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nursing in ireland: the guinea-pigs and the mansion house cat. 191729825405
artificial production of epilepsy in guineapigs. 187229639972
single dose rvsvδg-junvgp vaccine protects guinea pigs against lethal junin virus challenge.junin virus (junv) is a pathogen of biodefense importance due to its potential for aerosol transmission and mortality rates reaching 30%. currently, there are no junv vaccines licensed by the united states food and drug administration (fda) for at-risk individuals. a vaccine based on recombinant vesicular stomatitis virus (rvsv) has been effectively used to prevent ebola virus disease in humans. here, we evaluated the protective efficacy of a rvsv expressing the junv glycoprotein (rvsvδg-junvgp) ...202134373461
second-generation live-attenuated candid#1 vaccine virus resists reversion and protects against lethal junín virus infection in guinea pigs.live-attenuated virus vaccines are highly effective in preventing viral disease but carry intrinsic risks of residual virulence and reversion to pathogenicity. the classically derived candid#1 virus protects seasonal field workers in argentina against zoonotic infection by junín virus (junv) but is not approved in the united states, in part due to the potential for reversion at the attenuating locus, a phenylalanine-to-isoleucine substitution at position 427 in the gp2 subunit of the gpc envelop ...202133952638
therapy for argentine hemorrhagic fever in nonhuman primates with a humanized monoclonal antibody.the covid-19 pandemic has reemphasized the need to identify safe and scalable therapeutics to slow or reverse symptoms of disease caused by newly emerging and reemerging viral pathogens. recent clinical successes of monoclonal antibodies (mabs) in therapy for viral infections demonstrate that mabs offer a solution for these emerging biothreats. we have explored this with respect to junin virus (junv), an arenavirus classified as a category a high-priority agent and the causative agent of argenti ...202133836604
development of a reverse genetic system to generate recombinant chimeric tacaribe virus that expresses junín virus glycoproteins.mammarenaviruses are enveloped and segmented negative-stranded rna viruses that comprise several pathogenic members associated with severe human hemorrhagic fevers. tacaribe virus (tcrv) is the prototype for the new world group of mammarenaviruses and is not only naturally attenuated but also phylogenetically and antigenically related to all south american pathogenic mammarenaviruses, particularly the junín virus (junv), which is the etiological agent of argentinian hemorrhagic fever (ahf). more ...202033203040
lassa virus vaccine candidate ml29 generates truncated viral rnas which contribute to interfering activity and attenuation.defective interfering particles (dips) are naturally occurring products during virus replication in infected cells. dips contain defective viral genomes (dvgs) and interfere with replication and propagation of their corresponding standard viral genomes by competing for viral and cellular resources, as well as promoting innate immune antiviral responses. consequently, for many different viruses, including mammarenaviruses, dips play key roles in the outcome of infection. due to their ability to b ...202133573250
chadox1-vectored lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal lassa virus challenge.lassa virus (lasv) infects hundreds of thousands of individuals each year, highlighting the need for the accelerated development of preventive, diagnostic, and therapeutic interventions. to date, no vaccine has been licensed for lasv. chadox1-lassa-gpc is a chimpanzee adenovirus-vectored vaccine encoding the josiah strain lasv glycoprotein precursor (gpc) gene. in the following study, we show that chadox1-lassa-gpc is immunogenic, inducing robust t-cell and antibody responses in mice. furthermor ...202133654106
porcine circovirus 2 capsid protein produced in n. benthamiana forms virus-like particles that elicit production of virus-neutralizing antibodies in guinea pigs.porcine circovirus type 2 (pcv2) is a non-enveloped, icosahedral virus of the circoviridae family, with a small, circular, single-stranded dna genome. pcv2 infections cause substantial economic losses in the pig industry worldwide. currently, commercially produced pcv2 vaccines are expensive, whereas plant-based expression systems can produce recombinant proteins at low cost for use as vaccines. in this study, recombinant pcv2 capsid protein (rcap) was transiently expressed in nicotiana benthami ...202133667631
immunogenic potential of dna vaccine candidate, zycov-d against sars-cov-2 in animal models.severe acute respiratory syndrome coronavirus 2 (sars-cov-2), initially originated in china in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. huge efforts were undertaken to bring the covid-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. we developed a candidate vaccine zycov-d comprising of a dna plasmid vector carrying the gene e ...202134120764
zika virus and host interactions: from the bench to the bedside and beyond.before the emergence of sars-cov-2 (severe acute respiratory syndrome coronavirus 2), the causative agent of the current covid-19 (coronavirus disease 2019) pandemic [...].202033198165
immunogenicity and protective efficacy of a highly thermotolerant, trimeric sars-cov-2 receptor binding domain derivative.the receptor binding domain (rbd) of sars-cov-2 is the primary target of neutralizing antibodies. we designed a trimeric, highly thermotolerant glycan engineered rbd by fusion to a heterologous, poorly immunogenic disulfide linked trimerization domain derived from cartilage matrix protein. the protein expressed at a yield of ∼80-100 mg/l in transiently transfected expi293 cells, as well as cho and hek293 stable cell lines and formed homogeneous disulfide-linked trimers. when lyophilized, these p ...202134260218
the antigenicity of epidemic sars-cov-2 variants in the united kingdom.to determine whether the neutralization activity of monoclonal antibodies, convalescent sera and vaccine-elicited sera was affected by the top five epidemic sars-cov-2 variants in the uk, including d614g+l18f+a222v, d614g+a222v, d614g+s477n, voc-202012/01(b.1.1.7) and d614g+69-70del+n439k, a pseudovirus-neutralization assay was performed to evaluate the relative neutralization titers against the five sars-cov-2 variants and 12 single deconvolution mutants based on the variants. in this study, 18 ...202134220844
lopsided blood-thinning drug increases the risk of internal flow choking leading to shock wave generation causing asymptomatic cardiovascular disease.the discovery of sanal flow choking in the cardiovascular-system calls for multidisciplinary and global action to develop innovative treatments and to develop new drugs to negate the risk of asymptomatic-cardiovascular-diseases. herein, it is shown that when blood-pressure-ratio (bpr) reaches the lower-critical-hemorrhage-index (lchi) internal-flow-choking and shock wave generation can occur in the cardiovascular-system, with sudden expansion/divergence/vasospasm or bifurcation regions, without ...202133728053
multivalent dna vaccines as a strategy to combat multiple concurrent epidemics: mosquito-borne and hemorrhagic fever viruses.the emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. outbreaks of ebola, lassa, and marburg viruses in overlapping regions of central and west africa and the co-circulation of zika, dengue, and chikungunya viruses in areas with a. aegypti mosquitos highlight the need for a rapidly deployable, safe, and versatile vaccine platform readily available to respond. the dna vaccine platform stands out as such an applica ...202133673603
guinea pig cytomegalovirus protective t cell antigen gp83 is a functional pp65 homolog for innate immune evasion and pentamer dependent virus tropism.the guinea pig is the only small animal model for congenital cmv but requires species-specific guinea pig cytomegalovirus (gpcmv). tegument protein gp83 is the presumed homolog of hcmv pp65 but gene duplication in the ul82-ul84 homolog locus in various animal cmv made it unclear if gp83 was a functional homolog. a gp83 null deletion mutant gpcmv (gp83dpc+) generated in the backdrop of glycoprotein pentamer complex (pc) positive virus, required for non-fibroblast infection, had normal growth kine ...202133658350
the placental response to guinea pig cytomegalovirus depends upon the timing of maternal infection.human cytomegalovirus (hcmv) infects the placenta, and these placental infections can cause fetal injury and/or demise. the timing of maternal hcmv infection during pregnancy is a determinant of fetal outcomes, but how development affects the placenta's susceptibility to infection, the likelihood of placental injury post-infection, and the frequency of transplacental hcmv transmission remains unclear. in this study, guinea pig cytomegalovirus (gpcmv) was used to model primary maternal infection ...202134211475
a trimeric capable gb cmv vaccine provides limited protection against a highly cell associated and epithelial tropic strain of cytomegalovirus in guinea pigs.multiple strains of human cytomegalovirus (hcmv) can cause congenital cytomegalovirus (ccmv) by primary or secondary infection. the viral gb glycoprotein is a leading vaccine candidate, essential for infection of all cell-types, and immunodominant antibody target. guinea pig cytomegalovirus (gpcmv) is the only small animal model for ccmv. various gb vaccines have shown efficacy but studies have utilized truncated gb and protection against prototype strain 22122 with preferential tropism to fibro ...202133729125
the guinea pig cytomegalovirus gp119.1 gene encodes an igg-binding glycoprotein that is incorporated into the virion.cytomegaloviruses (cmvs) encode various immunoevasins, including viral receptors for the fc domain of host igg (vfcγr), to evade host immune responses. although guinea pig cmv (gpcmv) provides a useful animal model for congenital cmv infection, the gpcmv genes encoding such receptors have not yet been characterized. in this study, we analyzed a locus that may encode gene products for the gpcmv immune evasion mechanisms and identified the following. (a) race analyses identified four transcripts i ...202133616978
pathogenicity and transmissibility assessment of two strains of human influenza virus isolated in china in 2018.influenza season occurs every year in china, but its presentation was unusual in the period from december 2017 to early 2018. during this period, influenza activity was increasing across the country and was much greater than during the same period in previous years, with great harm to people's health.202133472481
assessment of two novel live-attenuated vaccine candidates for herpes simplex virus 2 (hsv-2) in guinea pigs.treatment to ameliorate the symptoms of infection with herpes simplex virus 2 (hsv-2) and to suppress reactivation has been available for decades. however, a safe and effective preventative or therapeutic vaccine has eluded development. two novel live-attenuated hsv-2 vaccine candidates (rvx201 and rvx202) have been tested preclinically for safety. hartley guinea pigs were inoculated vaginally (n = 3) or intradermally (n = 16) with either vaccine candidate (2 × 107 pfu) and observed for disease ...202133805768
h9n2 influenza virus spillover into wild birds from poultry in china bind to human-type receptors and transmit in mammals via respiratory droplets.h9n2 influenza virus has been reported worldwide for several decades, and it has evolved into multiple genotypes among domestic poultry. however, the study involving ecology and evolution of low pathogenic avian influenza virus h9n2 in wild birds in china is limited. here, we carried out surveillance of avian influenza virus h9n2 in wild birds along with the east asian-australian migratory flyway in china in 2017. to estimate the prevalence of h9n2 avian virus in wild birds, information on expos ...202133566453
pathogenicity and transmissibility of current h3n2 swine influenza virus in southern china: a zoonotic potential.swine are considered as 'mixing vessels' of influenza a viruses and play an important role in the generation of novel influenza pandemics. in this study, we described that the h3n2 swine influenza (swh3n2) viruses currently circulating in pigs in guangdong province carried six internal genes from 2009 pandemic h1n1 virus (pmd09), and their antigenicity was obviously different from that of current human h3n2 influenza viruses or recommended vaccine strains (a/guangdong/1194/2019, a/hong kong/4801 ...202134132051
n-glycolylneuraminic acid in animal models for human influenza a virus.the first step in influenza virus infection is the binding of hemagglutinin to sialic acid-containing glycans present on the cell surface. over 50 different sialic acid modifications are known, of which n-acetylneuraminic acid (neu5ac) and n-glycolylneuraminic acid (neu5gc) are the two main species. animal models with α2,6 linked neu5ac in the upper respiratory tract, similar to humans, are preferred to enable and mimic infection with unadapted human influenza a viruses. animal models that are c ...202134062844
pb1 s524g mutation of wild bird-origin h3n8 influenza a virus enhances virulence and fitness for transmission in mammals.influenza h3n8 viruses have been recovered frequently from wild bird species, including anseriformes (primarily from migratory ducks) and charadriiformes (primarily from shorebirds). however, little attention has been given to the transmission ability of h3n8 avian influenza viruses among mammals. here, we study the potential human health threat and the molecular basis of mammalian transmissibility of h3n8 avian influenza viruses isolated from wild bird reservoirs. we classified eight h3n8 virus ...202133840358
avian influenza a viruses reassort and diversify differently in mallards and mammals.reassortment among co-infecting influenza a viruses (iavs) is an important source of viral diversity and can facilitate expansion into novel host species. indeed, reassortment played a key role in the evolution of the last three pandemic iavs. observed patterns of reassortment within a coinfected host are likely to be shaped by several factors, including viral load, the extent of viral mixing within the host and the stringency of selection. these factors in turn are expected to vary among the di ...202133808674
a quantitative approach to assess influenza a virus fitness and transmission in guinea pigs.efforts to estimate the risk posed by potentially pandemic influenza a viruses (iav), and to understand the mechanisms governing interspecies transmission, have been hampered by a lack of animal models that yield relevant and statistically robust measures of viral fitness. to address this gap, we monitored several quantitative measures of fitness in a guinea pig model: infectivity, magnitude of replication, kinetics of replication, efficiency of transmission, and kinetics of transmission. with t ...202133731462
molecular characteristics, antigenicity, pathogenicity, and zoonotic potential of a h3n2 canine influenza virus currently circulating in south china.canine influenza viruses (civs) could be a source of influenza viruses which infect humans because canine are important companion pets. to assess the potential risk of h3n2 civs currently circulating in southern china to public health, biological characteristics of a/canine/guangdong/dy1/2019 (cady1/2019) were detected. cady1/2019 bound to both avian-type and human-type receptors. cady1/2019 had a similar ph value for ha protein fusion to human viruses, but its antigenicity was obviously differe ...202133767679
a new candidate vaccine for human brucellosis based on influenza viral vectors: a preliminary investigation for the development of an immunization schedule in a guinea pig model.a new candidate vector vaccine against human brucellosis based on recombinant influenza viral vectors (rivv) subtypes h5n1 expressing brucella outer membrane protein (omp) 16, l7/l12, omp19 or cu-zn sod proteins has been developed. this paper presents the results of the study of protection of the vaccine using on guinea pigs, including various options of administering, dose and frequency. provided data of the novel vaccine candidate will contribute to its further movement into the preclinical st ...202133593447
development of human vectored brucellosis vaccine formulation: assessment of safety and protectiveness of influenza viral vectors expressing brucella immunodominant proteins in mice and guinea pigs.in this paper, we first used recombinant influenza viral vector (rivv) subtype h5n1 expressing from the open reading frame of ns1 80 and ns1 124 amino acids of brucella outer membrane proteins (omp) 16 and 19, ribosomal l7/l12, and cu-zn superoxide dismutase (sod) proteins to develop a human brucellosis vaccine. we made 18 combinations of ivvs in mono-, bi-, and tetravalent vaccine formulations and tested them on mice to select the safest and most effective vaccine samples. then, the most effect ...202033274194
avidin-biotin recombinant nucleoprotein competitive elisa for the detection of peste des petits ruminants virus antibodies in sheep and goats.the present study describes the development of a truncated recombinant peste des petits ruminants virus (pprv) nucleoprotein (rpprv-npn) and its polyclonal antibodies-based immuno-diagnostic assay, avidin-biotin (ab) recombinant nucleoprotein competitive elisa (abrc-elisa) for the detection of pprv antibodies in the sheep and goats. the pprv n-terminal immunogenic region (1-266 aa) of nucleoprotein (npn) coding sequence was amplified and cloned into the petite vector. the rpprv-npn with a molecu ...202134119607
investigation of kluyveromyces marxianus as a novel host for large-scale production of porcine parvovirus virus-like particles.porcine parvovirus (ppv) is a parvovirinae virus that can cause embryonic and fetal loss and death and mummification in affected fetal pigs. unlike conventional vaccines, virus-like particles (vlps) inherit the natural structure of their authentic virions and highly immunostimulatory that can induce strong humoral immune and t cell responses with no risk of pathogenicity. the production of ppv vlps is still a challenge based on traditional expression platforms due to their low yields and high cu ...202133494762
characterization of antibodies in human immunoglobulin products from different regions worldwide.the antibody levels against a broad spectrum of pathogens were assessed in commercial intravenous immunoglobulin (ivig) manufactured from pooled plasma obtained from different global regions.202133524620
adjuvant effect of saponin in an oil-based monovalent (serotype o) foot-and-mouth disease virus vaccine on the antibody response in guinea pigs and cattle.to enhance the potency of a foot-and-mouth disease (fmd) vaccine, saponin was included in the vaccine formula. in this study, the combined effect of montanide isa 50 and saponin was evaluated. two experiments were performed in guinea pigs and one in cattle to determine the optimal antigen and saponin doses. only serotype o of foot-and-mouth disease virus (o/panasia-2 of me-sa topotype) was employed in preparation of the monovalent vaccine. all animals were immunized twice with a four-week interv ...202133871696
bi-functional gold nanocages enhance specific immunological responses of foot-and-mouth disease virus-like particles vaccine as a carrier and adjuvant.virus-like particle (vlp) vaccines have become one of the dominant vaccine candidates for foot-and-mouth disease (fmd). to further enhance the immunogenicity of vlp vaccines, gold nanocages (auncs) were selected as an adjuvant for the vaccine. our experiments demonstrated that auncs had little biotoxicity in vivo and in vitro and improved the uptake of vlp in bhk-21 and raw264.7 cell lines. the vlp-auncs activated dcs mainly through toll-like receptor 4 (tlr4) and promoted the secretion of il-6, ...202133484882
preclinical safety assessment of a combined vaccine against hepatitis a virus and enterovirus 71.since 2007, hepatitis a (hav) vaccination has been a part of the national immunization program of china. recognizing enterovirus 71 (ev71) as the most important pathogen in severe hand, foot and mouth disease, an inactivated ev71 vaccine was successfully marketed in 2015. based on the concept of one vaccine preventing two diseases and owing to similarities in vaccine preparation and the overlap of the eligible population, a combination of the inactivated hav vaccine and inactivated ev71 vaccine ...202134088510
humoral and cell-mediated immune responses to plant-produced african horse sickness virus vp7 quasi-crystals.african horse sickness (ahs) is a devastating viral disease affecting equines and has resulted in many disastrous epizootics. to date, no successful therapeutic treatment exists for ahs, and commercially used live-attenuated vaccines have various undesirable side effects. previous studies have shown that mice inoculated with insoluble african horse sickness virus (ahsv) vp7 crystals are protected from live challenge with a lethal dose of ahsv. this study investigates the humoral and cell-mediate ...202133421520
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