepolizumab has reduced circulating and

sputum eosinophils and shown evidence for an effect on airway remodelling [17] but, has failed to achieve discernable effects on AHR or the late asthmatic response. Recent clinical testing of Mepolizumab in refractory eosinophilic asthma and prednisone dependent asthma has shown decreases in blood and sputum eosinophils and statistically significant decreases in the number of asthma exacerbations many [18] and [19]. Thus, anti-eosinophil strategies may be a promising therapy in asthma subgroups with heavy eosinophilic loads in which conventional anti-inflammatory therapy is only partially effective. Monoclonal antibodies (mAbs) are highly active molecules that are currently used in a numerous disease indications, including cancer and inflammation. However, due to the high amounts of antibodies required and their generally short half-life, therapies involving monoclonal antibodies are costly. In addition, long-term treatment with mAbs may result in the development of neutralizing anti-antibodies, which may reduce their efficacy or induce inhibitors adverse effects [20]. Active immunization against self-antigens typically results in relatively long-lived antibody responses and has been viewed as a potential alternative to mAb therapies. It has previously been shown that highly repetitive antigens displayed on viral surfaces are able to efficiently overcome B cell unresponsiveness [21].

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Its contents are solely the responsibility of the authors and do

Its contents are solely the responsibility of the authors and do not necessarily represent the official views of ASPR/HHS. Some of the described activities have been performed in the frame of the FP7 TRANSVAC and PHARVAT projects, which are funded by the European Commission,

and the authors would like to acknowledge the contributions of their colleagues from the TRANSVAC and PHARVAT Consortia. “
“The Institute of Experimental Medicine (IEM), founded in 1890, is one of the oldest scientific institutes in Russia. It was here in the Department of Virology that Academician Smorodintsev first developed live viral vaccines LY2157299 datasheet against polio, measles, mumps and influenza. Live attenuated influenza vaccines (LAIVs) generated by IEM have been used in Russia in adults since 1980 and in all age groups since

1987. To date, more than 100 million doses of LAIV have been used in the country for protection against seasonal influenza. Production of LAIV is based on the classic reassortment methodology, i.e. six genes from an attenuated donor backbone strain are combined with the genes coding for the haemagglutinin (HA) and the neuraminidase (NA) of circulating influenza virus strains. LAIVs are temperature sensitive with limited growth at 39–40 °C in ovo and thus cold adapted (ca) “donor strains” are used due to their growth ability at reduced temperature such Quizartinib as Libraries occurs in the human upper respiratory tract. Currently, all licensed LAIVs are produced in embryonated eggs, although some manufacturers are in advanced

stages of new generation cell-based LAIV development [1]. From 1997, when highly pathogenic avian influenza viruses began to circulate in Asia, IEM concentrated on the development of candidate pandemic LAIV. The first pandemic candidate H5N2 was registered in Russia in 2008. Further developments relating to H5N1, H7, H9 and H2 are in progress within a collaborative agreement with MycoClean Mycoplasma Removal Kit PATH who provided funds for these studies. The high case-fatality rates caused by outbreaks of H5N1 in 2004 highlighted the huge shortfall in global influenza vaccine production capacity in the event of a pandemic. A major initiative launched by the World Health Organization (WHO) to meet the Global Pandemic Influenza Action Plan [2] objective to increase vaccine supply involved the transfer of influenza vaccine production technology to developing countries. A comprehensive review of influenza vaccine technologies was thus commissioned to select the most appropriate technologies for the capacity building project [3]. It was concluded that while egg-based inactivated influenza vaccine (IIV) was the most widely used, the high capital investment required for industrial-scale operations may be difficult to justify in countries with limited market for seasonal vaccine. For pandemic surge capacity, egg-based LAIV had clear advantages over IIV with its significantly higher yield, faster quality control release, needle-free and potential single dose delivery, and cross-protection.

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