RESUMEN
BACKGROUND: Rabbit hemorrhagic disease (RHD) is an acute infectious disease that damages the rabbit industry by producing significant mortality rates in young and adult rabbits. RHD is better controlled by vaccination. OBJECTIVE: The current study's goal was to prepare and evaluate the immuno-enhancing effect of montanide ISA70 and aluminum hydroxide (Al(OH)3) gel incorporated within the inactivated RHDV2 vaccine and assess the vaccine's protective efficacy against the homologous and heterologous local RHDV2 strains in rabbits. METHODS: Inactivated RHDV vaccines were prepared using Montanide ISA70 oil or Al(OH)3 gel adjuvants and submitted to sterility, safety, and potency tests. 200 rabbits were equally divided into 4 groups: G1 (control), G2 (vaccinated with gel-incorporated vaccine), G3 (vaccinated with montanide-incorporated vaccine), and G4 (vaccinated with gel- and montanide-incorporated vaccines). Individual blood samples were collected from one week to six months from all groups. The vaccine's potency was measured by the HI test and protection percentage post challenge. RESULTS: Data revealed slightly increasing HI titer means reaching the 1st peak at 4 weeks post-vaccination (7.33, 7.67, and 7.33 log2 in the 2nd, 3rd, and 4th groups, respectively), then slightly decreasing and peaked again, giving 9.33 log2 for the2nd group at 3 months post-vaccination (MPV), 10.67 log2 for 3rd the group, and 10.33 log2 for the 4th group at 5 months post-vaccination. Titer gradually decreased but remained protective. The protection rate ranged from 80-100% and 80-90% for homologous and heterologous local RHDV2 vaccines, respectively, within 3 weeks and 6 months post-challenge. The montanide oil RHDV2 vaccine induced better protection than the aluminum gel RHDV2 vaccine. CONCLUSION: The results demonstrated evidence of cross-protection between RHDV2 strains. The oil emulsion vaccine induced higher and longer-lasting antibody titers than those obtained with the RHDV2 aluminum gel vaccine.
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Hidróxido de Aluminio , Infecciones por Caliciviridae , Virus de la Enfermedad Hemorrágica del Conejo , Vacunas Virales , Animales , Conejos , Hidróxido de Aluminio/farmacología , Hidróxido de Aluminio/administración & dosificación , Virus de la Enfermedad Hemorrágica del Conejo/inmunología , Vacunas Virales/inmunología , Infecciones por Caliciviridae/veterinaria , Infecciones por Caliciviridae/prevención & control , Geles , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Ácidos Oléicos/farmacología , Ácidos Oléicos/administración & dosificaciónRESUMEN
OBJECTIVES: Vaccinations should only be given to healthy cats, and deworming before vaccination is generally recommended; however, so far, no study has investigated the influence of intestinal parasitic infection on the immune response in kittens. The aim of this prospective study was to compare the antibody response to feline panleukopenia virus (FPV) vaccination in kittens with and without intestinal parasites. METHODS: Overall, 74 healthy kittens were included. Of these, 17 had intestinal parasites (12/17 Toxocara cati, 6/17 Cystoisospora felis, 1/17 Capillaria species). Both kittens with and without (n = 57) parasites received two primary kitten vaccinations with modified live FPV vaccines in a 4-week interval starting at the age of 8-12 weeks. Anti-FPV antibodies were determined at the beginning of the study (week 0) and at week 8 (4 weeks after the second vaccination) by haemagglutination inhibition. A ⩾four-fold titre increase (week 8 vs week 0) was defined as a response to vaccination. Comparison of the immune response in the kittens with and without intestinal parasites was performed using Pearson's χ2 test. RESULTS: Pre-vaccination antibodies were present in 4/17 (23.5%) kittens with intestinal parasites and in 24/57 (42.1%) without parasites. A ⩾four-fold titre increase was seen in 13/17 (76.5%) kittens with parasites compared with 32/57 (56.1%) kittens without parasites. There was neither a significant difference in pre-vaccination antibodies (P = 0.17), nor in vaccination response (P = 0.13) between kittens with and without parasites. CONCLUSIONS AND RELEVANCE: The results indicate that asymptomatic intestinal infections with endoparasites do not interfere with the immune response to kitten vaccination series. Parasitic infection (at least with T cati, C felis and Capillaria species) is therefore not a reason to postpone important vaccinations.
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Anticuerpos Antivirales , Virus de la Panleucopenia Felina , Panleucopenia Felina , Parasitosis Intestinales , Vacunas Virales , Animales , Gatos , Virus de la Panleucopenia Felina/inmunología , Panleucopenia Felina/prevención & control , Panleucopenia Felina/inmunología , Parasitosis Intestinales/veterinaria , Parasitosis Intestinales/prevención & control , Parasitosis Intestinales/inmunología , Anticuerpos Antivirales/sangre , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Masculino , Vacunación/veterinaria , Femenino , Enfermedades de los Gatos/prevención & control , Enfermedades de los Gatos/inmunología , Enfermedades de los Gatos/parasitología , Enfermedades de los Gatos/virología , Estudios Prospectivos , Infecciones por Caliciviridae/veterinaria , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/inmunologíaRESUMEN
Norovirus (NoV) infection is a major cause of gastroenteritis worldwide. The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity. To date, there are no approved NoV vaccines for clinical use. Here, we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector, AdC68, carrying the major capsid protein (VP1) of noroviral GI and GII genotypes. Compared to intramuscular (i.m.), intranasal (i.n.), or other prime-boost immunization regimens (i.m. â+ âi.m., i.m. â+ âi.n., i.n. â+ âi.m.), AdC68-GI.1-GII.3 (E1)-GII.4-GII.17 (E3), administered via i.n. â+ âi.n. induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid (BALF) and saliva against the four homologous VP1s in mice. It also significantly stimulated the production of blocking antibodies against the four genotypes. In response to re-stimulation with virus-like particles (VLP)-GI.1, VLP-GII.3, VLP-GII.4, and VLP-GII.17, the quadrivalent vaccine administered according to the i.n. â+ âi.n. regimen effectively triggered specific cell-mediated immune responses, primarily characterized by IFN-γ secretion. Furthermore, the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus to provide broad preventive immunity against the major GI/GII epidemic strains, making it a promising vaccine candidate for further development.
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Adenoviridae , Anticuerpos Antivirales , Infecciones por Caliciviridae , Vectores Genéticos , Ratones Endogámicos BALB C , Norovirus , Pan troglodytes , Vacunas Virales , Animales , Norovirus/inmunología , Norovirus/genética , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Ratones , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/inmunología , Vacunas Virales/inmunología , Vacunas Virales/genética , Vacunas Virales/administración & dosificación , Vectores Genéticos/genética , Vectores Genéticos/inmunología , Adenoviridae/genética , Adenoviridae/inmunología , Femenino , Proteínas de la Cápside/genética , Proteínas de la Cápside/inmunología , Inmunoglobulina G/sangre , Gastroenteritis/prevención & control , Gastroenteritis/virología , Gastroenteritis/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Inmunoglobulina A/sangre , Genotipo , Saliva/inmunología , Saliva/virología , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/virologíaRESUMEN
BACKGROUND: Norovirus gastroenteritis outbreaks were common in schools and kindergartens and were more related to faculty knowledge, attitude, and practice level. Gastroenteritis outbreaks caused by norovirus in educational institutions were the prominent cause of Public Health Emergency Events in China. This study aimed to explore the transformation in the contribution of KAP items related to outbreak prevention before and after intervention and the impact of demography factors on the intervention. METHODS: This study sampled 1095 kindergarten and 1028 school staff in Shenzhen, China. We created a questionnaire consisting of 35 items in 4 parts, and each item was rated on a scale of 1-5 according to the accuracy. Univariate analysis of non-parametric tests and binary logistic regression were used to estimate the score difference on demographic characteristics, each item and KAP. The odds ratios (OR) with 95% confidence and intervals (CI) for the association between statistical indicators were mainly used to explain the effects before and after intervention. RESULTS: Overall, 98.72% and 74.9% of the kindergarten and school participants were female, and all respondents had the highest scores difference of practice. Following intervention, univariate analysis indicated that primary school and female respondents achieved higher knowledge scores. Staff age beyond 35 (OR = 0.56, CI:0.34-0.92; OR = 0.67, CI:0.50-0.90) and with more than ten years of service (OR = 0.58, CI:0.36-0.91; OR = 0.38, CI:0.17-0.84) demonstrated a significantly lower post-intervention score for attitude and practice in both kindergartens and schools. The staff members exhibited a general lack of familiarity with the transmission of aerosols and the seasonal patterns of NoVs diarrhea pandemics. Item analysis revealed that kindergarten staff aged 26 and above demonstrated superior performance in terms of the efficacy of medical alcohol for inactivation (OR = 1.93, CI:1.13-3.31) and management strategies for unexplained vomiting among students (OR = 1.97, CI:1.21-3.18). Private school personnel displayed more significant improvement in their practices following educational interventions. School administrators' negative attitudes were primarily evident in their perspectives on morning inspections (OR = 0.11, CI:0.05-0.84). CONCLUSIONS: The potential negative impact of faculty age on NoVs-related knowledge can be mitigated by the positive attitudes fostered through seniority. Furthermore, it is imperative to urgently address the lack of knowledge among administrators, and the identification and treatment of vomiting symptoms should be emphasized as crucial aspects of school prevention strategies. Therefore, education authorities should implement comprehensive public health interventions in the future.
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Infecciones por Caliciviridae , Brotes de Enfermedades , Conocimientos, Actitudes y Práctica en Salud , Norovirus , Instituciones Académicas , Humanos , Femenino , Masculino , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/epidemiología , Adulto , China/epidemiología , Encuestas y Cuestionarios , Brotes de Enfermedades/prevención & control , Diarrea/prevención & control , Diarrea/epidemiología , Gastroenteritis/prevención & control , Gastroenteritis/epidemiología , Gastroenteritis/virología , Maestros/psicología , Maestros/estadística & datos numéricos , Persona de Mediana EdadRESUMEN
Dendritic cells (DCs) present an ideal target for delivering immunogenic cargo due to their potent antigen-presenting capabilities. This targeting approach holds promise in vaccine development by enhancing the efficiency of antigen recognition and capture by DCs. To identify a high-affinity targeting peptide binding to rabbit DCs, rabbit monocyte-derived DCs (raMoDCs) were isolated and cultured, and a novel peptide, HS (HSLRHDYGYPGH), was identified using a phage-displayed peptide library. Alongside HS, two other DC-targeting peptides, KC1 and MY, previously validated in our laboratory, were employed to construct recombinant Lactgobacillus reuteri fusion-expressed rabbit hemorrhagic disease virus (RHDV) capsid protein VP60. These recombinant Lactobacillus strains were named HS-VP60/L. reuteri, KC1-VP60/L. reuteri, and MY-VP60/L. reuteri. The ability of these recombinant Lactobacillus to bind rabbit DCs was evaluated both in vivo and in vitro. Results demonstrated that the DC-targeting peptide KC1 significantly enhanced the capture efficiency of recombinant Lactobacillus by raMoDCs, promoted DC maturation, and increased cytokine secretion. Furthermore, oral administration of KC1-VP60/L. reuteri effectively induced SIgA and IgG production in rabbits, prolonged rabbit survival post-challenge, and reduced RHDV copies in organs. In summary, the DC-targeting peptide KC1 exhibited robust binding to raMoDCs, and recombinant Lactobacillus expressing KC1-VP60 protein antigens efficiently induced systemic and mucosal immune responses in rabbits, conferring protective efficacy against RHDV. This study offers valuable insights for the development of novel RHDV vaccines.
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Células Dendríticas , Virus de la Enfermedad Hemorrágica del Conejo , Limosilactobacillus reuteri , Péptidos , Animales , Células Dendríticas/inmunología , Conejos , Virus de la Enfermedad Hemorrágica del Conejo/inmunología , Virus de la Enfermedad Hemorrágica del Conejo/genética , Limosilactobacillus reuteri/genética , Limosilactobacillus reuteri/inmunología , Péptidos/inmunología , Péptidos/genética , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/inmunología , Infecciones por Reoviridae/prevención & control , Infecciones por Reoviridae/inmunología , Proteínas de la Cápside/genética , Proteínas de la Cápside/inmunología , Vacunas Virales/inmunología , Vacunas Virales/genética , Lactobacillus/genética , Lactobacillus/inmunologíaRESUMEN
Background: The outbreak of norovirus represents a significant public health emergency within densely populated, impoverished, and underdeveloped areas and countries. Our objective is to conduct an epidemiology study of a norovirus outbreak that occurred in a kindergarten located in rural western China. We aim to raise awareness and garner increased attention towards the prevention and control of norovirus, particularly in economically underdeveloped regions. Methods: Retrospective on-site epidemiological investigation results, including data on school layout, case symptoms, onset time, disposal methods and sample testing results, questionnaire surveys, and case-control study were conducted in a kindergarten to analyze the underlying causes of the norovirus outbreak. Results: A total of 15 cases were identified, with an attack rate of 44.12% (15/34). Among them, 10 cases were diagnosed through laboratory tests, and 5 cases were diagnosed clinically. Vomiting (100%, 15/15) and diarrhea (93.33%, 14/15) were the most common symptoms in the outbreak. Case control study revealed that cases who had close contact (<1 m) with the patient's vomitus (OR = 5.500) and those who had close contact with similar patients (OR = 8.000) had significantly higher ORs compared to the control participants. The current study demonstrated that improper handling of vomitus is positively associated with norovirus outbreak. The absence of standardized disinfection protocols heightens the risk of norovirus outbreaks. Conclusion: To our knowledge, this study represents the first investigation into a norovirus outbreak in rural areas of western China. We aspire that amidst rapid economic development, a greater emphasis will be placed on the prevention and control of infectious diseases in economically underdeveloped areas and countries.
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Infecciones por Caliciviridae , Brotes de Enfermedades , Gastroenteritis , Norovirus , Población Rural , Humanos , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/prevención & control , Brotes de Enfermedades/prevención & control , Brotes de Enfermedades/estadística & datos numéricos , China/epidemiología , Femenino , Masculino , Estudios de Casos y Controles , Estudios Retrospectivos , Población Rural/estadística & datos numéricos , Gastroenteritis/epidemiología , Gastroenteritis/prevención & control , Gastroenteritis/virología , Gastroenteritis/economía , Preescolar , Encuestas y Cuestionarios , Instituciones Académicas , Niño , Países en Desarrollo/estadística & datos numéricosRESUMEN
Noroviruses are the second leading cause of death in children under the age of 5 years old. They are responsible for 200 million cases of diarrhoea and 50,000 deaths in children through the word, mainly in low-income countries. The objective of this review was to assess how the prevalence and genetic diversity of noroviruses have been affected by the introduction of rotavirus vaccines in Africa. PubMed, Web of Science and Science Direct databases were searched for articles. All included studies were conducted in Africa in children aged 0 to 5 years old with gastroenteritis. STATA version 16.0 software was used to perform the meta-analysis. The method of Dersimonian and Laird, based on the random effects model, was used for the statistical analyses in order to estimate the pooled prevalence's at a 95% confidence interval (CI). Heterogeneity was assessed by Cochran's Q test using the I2 index. The funnel plot was used to assess study publication bias. A total of 521 studies were retrieved from the databases, and 19 were included in the meta-analysis. The pooled norovirus prevalence's for pre- and post-vaccination rotavirus studies were 15% (95 CI, 15-18) and 13% (95 CI, 09-17) respectively. GII was the predominant genogroup, with prevalence of 87.64% and 91.20% respectively for the pre- and post-vaccination studies. GII.4 was the most frequently detected genotype, with rates of 66.84% and 51.24% respectively for the pre- and post-vaccination studies. This meta-analysis indicates that rotavirus vaccination has not resulted in a decrease in norovirus infections in Africa.
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Infecciones por Caliciviridae , Gastroenteritis , Variación Genética , Norovirus , Infecciones por Rotavirus , Vacunas contra Rotavirus , Humanos , Vacunas contra Rotavirus/inmunología , Vacunas contra Rotavirus/administración & dosificación , Lactante , África/epidemiología , Preescolar , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/virología , Norovirus/genética , Norovirus/clasificación , Norovirus/inmunología , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , Gastroenteritis/virología , Gastroenteritis/epidemiología , Gastroenteritis/prevención & control , Recién Nacido , Prevalencia , Rotavirus/genética , Rotavirus/inmunología , Rotavirus/clasificación , Vacunación/estadística & datos numéricosRESUMEN
Rabbit hemorrhagic disease virus 2 (RHDV2) emerged in the United States in 2018 and has spread in both domestic and wild rabbits nationwide. The virus has a high mortality rate and can spread rapidly once introduced in a rabbit population. Vaccination against RHDV2 provides the best protection against disease and should be considered by all rabbit owners. Here, we investigate the duration of immunity provided by vaccination with the Medgene Platform conditionally licensed commercial vaccine 6 months following the initial series. Rabbits received either the vaccination or a placebo and were challenged with RHDV2 6 months later. All vaccinated rabbits survived challenge whereas 18/19 non-vaccinated controls succumbed to infection within 10 or fewer days post-challenge. These results demonstrate lasting immunity following vaccination with the Medgene RHDV2 vaccine.
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Baculoviridae , Infecciones por Caliciviridae , Virus de la Enfermedad Hemorrágica del Conejo , Vacunación , Vacunas Sintéticas , Vacunas Virales , Animales , Virus de la Enfermedad Hemorrágica del Conejo/inmunología , Virus de la Enfermedad Hemorrágica del Conejo/genética , Conejos , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/inmunología , Infecciones por Caliciviridae/virología , Infecciones por Caliciviridae/veterinaria , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Vacunas Virales/genética , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Baculoviridae/genética , Baculoviridae/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunologíaRESUMEN
IMPORTANCE: Human norovirus (HuNoV) is highly infectious and can result in severe illnesses in the elderly and children. So far, there is no effective antiviral drug to treat HuNoV infection, and thus, the development of HuNoV vaccines is urgent. However, NoV evolves rapidly, and currently, at least 10 genogroups with numerous genotypes have been found. The genetic diversity of NoV and the lack of cross-protection between different genotypes pose challenges to the development of broadly protective vaccines. In this study, guided by structural alignment between GI.1 and GII.4 HuNoV VP1 proteins, several chimeric-type virus-like particles (VLPs) were designed through surface-exposed loop grafting. Mouse immunization studies show that two of the designed chimeric VLPs induced cross-immunity against both GI.1 and GII.4 HuNoVs. To our knowledge, this is the first designed chimeric VLPs that can induce cross-immune activities across different genogroups of HuNoV, which provides valuable strategies for the development of cross-reactive HuNoV vaccines.
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Infecciones por Caliciviridae , Epítopos , Genotipo , Norovirus , Vacunas Virales , Virión , Animales , Humanos , Ratones , Infecciones por Caliciviridae/inmunología , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/virología , Epítopos/química , Epítopos/genética , Epítopos/inmunología , Inmunización , Norovirus/química , Norovirus/clasificación , Norovirus/genética , Norovirus/inmunología , Vacunas Virales/química , Vacunas Virales/genética , Vacunas Virales/inmunología , Quimera/genética , Quimera/inmunología , Proteínas de la Cápside/química , Proteínas de la Cápside/genética , Proteínas de la Cápside/inmunología , Virión/química , Virión/genética , Virión/inmunologíaRESUMEN
Hypochlorous acid (HOCl), used as a liquid or a fog, has broad antimicrobial and deodorizing effects. Our facility was the first in Taiwan that was built with a system to supply stabilized, biosafe HOCl solution (50 ppm available chlorine concentration, pH 6) into a new animal barrier facility that housed genetically modified mice. The HOCl system creates an extremely clean environment that allows us to raise mice in static, filter-top cages and to handle them on open tables without the need for biologic safety cabinets (BSC). Our animal facility (AF) sometimes receives mice from outside sources that are infected with pathogens, notably murine norovirus (MNV), Helicobacter spp., and trichomonads. We found that our standard operation procedure (SOP) prevented cross-contamination to other mice, including those in adjacent cages. After the removal of infected mice from a room, the remaining mice remained uninfected, without the need for extensive environmental decontamination. Learning this allowed us to use a test-and-removal method to eliminate pathogens. In addition, infected mouse strains that were not commercially available were rederived by using cross-fostering. After finding unexpected infections, we were able to identify all infected mice by widespread screening. We then removed contaminated cages and performed cross-fostering as needed. This approach was able to successfully eliminate murine norovirus, Helicobacter spp., and trichomonads. Over the 12 y in which we managed this AF, we refined our husbandry methods and our approach to the detection and eradication of pathogens by using HOCl fog and solution, the test-and-removal, and cross-fostering.
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Infecciones por Caliciviridae , Norovirus , Animales , Ratones , Ácido Hipocloroso , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/veterinaria , Vivienda para Animales , Crianza de Animales Domésticos/métodosAsunto(s)
Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Humanos , Salud Pública , Brotes de Enfermedades/prevención & control , Gastroenteritis/epidemiología , Gastroenteritis/prevención & control , Reino Unido/epidemiología , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/prevención & controlRESUMEN
Noroviruses (NoVs) are one of the major causes of acute viral gastroenteritis in humans. Virus-like particles (VLPs) without genomes that mimic the capsid structure of viruses are promising vaccine candidates for the prevention of NoVs infection. To produce large amounts of recombinant protein, including VLPs, the silkworm-expression vector system (silkworm-BEVS) is an efficient and powerful tool. In this study, we constructed a recombinant baculovirus that expresses VP1 protein, the major structural protein of NoV GII.4. Expression analysis showed that the baculovirus-infected silkworm pupae expressed NoV VP1 protein more efficiently than silkworm larval fat bodies. We obtained about 4.9 mg of purified NoV VP1 protein from only five silkworm pupae. The purified VP1 protein was confirmed by dynamic light scattering and electron microscopy to form VLPs of approximately 40 nm in diameter. Antisera from mice immunized with the antigen blocked NoV VLPs binding to histo-blood group antigens of pig gastric mucin and also blocked NoV infection in intestinal epithelial cells derived from human induced pluripotent stem (iPS) cells. Our findings demonstrated that NoV VLP eliciting protective antibodies could be obtained in milligram quantities from a few silkworm pupae using the silkworm-BEVS.
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Partículas Similares a Virus Artificiales , Bombyx , Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Animales , Humanos , Ratones , Anticuerpos , Anticuerpos Antivirales , Bombyx/química , Bombyx/metabolismo , Infecciones por Caliciviridae/prevención & control , Proteínas de la Cápside/genética , Norovirus/genética , Norovirus/inmunología , Pupa , Porcinos , Partículas Similares a Virus Artificiales/inmunologíaRESUMEN
Norovirus (NoV) is an enteric non-enveloped virus which is the leading cause of gastroenteritis across all age groups. It is responsible for around 200,000 deaths annually and outbreaks are common in small communities such as educational and care facilities. 40% of all NoV outbreaks occur in long-term and acute-care facilities, forming the majority of outbreaks. Nosocomial settings set ideal environments for ease of transmission, especially due to the presence of immunocompromised groups. It is estimated to cost global economies around £48 billion a year, making it a global issue. NoV is transmitted via the faecal-oral route and infection with it results in asymptomatic cases or gastrointestinal disease. It has high mutational rates and this allows for new variants to emerge and be more resistant. The classification system available divides NoV into 10 genogroups and 49 genotypes based on whole amino acid sequencing of VP1 capsid protein and partial sequencing of RdRp, respectively. The most predominant genotypes which cause gastroenteritis in humans include GI.1 and GII.4, where GII.4 is responsible for more extreme clinical implications such as hospitalisation. In addition, GII.4 has been responsible for 6 pandemic strains, the last of which is the GII.4 Sydney (2012) variant. In recent years, the successful cultivation of HuNoV was reported in stem cell-derived human intestinal enteroids (HIEs), which promises to assist in giving a deeper understanding of its underlying mechanisms of infection and the development of more personalized control measures. There are no specific control measures against NoV, therefore common practices are used against it such as hand washing. No vaccine is available, but the HIL-214 candidate passed clinical phase 2b and shows promise.
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Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Humanos , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/prevención & control , Brotes de Enfermedades , Gastroenteritis/epidemiología , Gastroenteritis/prevención & control , Genotipo , Norovirus/genética , Filogenia , Ensayos Clínicos Fase II como AsuntoRESUMEN
OBJECTIVE: To evaluate efficacy of a novel vaccine against rabbit hemorrhagic disease virus 2 (RHDV2) in domestic rabbits. ANIMALS: 40 New Zealand White rabbits obtained from a commercial breeder. PROCEDURES: Rabbits were vaccinated and held at the production facility for the duration of the vaccination phase and transferred to Colorado State University for challenge with RHDV2. Rabbits were challenged with oral suspensions containing infectious virus and monitored for clinical disease for up to 10 days. Rabbits that died or were euthanized following infection were necropsied, and livers were evaluated for viral RNA via RT-PCR. RESULTS: None of the vaccinated animals (0/9) exhibited clinical disease or mortality following infection with RHDV2 while 9/13 (69%) of the control animals succumbed to lethal disease following infection. CLINICAL RELEVANCE: The novel vaccine described herein provided complete protection against lethal infection following RHDV2 challenge. Outside of emergency use, there are currently no licensed vaccines against RHDV2 on the market in the United States; as such, this vaccine candidate would provide an option for control of this disease now that RHDV2 has become established in North America.
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Infecciones por Caliciviridae , Virus de la Enfermedad Hemorrágica del Conejo , Vacunas , Conejos , Animales , Virus de la Enfermedad Hemorrágica del Conejo/genética , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/veterinaria , Vacunación/veterinariaRESUMEN
BACKGROUND: Human norovirus (HuNoV) is the leading viral cause of diarrhea, with GII.4 as the predominant genotype of HuNoV outbreaks globally. However, new genogroup variants emerge periodically, complicating the development of anti-HuNoV vaccines; other prophylactic or therapeutic medications specifically for HuNoV disease are lacking. Passive immunization using oral anti-HuNoV antibodies may be a rational alternative. Here, we explore the feasibility of using avian immunoglobulins (IgY) for preventing HuNoV infection in vitro in a human intestinal enteroid (HIE) model. METHODS: Hens were immunized with virus-like particles (VLP) of a GII.4 HuNoV strain (GII.4/CHDC2094/1974/US) by intramuscular injection. The resulting IgY was evaluated for inhibition of binding to histo-blood group antigens (HBGA) and viral neutralization against representative GII.4 and GII.6 clinical isolates, using an HIE model. RESULTS: IgY titers were detected by three weeks following initial immunization, persisting at levels of 1:221 (1:2,097,152) from 9 weeks to 23 weeks. Anti-HuNoV IgY significantly (p < 0.05) blocked VLP adhesion to HBGA up to 1:12,048 dilution (0.005 mg/mL), and significantly (p < 0.05) inhibited replication of HuNoV GII.4[P16] Sydney 2012 in HIEs up to 1:128 dilution (0.08 mg/mL). Neutralization was not detected against genotype GII.6. CONCLUSIONS: We demonstrate the feasibility of IgY for preventing infection of HIE by HuNoV GII.4. Clinical preparations should cover multiple circulating HuNoV genotypes for comprehensive effects. Plans for animal studies are underway.
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Antígenos de Grupos Sanguíneos , Infecciones por Caliciviridae , Norovirus , Humanos , Animales , Femenino , Pollos , Estudios de Factibilidad , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/veterinaria , Norovirus/genética , Antígenos de Grupos Sanguíneos/genética , AnticuerposRESUMEN
Rotavirus, a segmented double-stranded RNA virus of the Reoviridae family, is a primary cause of acute gastroenteritis in young children. In countries where rotavirus vaccines are widely used, norovirus (NoV) has emerged as the major cause of acute gastroenteritis. Towards the goal of creating a combined rotavirus-NoV vaccine, we explored the possibility of generating recombinant rotaviruses (rRVs) expressing all or portions of the NoV GII.4 VP1 capsid protein. This was accomplished by replacing the segment 7 NSP3 open reading frame with a cassette encoding, sequentially, NSP3, a 2A stop-restart translation element, and all or portions (P, P2) of NoV VP1. In addition to successfully recovering rRVs with modified SA11 segment 7 RNAs encoding NoV capsid proteins, analogous rRVs were recovered through modification of the segment 7 RNA of the RIX4414 vaccine strain. An immunoblot assay confirmed that rRVs expressed NoV capsid proteins as independent products. Moreover, VP1 expressed by rRVs underwent dimerization and was recognized by conformational-dependent anti-VP1 antibodies. Serially passaged rRVs that expressed the NoV P and P2 were genetically stable, retaining additional sequences of up to 1.1 kbp without change. However, serially passaged rRVs containing the longer 1.6-kb VP1 sequence were less stable and gave rise to virus populations with segment 7 RNAs lacking VP1 coding sequences. Together, these studies suggest that it may be possible to develop combined rotavirus-NoV vaccines using modified segment 7 RNA to express NoV P or P2. In contrast, development of potential rotavirus-NoV vaccines expressing NoV VP1 will need additional efforts to improve genetic stability. IMPORTANCE Rotavirus (RV) and norovirus (NoV) are the two most important causes of acute viral gastroenteritis (AGE) in infants and young children. While the incidence of RV AGE has been brought under control in many countries through the introduction of universal mass vaccination with live attenuated RV vaccines, similar highly effective NoV vaccines are not available. To pursue the development of a combined RV-NoV vaccine, we examined the potential of using RV as an expression vector of all or portions of the NoV capsid protein VP1. Our results showed that by replacing the NSP3 open reading frame in RV genome segment 7 RNA with a coding cassette for NSP3, a 2A stop-restart translation element, and VP1, recombinant RVs can be generated that express NoV capsid proteins. These findings raise the possibility of developing new generations of RV-based combination vaccines that provide protection against a second enteric pathogen, such as NoV.
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Proteínas de la Cápside , Gastroenteritis , Norovirus , Rotavirus , Vacunas Virales , Niño , Preescolar , Humanos , Proteínas de la Cápside/genética , Gastroenteritis/prevención & control , Gastroenteritis/virología , Norovirus/genética , ARN , Rotavirus/genética , Vacunas Combinadas , Infecciones por Rotavirus/prevención & control , Infecciones por Caliciviridae/prevención & controlRESUMEN
A birth cohort design was used to understand whether heterotypic ligand-blocking norovirus antibodies provide cross-protection within the GII genogroup. We found that almost one-half of children who experienced a norovirus GII episode had preexisting antibodies heterotypic to the infecting genotype; therefore, these antibodies did not provide cross-protection.
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Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Niño , Humanos , Lactante , Preescolar , Norovirus/genética , Infecciones por Caliciviridae/prevención & control , Gastroenteritis/prevención & control , Ligandos , Genotipo , HecesRESUMEN
BACKGROUND: Norovirus and sapovirus cause a large burden of acute gastroenteritis (AGE) in young children. We assessed protection conferred by norovirus and sapovirus AGE episodes against future episodes. METHODS: Between June 2017 and July 2018, we recruited 444 newborns in León, Nicaragua. Weekly household surveys identified AGE episodes over 36 months, and AGE stools were tested by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) for norovirus genogroup (G)I/GII and sapovirus. We used recurrent-event Cox models and negative control methods to estimate protection conferred by first episodes, controlling for observed and unobserved risk factors, respectively. RESULTS: Sapovirus episodes conferred a 69% reduced hazard of subsequent episodes using the negative control method. Norovirus GI (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.31, 1.3) and GII (HR = 0.20; 95% CI = 0.04, 0.44) episodes also appeared highly protective. Protection against norovirus GII was enhanced following two episodes. CONCLUSIONS: Evidence of natural immunity in early childhood provides optimism for the future success of pediatric norovirus and sapovirus vaccines.
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Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Sapovirus , Cohorte de Nacimiento , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/virología , Preescolar , Gastroenteritis/epidemiología , Gastroenteritis/prevención & control , Gastroenteritis/virología , Genotipo , Humanos , Lactante , Recién Nacido , Norovirus/genética , Sapovirus/genéticaRESUMEN
Feline calicivirus (FCV) is a common pathogen in domestic cats that is highly contagious, resistant to many disinfectants and demonstrates a high genetic variability. FCV infection can lead to serious or even fatal diseases. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of experts in feline medicine from 11 European countries, presents the current knowledge of FCV infection and fills gaps with expert opinions. FCV infections are particularly problematic in multicat environments. FCV-infected cats often show painful erosions in the mouth and mild upper respiratory disease and, particularly in kittens, even fatal pneumonia. However, infection can be associated with chronic gingivostomatitis. Rarely, highly virulent FCV variants can induce severe systemic disease with epizootic spread and high mortality. FCV can best be detected by reverse-transcriptase PCR. However, a negative result does not rule out FCV infection and healthy cats can test positive. All cats should be vaccinated against FCV (core vaccine); however, vaccination protects cats from disease but not from infection. Considering the high variability of FCV, changing to different vaccine strain(s) may be of benefit if disease occurs in fully vaccinated cats. Infection-induced immunity is not life-long and does not protect against all strains; therefore, vaccination of cats that have recovered from caliciviral disease is recommended.