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Avian metapneumovirus (aMPV) is a highly contagious pathogen that causes acute upper respiratory tract diseases in chickens and turkeys, resulting in serious economic losses. Subtype B aMPV has recently become the dominant epidemic strain in China. We developed an attenuated aMPV subtype B strain by serial passaging in Vero cells and evaluated its safety and efficacy as a vaccine candidate. The safety test showed that after the 30th passage, the LN16-A strain was fully attenuated, as clinical signs of infection and histological lesions were absent after inoculation. The LN16-A strain did not revert to a virulent strain after five serial passages in chickens. The genomic sequence of LN16-A differed from that of the parent wild-type LN16 (wtLN16) strain and had nine amino acid mutations. In chickens, a single immunization with LN16-A induced robust humoral and cellular immune responses, including the abundant production of neutralizing antibodies, CD4+ T lymphocytes, and the Th1 (IFN-γ) and Th2 (IL-4 and IL-6) cytokines. We also confirmed that LN16-A provided 100% protection against subtype B aMPV and significantly reduced viral shedding and turbinate inflammation. Our findings suggest that the LN16-A strain is a promising live attenuated vaccine candidate that can prevent infection with subtype B aMPV.

This short paper on yellow head virus Type-1 (YHV-1) of shrimp describes preliminary research on the potential for using YHV-1 attenuated in insect cells to protect shrimp against yellow head disease (YHD). YHV-1 can cause severe mortality in the cultivated shrimp Penaeus (Penaeus) monodon and Penaeus (Litopenaeus) vannamei. No practical vaccination has been reported. The C6/36 mosquito cell cultures inoculated with YHV-1 become positive by PCR and by immunocytochemistry (immunopositive) for up to 30 split-cell passages. Shrimp injected with homogenates from low-passage cultures die from typical YHV-1 disease while shrimp injected with homogenates from high passage cultures do not, even though they become PCR positive and immunopositive for YHV-1. This suggested that viral attenuation had occurred during insect-cell passaging, and it opened the possibility of using homogenates from high-passage insect cultures as a vaccine against YHV-1. To test this hypothesis, homogenates from 30th-passage, YHV-positive cultures were injected into shrimp followed by challenge with virulent YHV-1. Controls were injected with homogenate from 30th-passage, naive (normal stock) insect-cell cultures. No shrimp mortality occurred following injection of either homogenate, but shrimp injected with the YHV-1 homogenate became both RT-PCR positive and immunopositive. Upon challenge 10 days later with YHV-1, mortality in shrimp injected with naive insect-cell homogenate was 100% within 7 days post-challenge while 100% mortality in the YHV-1 homogenate group did not occur until day 9 post-challenge. Kaplan-Meier log-rank survival analysis revealed that survival curves for the two groups were significantly different (p

With the rapidly increasing demand for poultry products and the current challenges facing the poultry industry, the application of biotechnology to enhance poultry production has gained growing significance. Biotechnology encompasses all forms of technology that can be harnessed to improve poultry health and production efficiency. Notably, biotechnology-based approaches have fueled rapid advances in biological research, including (a) genetic manipulation in poultry breeding to improve the growth and egg production traits and disease resistance, (b) rapid identification of infectious agents using DNA-based approaches, (c) inclusion of natural and synthetic feed additives to poultry diets to enhance their nutritional value and maximize feed utilization by birds, and (d) production of biological products such as vaccines and various types of immunostimulants to increase the defensive activity of the immune system against pathogenic infection. Indeed, managing both existing and newly emerging infectious diseases presents a challenge for poultry production. However, recent strides in vaccine technology are demonstrating significant promise for disease prevention and control. This review focuses on the evolving applications of biotechnology aimed at enhancing vaccine immunogenicity, efficacy, stability, and delivery.

Abstract Background Histomonas meleagridis is a protozoan parasite and the causative agent of histomonosis, an important poultry disease whose significance is underlined by the absence of any treatment and prophylaxis. The recent successful in vitro attenuation of the parasite urges questions about the underlying mechanisms. Results Whole genome sequence data from a virulent and an attenuated strain originating from the same parental lineage of H. meleagridis were recruited using Oxford Nanopore Technology (ONT) and Illumina platforms, which were combined to generate megabase-sized contigs with high base-level accuracy. Inspecting the genomes for differences identified two substantial deletions within a coding sequence of the attenuated strain. Additionally, one single nucleotide polymorphism (SNP) and indel targeting coding sequences caused the formation of premature stop codons, which resulted in the truncation of two genes in the attenuated strain. Furthermore, the genome of H. meleagridis was used for characterizing protein classes of clinical relevance for parasitic protists. The comparative analysis with the genomes of Trichomonas vaginalis, Tritrichomonas foetus and Entamoeba histolytica identified ~ 2700 lineage-specific gene losses and 9 gene family expansions in the H. meleagridis lineage. Conclusions Taken as a whole, the obtained data provide the first hints to understand the molecular basis of attenuation in H. meleagridis and constitute a genomics platform for future research on this important poultry pathogen.

The rising cost of oncological drugs poses a global challenge to patients, insurers, and policy makers, with the leading drugs worldwide by revenue from immune checkpoint inhibitors (ICIs). Despite its cost, ICI is marked as a paradigm shift, offering the potential of a long-term cure. To reduce cost, an attenuated dose of ICI based on pharmacological principles can be used while maintaining efficacy. This real-world study aims to examine the prescribing patterns, the effect of financial constraints, and the outcomes in non-small cell lung cancer (NSCLC). All patients receiving palliative intent ICI treatment for advanced NSCLC between January 2014 and April 2021 in National University Hospital, Singapore were recruited. Demographics, prescription trends, factors affecting the prescription of attenuated dose ICI (AD ICI) versus standard dose ICI (SD ICI), and the effect of dose on survival outcomes, toxicities, and costs were examined. Two hundred seventy-four received ICI. The majority of them were treated in first-line setting. One hundred sixty-two (59%) of patients received AD ICI, whereas 112 (41%) received SD ICI. Patients who did not have a supplemental private as-charged health insurance plan were more likely to have received AD ICI (OR: 4.53 [2.69–7.61] p < 0.001). There was no difference in progression-free survival (PFS) and overall survival (OS)—adjusted HR 1.07 CI [0.76, 1.50] p = 0.697 and HR 0.95 CI [0.67, 1.34] p = 0.773, respectively, between patients who received AD versus SD ICI. A cost minimization analysis evaluating the degree of cost savings related to drug costs estimated a within study cost saving of USD 7,939,059 over 7 years. Our study provides evidence for AD-ICI as a promising strategy to maximize the number of patients who can be treated with ICI. This has the potential to make significant economic impact and allow more patients to benefit from novel therapies.

Metinleri cümleler, cümleleri ise kelimeler oluşturmaktadır. Kelime-lerin türlerinden biri de Arap dili literatüründe “hurûf-u meâni” diye isimlendirilen edatlardır. Arapça metinlere bakıldığında hemen hemen her cümle ve her satırda bu edatlara rastlamak mümkündür. Bu da edatların manaya katkısının ne denli önemli olduğuna işaret etmektedir. Cümle içerisindeki konumuna bağlı olarak gerek i‘rab, gerekse mana itibariyle değişkenlik arz eden edatlar, Arap dilbilimcilerinin bakış açısına ve yoruma dayalı olarak tartışmaya konu olmuş ve bu bağlamda sorun hale gelmiştir. Bu makalenin amacı, söz konusu edatlardan biri olan “en” edatının işleviyle ilgili olarak öne sürülen görüşleri ve görüş ayrılığından kaynaklanan problemleri irdelemektir. Bu hedef doğrultusunda önce “en” edatının harf mi isim mi? Şeklindeki sorunun çözümüne çalışılacak, daha sonra bu edatın cümledeki pozisyonuna göre ne tür manalara geldiği ya da cümleye ne gibi anlam kazandırdığı üzerinde durulacaktır.

Introduction: Fowl adenoviruses (FAdV) cause inclusion body hepatitis (IBH) in chickens and new vaccination strategies against IBH are needed as an effective control measure in the poultry industry. Methods: The attenuated FAdV isolates from from chicken embryonated (UPM1137E20) and cell culture (UPM1137CEL35) were evaluated and compared based on sequence analysis of hexon and fiber genes. Their pathogenicities and immunogenicities were then determined in the commercial broiler chickens. Groups of chicken were inoculated with 0.5ml chicken-embryonated-derived attenuated FAdV isolates via oral and IP routes and sera, trachea, liver and gizzard samples were collected at days 3, 7, 14 and 21post-inoculation. Results: Molecular analysis revealed both isolates had 99.1% and 97.3% homologies in the L1 loop region of hexon gene and knob region of fiber gene, respectively. Molecular changes in UPM1137E20 were prominent in the knob of fiber gens with 3 amino acid changes, while for UPM1137CEL35, notable in the L1 loop region with 3 amino acid changes. It was demonstrated that both attenuated isolates are non-pathogenic and safe in commercial broiler chickens. Neither gross nor histopathological lesions were recorded in all tested groups. Both isolates induced high antibody response significantly via intraperitoneal route when compared to the control. Conclusion: UPM1137E20 isolate had a high potential to be further evaluated as a live attenuated vaccine against viral poultry diseases such as IBH.

ABSTRACT Influenza A viruses (IAV) remain emerging threats to human public health. Live-attenuated influenza vaccines (LAIV) are one of the most effective prophylactic options to prevent disease caused by influenza infections. However, licensed LAIV remain restricted for use in 2- to 49-year-old healthy and nonpregnant people. Therefore, development of LAIV with increased safety, immunogenicity, and protective efficacy is highly desired. The U.S.-licensed LAIV is based on the master donor virus (MDV) A/Ann Arbor/6/60 H2N2 backbone, which was generated by adaptation of the virus to growth at low temperatures. Introducing the genetic signature of the U.S. MDV into the backbone of other IAV strains resulted in varying levels of attenuation. While the U.S. MDV mutations conferred an attenuated phenotype to other IAV strains, the same amino acid changes did not significantly attenuate the pandemic A/California/04/09 H1N1 (pH1N1) strain. To attenuate pH1N1, we replaced the conserved leucine at position 319 with glutamine (L319Q) in PB1 and analyzed the in vitro and in vivo properties of pH1N1 viruses containing either PB1 L319Q alone or in combination with the U.S. MDV mutations using two animal models of influenza infection and transmission, ferrets and guinea pigs. Our results demonstrated that L319Q substitution in the pH1N1 PB1 alone or in combination with the mutations of the U.S. MDV resulted in reduced pathogenicity (ferrets) and transmission (guinea pigs), and an enhanced temperature sensitive phenotype. These results demonstrate the feasibility of generating an attenuated MDV based on the backbone of a contemporary pH1N1 IAV strain. IMPORTANCE Vaccination represents the most effective strategy to reduce the impact of seasonal IAV infections. Although LAIV are superior in inducing protection and sterilizing immunity, they are not recommended for many individuals who are at high risk for severe disease. Thus, development of safer and more effective LAIV are needed. A concern with the current MDV used to generate the U.S.-licensed LAIV is that it is based on a virus isolated in 1960. Moreover, mutations that confer the temperature-sensitive, cold-adapted, and attenuated phenotype of the U.S. MDV resulted in low level of attenuation in the contemporary pandemic A/California/04/09 H1N1 (pH1N1). Here, we show that introduction of PB1 L319Q substitution, alone or in combination with the U.S. MDV mutations, resulted in pH1N1 attenuation. These findings support the development of a novel LAIV MDV based on a contemporary pH1N1 strain as a medical countermeasure against currently circulating H1N1 IAV.

Summary: Zika virus (ZIKV) is an Aedes-mosquito-borne flavivirus that causes debilitating congenital and developmental disorders. Improved understanding of ZIKV pathogenesis could assist efforts to fill the therapeutic and vaccine gap. We use several ZIKV strains, including a pair differing by a single phenylalanine-to-leucine substitution (M-F37L) in the membrane (M) protein, coupled with unbiased genomics to demarcate the border between attenuated and pathogenic infection. We identify infection-induced metabolic dysregulation as a minimal set of host alterations that differentiates attenuated from pathogenic ZIKV strains. Glycolytic rewiring results in impaired oxidative phosphorylation and mitochondrial dysfunction that trigger inflammation and apoptosis in pathogenic but not attenuated ZIKV strains. Critically, pyruvate supplementation prevents cell death, in vitro, and rescues fetal development in ZIKV-infected dams. Our findings thus demonstrate dysregulated metabolism as an underpinning of ZIKV pathogenicity and raise the potential of pyruvate supplementation in expectant women as a prophylaxis against congenital Zika syndrome.

The 5’ end of the flavivirus genome contains a type 1 cap structure formed by sequential N-7 and 2’-O methylations by viral methyltransferase (MTase). Cap methylation of flavivirus genome is an essential structural modification to ensure the normal proliferation of the virus. Tembusu virus (TMUV) (genus Flavivirus) is a causative agent of duck egg drop syndrome and has zoonotic potential. Here, we identified the in vitro activity of TMUV MTase and determined the effect of K61-D146-K182-E218 enzymatic tetrad on N-7 and 2’-O methylation. The entire K61-D146-K182-E218 motif is essential for 2’-O MTase activity, whereas N-7 MTase activity requires only D146. To investigate its phenotype, the single point mutation (K61A, D146A, K182A or E218A) was introduced into TMUV replicon (pCMV-Rep-NanoLuc) and TMUV infectious cDNA clone (pACYC-TMUV). K-D-K-E mutations reduced the replication ability of replicon. K61A, K182A and E218A viruses were genetically stable, whereas D146A virus was unstable and reverted to WT virus. Mutant viruses were replication and virulence impaired, showing reduced growth and attenuated cytopathic effects and reduced mortality of duck embryos. Molecular mechanism studies showed that the translation efficiency of mutant viruses was inhibited and a higher host innate immunity was induced. Furthermore, we found that the translation inhibition of MTase-deficient viruses was caused by a defect in N-7 methylation, whereas the absence of 2’-O methylation did not affect viral translation. Taken together, our data validate the debilitating mechanism of MTase-deficient avian flavivirus and reveal an important role for cap-methylation in viral translation, proliferation, and escape from innate immunity.

Non-typhoidal Salmonella (NTS) is a major cause of gastroenteritis and is responsible for approximately 93 million cases annually. In healthy individuals, gastroenteritis caused by NTS is usually self-limiting, however, NTS can cause severe invasive disease in immunocompromised patients. Very little research has been directed towards development of vaccines against Salmonella serogroups O:6,7 or O:8. We have constructed a live attenuated serogroup O:8 vaccine, CVD 1979, by deleting guaBA, htrA, and aroA from the genome of S. Newport. We have shown that the candidate vaccine is well tolerated in mice and elicits serum immunoglobulin G (IgG) antibodies against core O-polysaccharide (COPS) when administered orally. Immunized mice were challenged intraperitoneally with wild-type S. Newport and bacterial burden in the liver and spleen was found to be significantly reduced in the livers of immunized mice compared to control mice. We also observed moderate vaccine efficacy (45%) against lethal challenge with the serogroup O:8 serovar, S. Muenchen, but low vaccine efficacy (28%) following lethal challenge with a serogroup O:6,7 serovar, S. Virchow. In vitro, we have shown that antibodies generated by CVD 1979 only recognize lipopolysaccharide (LPS) from serogroup O:8 but not serogroup O:6,7 serovars, and that they mediate opsonophagocytic antibody (OPA) activity against serogroup O:8 but not serogroup O:6,7 serovars. We also showed that OPA activity can be blocked by pre-incubating the antisera with serogroup O:8 lipopolysaccharide. Taken together, our data demonstrate that we have constructed a well-tolerated, effective live attenuated S. Newport vaccine which elicits functional antibodies against serogroup O:8 but not O:6,7 serovars.

The poxvirus, myxoma virus (MYXV) has shown efficacy as an oncolytic virus (OV) in some cancer models. However, MYXV replication within murine cancer models and spontaneous canine sarcomas is short-lived. In mice, successful treatment of tumors requires frequent injections with MYXV. We hypothesize that treatment of cancer with a recombinant MYXV that promotes apoptosis could improve the efficacy of MYXV. The orfC gene of walleye dermal sarcoma virus (WDSV), which induces apoptosis, was recombined into the MYXV genome (MYXVorfC). A marked increase in apoptosis was observed in cells infected with MYXVorfC. To ensure that expression of WDSV orfC by MYXV does not potentiate the pathogenesis of MYXV, we evaluated the effects of MYXVorfC inoculation in the only known host of MYXV, New Zealand white rabbits. Virus dissemination in rabbit tissues was similar for MYXVorfC and MYXV. Virus titers recovered from tissues were lower in MYXVorfC-infected rabbits as compared to MYXV-infected rabbits. Importantly, rabbits infected with MYXVorfC had a delayed onset of clinical signs and a longer median survival time than rabbits infected with MYXV. This study indicates that MYXVorfC is attenuated and suggests that MYXVorfC will be safe to use as an OV therapy in future studies.

Inactivated whole-virus vaccines are widely used for the control of foot-and-mouth disease (FMD). Their production requires the growth of large quantities of virulent FMD virus in biocontainment facilities, which is expensive and carries the risk of an inadvertent release of virus. Attenuated recombinant viruses lacking the leader protease coding region have been proposed as a safer alternative for the production of inactivated FMD vaccines (Uddowla et al., 2012, J Virol 86:11675-85). In addition to the leader deletion, the marker vaccine virus FMDV LL3BPVKV3DYR A24 encodes amino acid substitutions in the viral proteins 3B and 3D that allow the differentiation of infected from vaccinated animals and has been previously shown to be effective in cattle and pigs. In the present study, two groups of six pigs each were inoculated with live FMDV LL3BPVKV3DYR A24 virus either intradermally into the heel bulb (IDHB) or by intra-oropharyngeal (IOP) deposition. The animals were observed for 3 or 5 days after inoculation, respectively. Serum, oral and nasal swabs were collected daily and a thorough postmortem examination with tissue collection was performed at the end of the experiment. None of the animals had any signs of disease or virus shedding. Virus was reisolated from only one serum sample (IDHB group, sample taken on day 1) and one piece of heel bulb skin from the inoculation site of another animal (IDHB group, necropsy on day 3), confirming that FMDV LL3BPVKV3DYR A24 is highly attenuated in pigs.

Deaths associated with tuberculosis (TB) is rising and accounted for 1.4 million deaths in 2015 many of which were due to drug-resistant bacteria. Vaccines represent an important medical intervention, but the current Bacilli Calmette-Guerin (BCG) vaccine is not ideal for the protection of teenagers and adults. Therefore, a safe and effective vaccine is urgently needed. In this study, we designed a novel vaccine using an attenuated Listeria monocytogenes strain carrying fusion antigen FbpB-ESAT-6 (rLM) and characterized its safety and protective efficacy against Mycobacterium tuberculosis (M.tb) infection in mice. Compared to the wild type strain yzuLM4 and parental strain LMΔactA/plcB (LM1-2), the virulence of rLM was significantly reduced as judged by its infectious kinetics and LD50 dose. Further characterization of intravenous immunization showed that prime-boost vaccination significantly increased the levels of Th1 cytokines (IFN-γ, IL-17, and IL-6), and enhanced cytotoxic T lymphocyte (CTL) CTLs activity, suggesting that rLM could elicit potent Th1/Th17 responses. More importantly, rLM significantly conferred the protection against M.tb H37Rv challenge. Collectively, our findings indicated that rLM is a novel and useful tool to prevent M.tb infection, and can be potentially be used to boost BCG-primed immunity.

The present study aimed at investigation on developing the immune response against Toxoplasmosis in Swiss Albino mice of the species Mus musculus, BALB/c strain, which were infected, experimentally, with Toxoplasma gondii in order to render the host able to resist any infection with this disease in the future. To achieve this, Toxoplasma gondii tissue cysts, collected from placenta of aborted women, they attenuated by irradiation with two absorbed doses of X-Ray irradiation 0.4 and 0.8 KGy. Mice were injected, intraperitoneally with tissue cysts at a rate of 100 cysts/mice single or double doses. In addition, groups of mice were injected with non-irradiated tissue cysts, as a positive control groups. The criteria used in the present study was humoral immunity, represented by IgM using Enzyme–Linked Immunosorbent Assay (ELISA IgM) to demonstrate the differentiated in IgM level between mice inoculated with X-Ray irradiated tissue cysts and positive control groups, which infected with non-irradiated tissue cysts. The result shown that the immunization with X-Ray irradiated Toxoplasma gondii tissue cysts could partially protect the mice from Toxoplasma gondii infection, and produce specific IgM antibody.

In a trial for comparison between the efficiency of single fowl pox (FP) vaccination and the efficiency of each combined FP and Avian encephalomyelitis (AE) vaccination and simultaneous vaccination with FP and Reo and with FP and Chicken anemia virus (CAV) vaccines our conclusion was that there is no antagonistic reaction between FP virus strain and each AE, Reo and CA viruses strains. In addition, humoral immune response against AE virus strain in case of combined AE+FP vaccination is markedly potent than that in case of single AE vaccination, more over the value of average EID50 of AE virus strain in several batches of combined AE+FP vaccines is significantly higher at P > 0.05 than that in several batches of single AE vaccines. On the other hand, immune response against FP virus strain and Reo virus strain in case of simultaneous vaccination with FP and Reo vaccines is higher than that in case of single FP vaccination and single Reo vaccination. Consequently, it is advisable to use combined live attenuated AE+FP vaccine instead of vaccination with single FP and AE separately. Also, application of simultaneous vaccination with FP and Reo vaccines is advisable as it is proved to be more beneficial than vaccination with each vaccine separately specially in case of that FP vaccine of low potency.

Live attenuated influenza vaccines (LAIV) have prevented morbidity and mortality associated with influenza viral infections for many years and represent the best therapeutic option to protect against influenza viral infections in humans. However, the development of LAIV has traditionally relied on empirical methods, such as the adaptation of viruses to replicate at low temperatures. These approaches require an extensive investment of time and resources before identifying potential vaccine candidates that can be safely implemented as LAIV to protect humans. In addition, the mechanism of attenuation of these vaccines is poorly understood in some cases. Importantly, LAIV are more efficacious than inactivated vaccines because their ability to mount efficient innate and adaptive humoral and cellular immune responses. Therefore, the design of potential LAIV based on known properties of viral proteins appears to be a highly appropriate option for the treatment of influenza viral infections. For that, the viral RNA synthesis machinery has been a research focus to identify key amino acid substitutions that can lead to viral attenuation and their use in safe, immunogenic, and protective LAIV. In this review, we discuss the potential to manipulate the influenza viral RNA-dependent RNA polymerase (RdRp) complex to generate attenuated forms of the virus that can be used as LAIV for the treatment of influenza viral infections, one of the current and most effective prophylactic options for the control of influenza in humans.

The serologically diverse influenza A viruses, although transmissible among various susceptible species, mostly infect avian species. Avian influenza viruses (AIV) are also notorious for adapting to mammalian species, including humans. Although eradication of commercial birds infected with AIV is the preferred method of control, the ever presence of potential avian migratory, reservoir species makes worldwide spread inevitable and vaccine development a high priority for poultry. Live, attenuated vaccine strategies are of concern because of the potential of AIV to mutate, through point mutations and/or reassortment of their segmented genome. Both live and the safer, killed vaccines are of concern because of competition of natural and vaccine antigens in critical diagnostic assays. Subunit vaccines, which allow for protein distinction for diagnostic purposes, may consist of purified AIV protein or genes that encode individual viral proteins. Most vaccines have targeted the virus hemagglutinin protein, which is responsible for induction of the most effective neutralizing antibodies. Gene vaccines that include plasmid DNA and viral vector delivery of AIV genes allow for endogenous in vivo amplification of protein within cells. While fowlpox virus vectors have been licensed and proven to be efficacious even in field situations, other viral vectors that target the respiratory tract are in experimental development with promising practical application for poultry. Maximum exploitation of vectored vaccines may incorporate enhancing immune molecules.

In the present study, the humoral immune response developed following vaccination with the live-attenuated (Smithburn) Rift Valley fever (RVF) vaccine in sheep, goats, cattle, buffaloes and camels was investigated. Results showed that, serum neutralizing antibody titers of RVF virus started to appear in the sera of all vaccinated animals with live-attenuated Rift valley fever vaccine after the first week post-vaccination and reached its peak after the third month of vaccination. It persisted to be higher than the acceptable limit of protection (>40) in the sera of sheep and goats in more than 6 months post-vaccination while it declined in the sera of cattle, buffaloes and camels to become lower than the acceptable limit of protection (

In the second half of the twentieth century dengue spread throughout the tropics, threatening the health of a third of the world's population. Dengue viruses cause 50 -100 million cases of acute febrile disease every year, including more than 500 000 reported cases of the severe forms of the disease - dengue haemorrhagic fever and dengue shock syndrome. Attempts to create conventional vaccines have been hampered by the lack of suitable experimental models, the need to provide protection against all four serotypes simultaneously and the possible involvement of virus-specific immune responses in severe disease. The current understanding of dengue pathogenesis is outlined in this review, with special emphasis on the role of the immune response. The suspected involvement of the immune system in increased disease severity and vascular damage has raised concerns about every vaccine design strategy proposed so far. Clearly more research is needed on understanding the correlates of protection and mechanisms of pathogenesis. There is, however, an urgent need to provide a solution to the escalating global public health problems caused by dengue infections. Better disease management, vector control and improved public health measures will help reduce the current disease burden, but a safe and effective vaccine is probably the only long-term solution. Although concerns have been raised about the possible safety and efficacy of both conventional and novel vaccine technologies, the situation is now so acute that it is not possible to wait for the perfect vaccine. Consequently the careful and thorough evaluation of several of the current candidate vaccines may be the best approach to halting the spread of disease.

The main goal of this study was to evaluate the protective efficacy of living attenuated Salmonella Typhimurium (S. Typhimurium) vaccine in poultry and to evaluate its use in control of salmonella infection in chickens. Oral vaccination of chickens within 36 hours after hatching and after 6 weeks from the first dose induced a strong humoral immune response as measured by ELISA. Challenge test was done with virulent strain of S. Typhimurium. Shedding of S. Typhimurium was detected during the first day, but after 14 days, salmonella could not be detected in the internal organs of vaccinated chickens compared with the non-vaccinated challenged chickens.

Porcine epidemic diarrhea virus (PEDV), a predominant cause of acute enteric infection, leads to severe dehydrating diarrhea and mortality in piglets all over the world. A virulent PEDV YN13 strain, isolated in our laboratory, was attenuated to yield an attenuated PEDV strain YN144. To better understand the pathogenesis mechanism and the virus-host interaction during infection with both PEDV YN13 and YN144 strains, a comparative proteomic analysis was carried out to investigate the proteomic changes produced in the primary target organ, using isobaric tags for relative and absolute quantitation (iTRAQ) labeling, followed by liquid chromatography tandem-mass spectrometry (LC-MS/MS). A total of 269 and 301 differently expressed proteins (DEPs) were identified in the jejunum tissues of the piglets inoculated with YN13 and YN144, respectively. Bioinformatics analysis revealed that these proteins were involved in stress responses, signal transduction, and the immune system. All of these involved interferon-stimulated genes (ISGs) which were up-regulated in jejunums by both of the PEDV-infected groups. Based on the comparative analysis, we proposed that different changes induced by YN13 and YN144 in heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), eukaryotic initiation factor 4G1 (eIF4G1), and some members in the heat shock protein (HSP) family, may be responsible for differences in their pathogenicity.