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1.
Int J Infect Dis ; 105: 277-285, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33596479

RESUMO

OBJECTIVES: Rotavirus (RV) genotypes vary geographically, and this can affect vaccine effectiveness (VE). This study investigated the genotype distribution of RV and explored VE before introducing the RV vaccine to the national immunization programme in Vietnam. METHODS: This hospital-based surveillance study was conducted at Children's Hospital 1, Ho Chi Minh City in 2013-2018. Stool samples and relevant data, including vaccination history, were collected from children aged <5 years who were hospitalized with gastroenteritis. RV was detected using enzyme immunoassays and then genotyped. Children aged ≥6 months were included in the VE analysis. RESULTS: Overall, 5176 children were included in this study. RV was detected in 2421 children (46.8%). RV positivity decreased over the study period and was associated with age, seasonality, location and previous vaccination. Among 1105 RV-positive samples, G3P[8] was the most prevalent genotype (43.1%), followed by G8P[8] (19.7%), G1P[8] (12.9%) and G2P[4] (12.9%). Overall VE was 69.7% [95% confidence interval (CI) 53.3-80.6%] in fully vaccinated children and 58.6% (95% CI 44.1-69.4%) in children who had received at least one dose of RV vaccine. VE was highest for G3P[8] (95% CI 75.1-84.5%) and lowest for G2P[4] (95% CI 32.4-57.2%). CONCLUSIONS: RV remains a major cause of acute gastroenteritis requiring hospitalization in southern Vietnam. The RV vaccine is effective, but its effectiveness varies with RV genotype.


Assuntos
Genótipo , Vacinas contra Rotavirus/imunologia , Rotavirus/genética , Rotavirus/imunologia , Vacinação/estatística & dados numéricos , Criança , Pré-Escolar , Fezes/virologia , Feminino , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Hospitalização , Humanos , Lactente , Masculino , Avaliação de Resultados em Cuidados de Saúde , Rotavirus/fisiologia , Vietnã/epidemiologia
2.
Arch Virol ; 166(4): 995-1006, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33533975

RESUMO

Due to the lower efficacy of currently approved live attenuated rotavirus (RV) vaccines in developing countries, a new approach to the development of safe mucosally administered live bacterial vectors is being considered, using probiotic bacteria as an efficient delivery platform for heterologous RV antigens. Lactic acid bacteria (LAB), which are considered food-grade bacteria and normal microbiota, have been utilized throughout history as probiotics and developed since the 1990s as a delivery system for recombinant heterologous proteins. Over the last decade, LAB have frequently been used as a platform for the delivery of various RV antigens to the mucosa. Given the appropriate safety profile for neonates and providing the benefits of probiotics, recombinant LAB-based vaccines could potentially address the need for a subunit RV vaccine. The present review focuses mainly on different recombinant LAB vaccine constructs for RV and their potential as an alternative recombinant vaccine against RV disease.


Assuntos
Lactobacillales/metabolismo , Probióticos/administração & dosagem , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Rotavirus/imunologia , Animais , Antígenos Virais/genética , Antígenos Virais/metabolismo , Vetores Genéticos , Humanos , Lactobacillales/genética , Vacinas contra Rotavirus/efeitos adversos , Vacinas contra Rotavirus/genética , Anticorpos de Domínio Único/genética , Anticorpos de Domínio Único/metabolismo , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/metabolismo
3.
Nat Immunol ; 22(3): 381-390, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33589816

RESUMO

The integrin α4ß7 selectively regulates lymphocyte trafficking and adhesion in the gut and gut-associated lymphoid tissue (GALT). Here, we describe unexpected involvement of the tyrosine phosphatase Shp1 and the B cell lectin CD22 (Siglec-2) in the regulation of α4ß7 surface expression and gut immunity. Shp1 selectively inhibited ß7 endocytosis, enhancing surface α4ß7 display and lymphocyte homing to GALT. In B cells, CD22 associated in a sialic acid-dependent manner with integrin ß7 on the cell surface to target intracellular Shp1 to ß7. Shp1 restrained plasma membrane ß7 phosphorylation and inhibited ß7 endocytosis without affecting ß1 integrin. B cells with reduced Shp1 activity, lacking CD22 or expressing CD22 with mutated Shp1-binding or carbohydrate-binding domains displayed parallel reductions in surface α4ß7 and in homing to GALT. Consistent with the specialized role of α4ß7 in intestinal immunity, CD22 deficiency selectively inhibited intestinal antibody and pathogen responses.


Assuntos
Linfócitos B/enzimologia , Imunidade nas Mucosas , Cadeias beta de Integrinas/metabolismo , Integrinas/metabolismo , Mucosa Intestinal/enzimologia , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Animais , Linfócitos B/imunologia , Linfócitos B/virologia , Quimiotaxia de Leucócito , Modelos Animais de Doenças , Endocitose , Feminino , Cadeias beta de Integrinas/imunologia , Integrinas/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/virologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Proteína Tirosina Fosfatase não Receptora Tipo 6/deficiência , Proteína Tirosina Fosfatase não Receptora Tipo 6/genética , Rotavirus/imunologia , Rotavirus/patogenicidade , Infecções por Rotavirus/genética , Infecções por Rotavirus/imunologia , Infecções por Rotavirus/metabolismo , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/deficiência , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Transdução de Sinais , Técnicas de Cultura de Tecidos
4.
Artigo em Inglês | MEDLINE | ID: mdl-33573534

RESUMO

Abstract: This report, from the Australian Rotavirus Surveillance Program and collaborating laboratories Australia-wide, describes the rotavirus genotypes identified in children and adults with acute gastroenteritis during the period 1 January to 31 December 2018. During this period, 690 faecal specimens were referred for rotavirus G- and P- genotype analysis, including 607 samples that were confirmed as rotavirus positive. Of these, 457/607 were wild-type rotavirus strains and 150/607 were identified as rotavirus vaccine-like. Genotype analysis of the 457 wild-type rotavirus samples from both children and adults demonstrated that G3P[8] was the dominant genotype nationally, identified in 52% of samples, followed by G2P[4] (17%). The Australian National Immunisation Program, which previously included both RotaTeq and Rotarix vaccines, changed to Rotarix exclusively on 1 July 2017. Continuous surveillance is needed to identify if the change in vaccination schedule could affect rotavirus genotype distribution and diversity in Australia.


Assuntos
Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/imunologia , Austrália/epidemiologia , Pré-Escolar , Monitoramento Epidemiológico , Fezes/virologia , Feminino , Gastroenterite/epidemiologia , Gastroenterite/virologia , Genótipo , Humanos , Programas de Imunização , Lactente , Recém-Nascido , Masculino , Vigilância da População , Rotavirus/genética , Rotavirus/imunologia , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/administração & dosagem , Vacinas Atenuadas
5.
BMC Infect Dis ; 21(1): 18, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407207

RESUMO

BACKGROUND: Mozambique has a high burden of group A rotavirus (RVA) infection and chronic undernutrition. This study aimed to determine the frequency and potential risk factors for RVA infection in undernourished children under 5 years old with diarrhoea in Mozambique. METHODS: The analysis was conducted using data from March 2015 to December 2017, regarding children under 5 years old with at least one type of undernutrition. Anthropometric measures were used to calculate indices of weight-for-age, weight-for-height and height-for-age through the Z-Scores. RVA results were extracted from the National Diarrhoea Surveillance database. Descriptive statistics, chi-square test was used for qualitative variables and organized in contingency tables and 95% Confidence Intervals (CI) were considered for the calculation of RVA infection proportion and in the multiple logistic regression models to estimate the adjusted odds ratios (AOR). RESULTS: Of the 842 undernourished children included in the analysis, 27.2% (95% CI: 24.3-30.3%) were positive for RVA. The rate of RVA infection was 42.7% (95% CI: 38.0-47.5%) in the pre-vaccine period, with great reduction to 12.2% (95% CI: 9.4-15.6%) in the post-vaccine period. Most of the RVA undernourished children had severe wasting (33.3%) and severe stunting (32.0%). The risk of infection was significantly high in children from 0 to 11 months (p-value < 0.001) when compared to the age group of 24-59 months. A higher proportion of RVA infection was detected in households with five or more members (p-value = 0.029). Similar proportions of RVA were observed in children fed only by breast milk (34.9%) and breast milk with formula (35.6%). A higher proportion of undernourished HIV-positive children co-infected with RVA (7.4%) was observed. CONCLUSIONS: The frequency of RVA infection in undernourished children declined following the introduction of the vaccine in Mozambique. Beyond the temporal variation, Maputo province, age and crowded households were also associated to RVA infection. A high proportion of RVA infection was observed in children with severe wasting and a triple burden of disease: undernutrition, RVA and HIV, highlighting the need to conduct follow-up studies to understand the long-term impact of these conditions on children's development.


Assuntos
Transtornos da Nutrição Infantil/epidemiologia , Diarreia/epidemiologia , Desnutrição/epidemiologia , Infecções por Rotavirus/epidemiologia , Rotavirus/imunologia , Animais , Aleitamento Materno , Pré-Escolar , Comorbidade , Estudos Transversais , Diarreia/virologia , Características da Família , Fezes/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Moçambique/epidemiologia , Prevalência , Fatores de Risco , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/uso terapêutico
6.
Viruses ; 13(1)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33419150

RESUMO

Rotavirus causes severe gastroenteritis in children. Although vaccines are implemented, rotavirus-related diarrhea still claims ~200,000 lives annually worldwide, mainly in low-income settings, pointing to a need for improved vaccine tactics. To meet such a public health need, a P24-VP8* nanoparticle displaying the glycan-binding VP8* domains, the major neutralizing antigens of rotavirus, was generated as a new type of rotavirus vaccine. We reported here our development of a P24-VP8* nanoparticle-based trivalent vaccine. First, we established a method to produce tag-free P24-VP8* nanoparticles presenting the VP8*s of P[8], P[4], and P[6] rotaviruses, respectively, which are the three predominantly circulating rotavirus P types globally. This approach consists of a chemical-based protein precipitation and an ion exchange purification, which may be scaled up for large vaccine production. All three P24-VP8* nanoparticle types self-assembled efficiently with authentic VP8*-glycan receptor binding function. After they were mixed as a trivalent vaccine, we showed that intramuscular immunization of the vaccine elicited high IgG titers specific to the three homologous VP8* types in mice. The resulted mouse sera strongly neutralized replication of all three rotavirus P types in cell culture. Thus, the trivalent P24-VP8* nanoparticles are a promising vaccine candidate for parenteral use against multiple P types of predominant rotaviruses.


Assuntos
Polissacarídeos/imunologia , Proteínas de Ligação a RNA/imunologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/uso terapêutico , Proteínas não Estruturais Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Polissacarídeos/genética , Proteínas de Ligação a RNA/genética , Rotavirus/imunologia , Proteínas não Estruturais Virais/genética
8.
Methods Mol Biol ; 2183: 119-182, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32959244

RESUMO

Chromatography is a widely used method in the biotechnology industry and functions to separate the desired product from process and product related impurities. There is a multitude of resins available based on different modalities (such as charge, hydrophobicity, and affinity) to provide a spectrum of approaches to meet the separation challenges of the diverse products. The challenge of developing viral antigen purification processes is addressed in this method. A unique feature of this product class is that in order to protect against more than one strain of an antigen, vaccines are often multivalent. This entails multiple production processes for each antigen, all of which will require separate development and validation. Ideally, a universal purification method is sought, but differences in the protein subunits (frequently used as the antigens) make this challenging and often-bespoke purification steps are required. This means process development for the chromatographic stages of these products can be particularly challenging and labour intensive. With the numerous choices available, making critical process decisions that are usually unique to each product, process, and strain, can be costly and time-consuming. To address this, scale down purification at <1.0 mL column volume and automation approaches are increasingly applied to increase throughput. In this work, a method is described wherein a Tecan Freedom EVO® automated liquid handler is deployed for the evaluation of different resin chemistries and buffer conditions to find a suitable purification strategy. This method allows for the rapid evaluation of the separation viral antigens where limited information on chromatography behavior is known at the early stages of process development. Here, we demonstrate the methodology firstly by explaining the automated purification script and secondly by applying the script for an efficient purification development for different serotypes of rotavirus antigens.


Assuntos
Antígenos Virais/isolamento & purificação , Cromatografia/métodos , Ensaios de Triagem em Larga Escala , Automação Laboratorial , Técnicas de Cultura de Células , Rotavirus/imunologia , Fluxo de Trabalho
9.
BMC Infect Dis ; 20(1): 740, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036575

RESUMO

BACKGROUND: From 2016, the Government of India introduced the oral rotavirus vaccine into the national immunization schedule. Currently, two indigenously developed vaccines (ROTAVAC, Bharat Biotech; ROTASIIL, Serum Institute of India) are included in the Indian immunization program. We report the rotavirus disease burden and the diversity of rotavirus genotypes from 2005 to 2016 in a multi-centric surveillance study before the introduction of vaccines. METHODS: A total of 29,561 stool samples collected from 2005 to 2016 (7 sites during 2005-2009, 3 sites from 2009 to 2012, and 28 sites during 2012-2016) were included in the analysis. Stools were tested for rotavirus antigen using enzyme immunoassay (EIA). Genotyping was performed on 65.8% of the EIA positive samples using reverse transcription- polymerase chain reaction (RT-PCR) to identify the G (VP7) and P (VP4) types. Multinomial logistic regression was used to quantify the odds of detecting genotypes across the surveillance period and in particular age groups. RESULTS: Of the 29,561 samples tested, 10,959 (37.1%) were positive for rotavirus. There was a peak in rotavirus positivity during December to February across all sites. Of the 7215 genotyped samples, G1P[8] (38.7%) was the most common, followed by G2P[4] (12.3%), G9P[4] (5.8%), G12P[6] (4.2%), G9P[8] (4%), and G12P[8] (2.4%). Globally, G9P[4] and G12P[6] are less common genotypes, although these genotypes have been reported from India and few other countries. There was a variation in the geographic and temporal distribution of genotypes, and the emergence or re-emergence of new genotypes such as G3P[8] was seen. Over the surveillance period, there was a decline in the proportion of G2P[4], and an increase in the proportion of G9P[4]. A higher proportion of mixed and partially typed/untyped samples was also seen more in the age group 0-11 months. CONCLUSIONS: This 11 years surveillance highlights the high burden of severe rotavirus gastroenteritis in Indian children < 5 years of age before inclusion of rotavirus vaccines in the national programme. Regional variations in rotavirus epidemiology were seen, including the emergence of G3P[8] in the latter part of the surveillance. Having pre-introduction data is important to track changing epidemiology of rotaviruses, particularly following vaccine introduction.


Assuntos
Gastroenterite/epidemiologia , Genótipo , Hospitalização , Infecções por Rotavirus/epidemiologia , Rotavirus/genética , Doença Aguda , Antígenos Virais/imunologia , Pré-Escolar , Fezes/virologia , Feminino , Gastroenterite/prevenção & controle , Gastroenterite/virologia , Técnicas de Genotipagem , Humanos , Programas de Imunização , Esquemas de Imunização , Técnicas Imunoenzimáticas , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotavirus/imunologia , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/imunologia
10.
BMC Infect Dis ; 20(1): 656, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894071

RESUMO

BACKGROUND: Several studies have shown a substantial impact of Rotavirus (RV) vaccination on the burden of RV and all-cause acute gastroenteritis (AGE). However, the results of most impact studies could be confused by a dynamic and complex space-time process. Therefore, there is a need to analyse the impact of RV vaccination on RV and AGE hospitalisations in a space-time framework to detect geographical-time patterns while avoiding the potential confusion caused by population inequalities in the impact estimations. METHODS: A retrospective population-based study using real-world data from the Valencia Region was performed among children aged less than 3 years old in the period 2005-2016. A Bayesian spatio-temporal model was constructed to analyse RV and AGE hospitalisations and to estimate the vaccination impact measured in averted hospitalisations. RESULTS: We found important spatio-temporal patterns in RV and AGE hospitalisations, RV vaccination coverage and in their associated adverted hospitalisations. Overall, ~ 1866 hospital admissions for RV were averted by RV vaccination during 2007-2016. Despite the low-medium vaccine coverage (~ 50%) in 2015-2016, relevant 36 and 20% reductions were estimated in RV and AGE hospitalisations respectively. CONCLUSIONS: The introduction of the RV vaccines has substantially reduced the number of RV hospitalisations, averting ~ 1866 admissions during 2007-2016 which were space and time dependent. This study improves the methodologies commonly used to estimate the RV vaccine impact and their interpretation.


Assuntos
Gastroenterite/epidemiologia , Hospitalização , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/economia , Rotavirus/imunologia , Vacinação , Doença Aguda , Teorema de Bayes , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Vacinas contra Rotavirus/imunologia , Fatores Socioeconômicos , Espanha/epidemiologia , Fatores de Tempo , Cobertura Vacinal
11.
BMC Infect Dis ; 20(1): 712, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993511

RESUMO

BACKGROUND: Japan's National Immunization Program does not cover rotavirus vaccine and no government subsidies are available. This study aimed to measure the uptake of and determinants that influenced self-paid rotavirus vaccination, including socioeconomic status and relative poverty. METHODS: We conducted a cross-sectional study at health check-ups for all children aged 18 months in Kanazawa, Japan, between December 2017 and July 2018. Community nurses collected information on self-paid vaccination history, parents' perceptions of and recommendations for rotavirus vaccine, and socioeconomic status in interviews using a unified questionnaire. We used multivariable logistic regression to assess vaccine uptake and possible determinants. RESULTS: In total, 1282 participants were enrolled. The estimated rotavirus vaccine coverage was 72.9%. Perceptions that rotavirus gastroenteritis was serious and that the rotavirus vaccine was effective, pediatricians' recommendations, information from the city office, magazine and Internet articles, and higher parental education level were associated with higher rotavirus vaccine uptake. Lower household income was associated with decreased rotavirus vaccine uptake. Vaccine expense, fear of adverse reactions to the vaccine, number of household members and siblings, and children's characteristics were not correlated with rotavirus vaccination. Poverty was associated with decreased rotavirus vaccine uptake, even after adjustment for other determinants (adjusted odds ratio 0.49, 95% confidence interval: 0.26-0.90). CONCLUSION: Parents' perceptions, socioeconomic status, relative poverty, and pediatricians' recommendations are determinants of vaccination. This study suggests that appropriate information about rotavirus vaccine, subsidies for those of lower socioeconomic status, and national recommendations are necessary to achieve higher coverage.


Assuntos
Pais/psicologia , Percepção , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/economia , Rotavirus/imunologia , Classe Social , Vacinação/economia , Adulto , Estudos Transversais , Feminino , Humanos , Programas de Imunização , Renda , Lactente , Japão/epidemiologia , Modelos Logísticos , Masculino , Razão de Chances , Pobreza , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/imunologia , Inquéritos e Questionários
12.
Ann Afr Med ; 19(3): 198-202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32820733

RESUMO

Background: Rotavirus remains one of the main causative agents of gastroenteritis in young children. This happens, especially in countries (e.g., Nigeria) that have not yet introduced the vaccine into the national immunization program. A significant prevalence of Rotavirus infection both in children and adults without major symptoms has earlier been reported. This study aimed at defining the prevalence of asymptomatic Rotavirus infection from apparently healthy children in Maiduguri, Borno State, Northeastern Nigeria. Methods: A total of 269 stool samples were randomly collected from apparently healthy children <15 years of age from July 2017 to June 2018. All samples were screened using a commercially available enzyme-linked immunosorbent assay kit for the presence of Rotavirus antigen. The Rotavirus-positive samples were further subjected to polyacrylamide gel electrophoresis (PAGE) to determine their RNA electropherotypes. Results: A total of 59 stool samples (19.9%) were Rotavirus positive with peaks observed in the cold dry season, among male children, and 6-10 years of age group. A total of 50 randomly selected Rotavirus-positive samples were subjected to PAGE, and none of the samples showed either long or short profiles. Conclusion: This study shows that Rotavirus can be shed into environments without any signs and symptoms. In view of this, the Rotavirus vaccine should be considered a priority and be introduced in the existing national immunization program in Nigeria, particularly in Borno State.


Assuntos
Infecções Assintomáticas/epidemiologia , Fezes/virologia , Gastroenterite/epidemiologia , Infecções por Rotavirus/epidemiologia , Rotavirus/isolamento & purificação , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Gastroenterite/virologia , Genótipo , Humanos , Masculino , Nigéria/epidemiologia , Prevalência , Rotavirus/genética , Rotavirus/imunologia , Infecções por Rotavirus/virologia
13.
BMC Infect Dis ; 20(1): 596, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787859

RESUMO

BACKGROUND: Group A Rotavirus (RVA), despite being an important pathogen in hospitalized children, is less studied in pediatric outpatients, and even rarely investigated in adults. This study aims to understand the genetic diversity of RVA in outpatients across all age groups in Shanghai, and thus providing a molecular basis for vaccine implementation and evaluation. METHODS: Stool samples were first screened by Real-time Reverse Transcription Polymerase Chain Reaction (rRT-PCR). RVA genotyping was performed through the amplification of partial VP7 and VP4 gene. Strains of interest were further sequenced and analyzed using MEGA 6.0. RESULTS: Four thousand nine hundred one samples were collected, from which 7.61% (373 cases) were screened positive for RVA. RVA prevalence was higher in children (9.30%) than in adults (7.21%) (χ2 = 4.72, P < 0.05). 9.38% RVA positive cases had taken antibiotics before hospital visit while 49.60% had been prescribed antibiotics afterwards. RVA displayed a strong seasonality in both adults and children with a shared commonality in genotype repertoire, where G9P[8] was the most prevalent strain (67.96%) followed by G3P[8] (15.49%) and G1P[8] (12.32%). Meanwhile the first local case of fecal shedding of the G10P[15] vaccine strain was also discovered. CONCLUSIONS: While the prevalence of rotavirus is highest during cold seasons, it is revealed for the first time that G9P[8] is the predominant genotype in both adults and pediatric outpatients. Clinically, higher occurrence of nausea or vomiting was observed in RVA positive cases. Antibiotic overuse was implicated in both non-clinical and clinical settings. The finding emphasizes the importance of RVA genotyping in surveillance as it provides the basis for new vaccine application as well as a baseline for future vaccine efficacy evaluation.


Assuntos
Assistência Ambulatorial/métodos , Gastroenterite/epidemiologia , Gastroenterite/virologia , Variação Genética , Infecções por Rotavirus/epidemiologia , Rotavirus/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China/epidemiologia , Fezes/virologia , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotavirus/imunologia , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/imunologia , Estações do Ano , Adulto Jovem
14.
J Virol ; 94(18)2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32759316

RESUMO

An entirely plasmid-based reverse genetics (RG) system was recently developed for rotavirus (RV), opening new avenues for in-depth molecular dissection of RV biology, immunology, and pathogenesis. Several improvements to further optimize the RG efficiency have now been described. However, only a small number of individual RV strains have been recovered to date. None of the current methods have supported the recovery of murine RV, impeding the study of RV replication and pathogenesis in an in vivo suckling mouse model. Here, we describe useful modifications to the RG system that significantly improve rescue efficiency of multiple RV strains. In addition to the 11 group A RV segment-specific (+)RNAs [(+)ssRNAs], a chimeric plasmid was transfected, from which the capping enzyme NP868R of African swine fever virus (ASFV) and the T7 RNA polymerase were expressed. Second, a genetically modified MA104 cell line was used in which several components of the innate immunity were degraded. Using this RG system, we successfully recovered the simian RV RRV strain, the human RV CDC-9 strain, a reassortant between murine RV D6/2 and simian RV SA11 strains, and several reassortants and reporter RVs. All these recombinant RVs were rescued at a high efficiency (≥80% success rate) and could not be reliably rescued using several recently published RG strategies (<20%). This improved system represents an important tool and great potential for the rescue of other hard-to-recover RV strains such as low-replicating attenuated vaccine candidates or low-cell culture passage clinical isolates from humans or animals.IMPORTANCE Group A rotavirus (RV) remains as the single most important cause of severe acute gastroenteritis among infants and young children worldwide. An entirely plasmid-based reverse genetics (RG) system was recently developed, opening new ways for in-depth molecular study of RV. Despite several improvements to further optimize the RG efficiency, it has been reported that current strategies do not enable the rescue of all cultivatable RV strains. Here, we described a helpful modification to the current strategies and established a tractable RG system for the rescue of the simian RRV strain, the human CDC-9 strain, and a murine-like RV strain, which is suitable for both in vitro and in vivo studies. This improved RV reverse genetics system will facilitate study of RV biology in both in vitro and in vivo systems that will facilitate the improved design of RV vaccines, better antiviral therapies, and expression vectors.


Assuntos
Regulação Viral da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Vírus Reordenados/genética , Genética Reversa/métodos , Rotavirus/genética , Proteínas Virais/genética , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/imunologia , Animais , Chlorocebus aethiops , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Fatores Reguladores de Interferon/deficiência , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/imunologia , Camundongos , Nucleotidiltransferases/genética , Nucleotidiltransferases/imunologia , Plasmídeos/química , Plasmídeos/metabolismo , Capuzes de RNA , Vírus Reordenados/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Rotavirus/imunologia , Fator de Transcrição STAT1/deficiência , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/imunologia , Transfecção , Células Vero , Proteínas Virais/imunologia , Replicação Viral
16.
BMC Infect Dis ; 20(1): 504, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660437

RESUMO

BACKGROUND: Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010-June 2014) and post- (July 2014-December 2018) RVA vaccine introduction. METHODS: Stool samples were collected from children aged < 13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic Nairobi, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged < 5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and VP7 and VP4 genes sequenced to infer genotypes. RESULTS: We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P [8] (45.8%), G8P [4] (15.8%), G9P [8] (13.2%), G2P [4] (7.0%) and G3P [6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P [8] (52.1%), G2P [4] (20.7%) and G3P [8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of vaccine heterotypic genotypes, such as the commonly DS-1-like G2P [4] (7.0 to 20.7%, P < .001) and G3P [8] (1.3 to 16.1%, P < .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P [4] (15.8 to 0.4%, P < .001) and G9P [8] (13.2 to 5.4%, P < .001) in the post-vaccine introduction period. Phylogenetic analysis of genotype G1P [8], revealed circulation of strains of lineages G1-I, G1-II and P [8]-1, P [8]-III and P [8]-IV. Considerable genetic diversity was observed between the pre and post-vaccine strains, evidenced by distinct clusters. CONCLUSION: Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity.


Assuntos
Genótipo , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/uso terapêutico , Rotavirus/genética , Rotavirus/imunologia , Vacinação , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Fezes/virologia , Feminino , Gastroenterite/etiologia , Humanos , Esquemas de Imunização , Lactente , Quênia/epidemiologia , Masculino , Filogenia , Prevalência , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/efeitos adversos , Vacinas contra Rotavirus/imunologia , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico
17.
J Biomed Sci ; 27(1): 66, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32438911

RESUMO

BACKGROUND: Rotaviruses (RVs) are recognized as a major cause of acute gastroenteritis (AGE) in infants and young children worldwide. Here we summarize the virology, disease burden, prevalence, distribution of genotypes and seasonality of RVs, and the current status of RV vaccination in Southeast Asia (Cambodia, Indonesia, Lao People's Democratic Republic, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam) from 2008 to 2018. METHODS: Rotavirus infection in Children in Southeast Asia countries was assessed using data from Pubmed and Google Scholars. Most countries in Southeast Asia have not yet introduced national RV vaccination programs. We exclude Brunei Darussalam, and Timor Leste because there were no eligible studies identified during that time. RESULTS: According to the 2008-2018 RV surveillance data for Southeast Asia, 40.78% of all diarrheal disease in children were caused by RV infection, which is still a major cause of morbidity and mortality in children under 5 years old in Southeast Asia. Mortality was inversely related to socioeconomic status. The most predominant genotype distribution of RV changed from G1P[8] and G2P[4] into the rare and unusual genotypes G3P[8], G8P[8], and G9P[8]. Although the predominat strain has changed, but the seasonality of RV infection remains unchanged. One of the best strategies for decreasing the global burden of the disease is the development and implementation of effective vaccines. CONCLUSIONS: The most predominant genotype distribution of RV was changed time by time. Rotavirus vaccine is highly cost effective in Southeast Asian countries because the ratio between cost per disability-adjusted life years (DALY) averted and gross domestic product (GDP) per capita is less than one. These data are important for healthcare practitioners and officials to make appropriate policies and recommendations about RV vaccination.


Assuntos
Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Ásia Sudeste , Pré-Escolar , Humanos , Lactente , Rotavirus/genética , Rotavirus/imunologia , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/imunologia
18.
Mol Biol (Mosk) ; 54(2): 278-284, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32392197

RESUMO

Thanks to their strong immunostimulating properties and safety for humans, plant viruses represent an appropriate basis for the design of novel vaccines. The coat protein of Alternanthera mosaic virus can form virus-like particles that are stable under physiological conditions and have adjuvant properties. This work presents a recombinant human rotavirus A antigen based on the epitope of rotavirus structural protein VP6, using Alternanthera mosaic virus coat protein as a carrier. An expression vector containing the gene of Alternanthera mosaic virus (MU strain) coat protein fused to the epitope of rotavirus protein VP6 was designed. Immunoblot analysis showed that the chimeric protein was effectively recognized by commercial polyclonal antibodies to rotavirus and therefore is a suitable candidate for development of a vaccine prototype. Interaction of the chimeric recombinant protein with the native coat protein of Alternanthera mosaic virus and its RNA resulted in the formation of ribonucleoprotein complexes that were recognized by anti-rotavirus antibodies.


Assuntos
Antígenos Virais/imunologia , Proteínas do Capsídeo/imunologia , Potexvirus/imunologia , Rotavirus/imunologia , Anticorpos Antivirais , Humanos , Proteínas Recombinantes/imunologia
19.
PLoS One ; 15(5): e0232941, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469927

RESUMO

Child mortality from rotavirus gastroenteritis remains high in Nigeria, representing 14% of all rotavirus deaths worldwide. Here, we examine the potential impact and cost-effectiveness of national rotavirus vaccine introduction in geographic and economic subpopulations of Nigeria. We projected the health and economic outcomes of rotavirus vaccination in children over the first five years of life using a spreadsheet-based model. We modeled child populations using national survey data on rotavirus mortality risk factors and vaccination coverage to predict burden and impact across regional and wealth quintile subpopulations within Nigeria. Our base case considered introduction of a general rotavirus vaccine, modeled to encompass characteristics of existing vaccines, versus no vaccine. Base case costs were estimated from the government perspective, assuming Gavi subsidies, over the first five years. We also present estimates from the cost of vaccination from the perspective of Gavi. We explored uncertainty in model parameters through probabilistic uncertainty, one-way sensitivity, and scenario analyses. According to our estimates, rotavirus enteritis was responsible for 47,898 [95% Uncertainty Limits: 35,361; 63,703] child deaths per year, with approximately 80% of the national burden concentrated in the three northern regions of Nigeria. Rotavirus vaccination was estimated to prevent 6,454 [3,960; 9,721] deaths, 13% [9%; 18%] of the national annual RV burden. National ICERs for rotavirus vaccination from the Nigerian government and Gavi perspectives were US$47 [$18; $105] and $62 [$29; $130] per DALY averted, respectively. General rotavirus vaccination was projected to reduce rotavirus mortality by only 6% [4%; 9%] in the North West region compared to 35% [24%; 47%] in the South East region. Base case ICERs ranged from US$25 [10; 56] per DALY averted in North West to US$64 [18; 157] per DALY averted in South South. Gavi perspective ICERs ranged from US$33 [$15; $68] in North West to US$88 [35; 191] per DALY averted in South South. According to one-way sensitivity analyses, ICERs were most sensitive to vaccine efficacy, followed by estimated administrative costs and rotavirus mortality. Disparities in mortality reduction were largely driven by inequality in vaccination coverage across regions and between socioeconomic subpopulations. Due to high, persistent, and inequitable burden of rotavirus in Nigeria, routine vaccination with any of these rotavirus vaccines would be an high impact and cost-effective strategy in reducing child mortality.


Assuntos
Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/economia , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Diarreia/virologia , Feminino , Política de Saúde , Humanos , Programas de Imunização/economia , Lactente , Masculino , Modelos Teóricos , Nigéria/epidemiologia , Fatores de Risco , Rotavirus/imunologia , Rotavirus/patogenicidade , Infecções por Rotavirus/economia , Infecções por Rotavirus/mortalidade , Vacinas contra Rotavirus/imunologia , Vacinação/economia , Cobertura Vacinal
20.
Sci Rep ; 10(1): 7165, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32346042

RESUMO

Perinatal hepatic inflammation can have devastating consequences. Monocytes play an important role in the initiation and resolution of inflammation, and their diverse functions can be attributed to specific cellular subsets: pro-inflammatory or classical monocytes (Ly6cHi) and pro-reparative or non-classical monocytes (Ly6cLo). We hypothesized that inherent differences in Ly6cHi classical monocytes and Ly6cLo non-classical monocytes determine susceptibility to perinatal hepatic inflammation in late gestation fetuses and neonates. We found an anti-inflammatory transcriptional profile expressed by Ly6cLo non-classical monocytes, and a physiologic abundance of these cells in the late gestation fetal liver. Unlike neonatal pups, late gestation fetuses proved to be resistant to rhesus rotavirus (RRV) mediated liver inflammation. Furthermore, neonatal pups were rendered resistant to RRV-mediated liver injury when Ly6cLo non-classical monocytes were expanded. Pharmacologic inhibition of Ly6cLo non-classical monocytes in this setting restored susceptibility to RRV-mediated disease. These data demonstrate that Ly6cLo monocytes promote resolution of perinatal liver inflammation in the late gestation fetus, where there is a physiologic expansion of non-classical monocytes, and in the neonatal liver upon experimental expansion of these cells. Therapeutic strategies directed towards enhancing Ly6cLo non-classical monocyte function may mitigate the detrimental effects of perinatal liver inflammation.


Assuntos
Antígenos Ly/imunologia , Hepatite Animal/imunologia , Monócitos/imunologia , Infecções por Rotavirus/imunologia , Rotavirus/imunologia , Animais , Hepatite Animal/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Monócitos/patologia , Infecções por Rotavirus/patologia
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