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The Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) is the World Health Organization's key standing advisory body to conduct an independent review of research, particularly of transmission and economic modeling analyses that estimate the impact and value of vaccines. From 26th February-1st March 2024, at its first of two semi-annual meetings, IVIR-AC provided feedback and recommendations across four sessions; this report summarizes the proceedings and recommendations from that meeting. Session topics included modeling of the impact and cost-effectiveness of the R21/Matrix-M malaria vaccine, meta-analysis of economic evaluations of vaccines, a global analysis estimating the impact of vaccination over the last 50 years, and modeling the impact of different RTS,S malaria vaccine dose schedules in seasonal settings.
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Comités Consultivos , Vacunas contra la Malaria , Organización Mundial de la Salud , Humanos , Vacunas contra la Malaria/administración & dosificación , Vacunas contra la Malaria/inmunología , Análisis Costo-Beneficio , Vacunación/métodos , Malaria/prevención & control , Inmunización/métodosRESUMEN
Acute gastroenteritis (AGE) caused by rotavirus (RV) remains a public health issue in China. To accelerate the mass rotavirus vaccination, it is important to inform the policy maker, and the public of the economic burden caused by rotavirus infection. A meta-analysis was conducted applying standardized algorithms. Articles published before January 1, 2023, in English and Chinese were searched through PubMed, CNKI, and WanFang Data. Studies with cost analysis of RV AGE were included. A random-effects model was applied to synthesize the total cost of RV AGE from the societal perspective. A prospective survey aimed to measure the cost of RV AGE was conducted in 2021 and 2022 in Shaoxing city, Zhejiang province, that can represent the developed region. The cost data was applied as deviation indicator, in comparison with the pooled estimate generated from meta-analysis. Totally 286 articles were identified, and eventually 12 studies were included. The pooled total social cost of RV AGE was US$282.1 (95%CI: US$213.4-350.7). The pooled private cost of RV AGE was US$206.4 (95%CI: US$155.2-257.5). RV AGE hospitalized and RV AGE incurred in developed regions caused remarkable higher burden (US$631.2 [95%CI: US$512.6-749.8], and US$333.6 [95%CI: US$234.1-433.2] respectively), compared to RV AGE treated at outpatient, and incurred in less developed regions. Our study demonstrates that RV AGE causes a significant economic burden in China. Given the promising effectiveness and highly cost-effective, introduction of rotavirus vaccines in national immunization programs could substantially reduce the economic burden in China.
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Gastroenteritis , Infecciones por Rotavirus , Vacunas contra Rotavirus , Humanos , Lactante , Análisis Costo-Beneficio , Pueblos del Este de Asia , Gastroenteritis/epidemiología , Gastroenteritis/prevención & control , Gastroenteritis/virología , Vacunación Masiva , Estudios Prospectivos , Rotavirus , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/prevención & control , PreescolarRESUMEN
BACKGROUND: Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. METHODS: We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. RESULTS: During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. CONCLUSION: The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.
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Infecciones por Caliciviridae , Norovirus , Humanos , Lactante , Infecciones Asintomáticas/epidemiología , Infecciones por Caliciviridae/epidemiología , Estudios de Cohortes , Pueblos del Este de Asia , Heces , Genotipo , Epidemiología Molecular , Norovirus/genética , FilogeniaRESUMEN
BACKGROUND: We evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine. METHODS: In this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9-45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies. RESULTS: A total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMTHPV 16 = 10816 [95 % CI: 7824-14953]), GMTHPV 18 = 3966 [95 % CI: 2693-5841]) and high dose group (GMT HPV 16 = 14482 [95 % CI: 10848-19333], GMT HPV 18 = 3428 [95 % CI: 2533-4639]). CONCLUSION: The pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9-45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Vacunas de Partículas Similares a Virus , Femenino , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , China , Método Doble Ciego , Pueblos del Este de Asia , Virus del Papiloma Humano , Inmunogenicidad Vacunal , Papillomaviridae , Infecciones por Papillomavirus/prevención & control , Vacunas de Partículas Similares a Virus/efectos adversos , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana EdadRESUMEN
BACKGROUND: China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. METHODS: This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. RESULTS: There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test-positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. CONCLUSIONS: Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.
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Vacunas contra la COVID-19 , COVID-19 , Adulto , Humanos , Preescolar , COVID-19/prevención & control , Estudios Retrospectivos , China/epidemiología , Infecciones AsintomáticasRESUMEN
The effectiveness of the vero cell inactivated vaccine (CoronaVac®) against severe acute respiratory infection ( SARI) caused by SARS-CoV-2 in the real world was assessed. A matched test-negative case-control design was employed using the web-based national information system, as well as the hospitalization dataset in Sibu Hospital. Vaccine effectiveness was measured by conditional logistic regression with adjustment for gender, underlying comorbidity, smoking status, and education level. Between 15 March and 30 September 2021, 838 eligible SARI patients were identified from the hospitalization records. Vaccine effectiveness was 42.4% (95% confidence interval [CI]: -28.3 to 74.1) for partial vaccination (after receiving the first dose to 14 days after receiving the second dose), and 76.5% (95% CI: 45.6 to 89.8) for complete vaccination (at 15 days or more after receiving the second dose). This analysis indicated that two doses of CoronaVac® vaccine provided efficacious protection against SARI caused by SARS-CoV-2 in the short term. However, the duration of protection, and performance against new variants need to be studied continuously.
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COVID-19 , Neumonía , Vacunas , Chlorocebus aethiops , Animales , Humanos , Malasia/epidemiología , Células Vero , Estudios Retrospectivos , COVID-19/prevención & control , SARS-CoV-2RESUMEN
ObjectiveTwo COVID-19 outbreaks occurred in Henan province in early 2022-one was a Delta variant outbreak and the other was an Omicron variant outbreak. COVID-19 vaccines used at the time of the outbreak were inactivated, 91.8%; protein subunit, 7.5%; and adenovirus5-vectored, 0.7% vaccines. The outbreaks provided an opportunity to evaluate variant-specific breakthrough infection rates and relative protective effectiveness of homologous inactivated COVID-19 vaccine booster doses against symptomatic infection and pneumonia. DESIGN: Retrospective cohort study METHODS: We evaluated relative vaccine effectiveness (rVE) with a retrospective cohort study of close contacts of infected individuals using a time-dependent Cox regression model. Demographic and epidemiologic data were obtained from the local Centers for Disease Control and Prevention; clinical and laboratory data were obtained from COVID-19-designated hospitals. Vaccination histories were obtained from the national COVID-19 vaccination dataset. All data were linked by national identification number. RESULTS: Among 784 SARS-CoV-2 infections, 379 (48.3%) were caused by Delta and 405 (51.7%) were caused by Omicron, with breakthrough rates of 9.9% and 17.8%, respectively. Breakthrough rates among boosted individuals were 8.1% and 4.9%. Compared with subjects who received primary vaccination series ≥180 days before infection, Cox regression modelling showed that homologous inactivated booster vaccination was statistically significantly associated with protection from symptomatic infection caused by Omicron (rVE 59%; 95% CI 13% to 80%) and pneumonia caused by Delta (rVE 62%; 95% CI 34% to 77%) and Omicron (rVE 87%; 95% CI 3% to 98%). CONCLUSIONS: COVID-19 vaccination in China provided good protection against symptomatic COVID-19 and COVID-19 pneumonia caused by Delta and Omicron variants. Protection declined 6 months after primary series vaccination but was restored by homologous inactivated booster doses given 6 months after the primary series.
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COVID-19 , Estados Unidos , Humanos , Vacunas de Productos Inactivados , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios Retrospectivos , Eficacia de las Vacunas , SARS-CoV-2RESUMEN
Using a three-prefecture, two-variant COVID-19 outbreak in Henan province in January 2022, we evaluated the associations of primary and booster immunization with China-produced COVID-19 vaccines and COVID-19 pneumonia and SARS-CoV-2 viral load among persons infected by Delta or Omicron variant. We obtained demographic, clinical, vaccination, and multiple Ct values of infections ≥3 years of age. Vaccination status was either primary series ≥180 days prior to infection; primary series <180 days prior to infection, or booster dose recipient. We used logistic regression to determine odds ratios (OR) of Delta and Omicron COVID-19 pneumonia by vaccination status. We analysed minimum Ct values by vaccination status, age, and variant. Of 826 eligible cases, 405 were Delta and 421 were Omicron cases; 48.9% of Delta and 19.0% of Omicron cases had COVID-19 pneumonia. Compared with full primary vaccination ≥180 days before infection, the aOR of pneumonia was 0.48 among those completing primary vaccination <180 days and 0.18 among booster recipients among these Delta infections. Among Omicron infections, the corresponding aOR was 0.34 among those completing primary vaccination <180 days. There were too few (ten) Omicron cases among booster dose recipients to calculate a reliable OR. There were no differences in minimum Ct values by vaccination status among the 356 Delta cases or 70 Omicron cases. COVID-19 pneumonia was less common among Omicron cases than Delta cases. Full primary vaccination reduced pneumonia effectively for 6 months; boosting six months after primary vaccination resulted in further reduction. We recommend accelerating the pace of booster dose administration.
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COVID-19 , Neumonía , COVID-19/prevención & control , Vacunas contra la COVID-19 , China/epidemiología , Humanos , Inmunización Secundaria/métodos , SARS-CoV-2 , Carga ViralRESUMEN
BACKGROUND: The G8 rotavirus genotype has been detected frequently in children in many countries and even became the predominant strain in sub-Saharan African countries, while there are currently no reports from China. In this study we described the genetic characteristics and evolutionary relationship between rotavirus strains from Guangzhou in China and the epidemic rotavirus strains derived from GenBank, 2020-2021. METHODS: Virus isolation and subsequent next-generation sequencing were performed for confirmed G8P[8] specimens. The genetic characteristics and evolutionary relationship were analyzed in comparison with epidemic rotavirus sequences obtained from GenBank. RESULTS: The two Guangzhou G8 strains were DS-1-like with the closest genetic distance to strains circulating in Southeast Asia. The VP7 genes of the two strains were derived from a human, not an animal G8 rotavirus. Large genetic distances in several genes suggested that the Guangzhou strains may not have been transmitted directly from Southeast Asian countries, but have emerged following reassortment events. CONCLUSIONS: We report the whole genome sequence information of G8P[8] rotaviruses recently detected in China; their clinical and epidemiological significance remains to be explored further.
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Infecciones por Rotavirus , Rotavirus , Animales , Genoma Viral , Genotipo , Filogenia , Rotavirus/genética , Infecciones por Rotavirus/epidemiologíaRESUMEN
Waning of neutralizing titres along with decline of protection efficacy after the second dose of COVID-19 vaccines was observed, including China-made inactivated vaccines. Efficacy of a heterologous boosting using one dose of a recombinant SARS-CoV-2 fusion protein vaccine (V-01) in inactivated vaccine-primed population was studied, aimed to restore the immunity. A randomized, double-blind and placebo-controlled phase III trial was conducted in healthy people aged 18 years or older in Pakistan and Malaysia. Each eligible participant received one dose of the V-01 vaccine developed by Livzon Mabpharm Inc. or placebo within the 3-6 months after the two-dose primary regimen, and was monitored for safety and efficacy. The primary endpoint was protection against confirmed symptomatic SARS-CoV-2 infection. A total of 10,218 participants were randomly assigned to receive a vaccine or placebo. Virus-neutralizing antibodies were assessed in 419 participants. A dramatic increase (11.3-fold; 128.3-1452.8) of neutralizing titres was measured in the V-01 group at 14 days after the booster. Over two months of surveillance, vaccine efficacy was 47.8% (95%CI: 22.6-64.7) according to the intention-to-treat principle. The most common adverse events were transient, mild-to-moderate pain at the injection site, fever, headache, and fatigue. Serious adverse events occurred almost equally in V-01 (0.12%) and placebo (0.16%) groups. The heterologous boosting with the V-01 vaccine was safe and efficacious, which could elicit robust humoral immunity under the epidemic of the Omicron variant.Trial registration: ClinicalTrials.gov identifier: NCT05096832.
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Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Humanos , Inmunogenicidad Vacunal , Interferones , Proteínas Recombinantes de Fusión/genética , Vacunas de Productos InactivadosRESUMEN
Noroviruses (NoVs), a group of single-stranded RNA viruses causing epidemic acute gastroenteritis in humans, are highly diverse, consisting of multiple genogroups with >30 genotypes. Their continual evolutions make NoV vaccine design and development difficult. Here, we report a study of NoV sequences obtained from a population-based diarrhea surveillance in Zhengding County of Hebei Province spanning from 2001 to 2019 and those available in the GenBank database from 1966 to 2019. NoV genotypes and/or variants that may evade immunity were screened and identified based on primary and conformational structures for vaccine design. We selected 366, 301, 139, 74 and 495 complete VP1-coding nucleotide sequences representing the predominant genotypes of GII.4, GII.2, GII.3, GII.6 and GII.17, respectively. A total of 16 distinct GII.4 variants were identified, showing a typical linear evolutionary pattern of variant replacement, while only 1-4 variants of the other genotypes were found to co-circulate over the 40-50-year period without typical variant replacement. The vaccine strain GII.4c is close to variant Sydney_2012 (0.053) in their primary structure, but they are distinct at epitopes A and E in conformations. Our data suggested GII.4 variant Sydney_2012, GII.2 variant A, a GII.3 strain, GII.6 variants B and C and GII.17 variant D are primary candidate strains for NoV vaccine development.
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BACKGROUND: Diarrhea remains the leading cause of childhood illness in China. Better understanding of burden and etiology of diarrheal diseases is important for development of effective prevention measures. METHODS: Population-based diarrhea surveillance was conducted in Sanjiang (southern China) year-round and Zhengding (northern China) in autumn/winter. Stool specimens were collected from children < 5 years of age experiencing diarrhea. The TaqMan Array Card (TAC), based on multiplex real-time PCR, was applied to detect multiple enteric microbial agents simultaneously. Results using these methods were compared to those derived from conventional PCR assays. RESULTS: During the study period, 6,380 children in Zhengding and 3,581 children in Sanjiang < 5 years of age participated. Three hundred and forty (31.2%) and 279 (22.9%) diarrhea episodes were identified as moderate-to-severe in the two counties, with incidence of 60.4 and 88.3 cases per 1,000 child-years in Zhengding and Sanjiang, respectively. The five most frequently detected bacterial and viral agents in Sanjiang were adenovirus, enterovirus, enteroaggregative Escherichia coli (EAEC), rotavirus, and sapovirus all the year round, while the most common viral agents in Zhengding were rotavirus, followed by astrovirus and adenovirus during the cool season. Compared to conventional PCR assay, the average incremental detection via the TAC method was twofold. CONCLUSION: Our study demonstrated high diversity and prevalence of multiple major bacterial and viral agents, including rotavirus and calicivirus, among children in China. Further studies are needed to define the public health significance of neglected but frequently detected pathogens such as EAEC, enterotoxigenic E. coli, Campylobacter, adenovirus, and enterovirus.
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Rotaviruses (RVs) are the leading cause of acute gastroenteritis in children, while histo-blood group antigens (HBGAs) are believed to be host attachment and susceptibility factors of RVs. A large case-control study nested in a population-based diarrhea surveillance targeting children <5 y of age was performed in rural Hebei province, north China. Saliva and serum samples were collected from all participants to determine HBGA phenotyping, FUT2 mutations, and RV IgG antibody titers. A logistic model was employed to assess the association between host HBGA secretor status and risk of RV infection. Among 235 RV cases and 680 non-diarrhea controls studied, 82.4% of participants were IgG positive by an average age of 77 months. Out of the 235 RV cases, 216 (91.9%) were secretors, whereas the secretor rate was 76.3% in the non-diarrhea controls, resulted in an adjusted OR of 3.0 (95%CI: 1.9-4.7, P < .0001) between the two groups. Our population-based case-control study indicated a strong association between host HBGA secretor status and risk of RV infection in Chinese children. The high prevalence of Lewis-positive secretor status strongly suggests that Chinese children may be genetically susceptible to current co-circulating RV strains, and thus, a universal childhood immunization program against RV disease should be successful in China.
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Infecciones por Rotavirus , Rotavirus , Estudios de Casos y Controles , Niño , China , Predisposición Genética a la Enfermedad , Genotipo , HumanosRESUMEN
BACKGROUND: To build the triple-negative breast cancer (TNBC) radiation resistance model in vitro and vivo, and screen the molecular markers that related to radiation resistance. METHODS: We used X-ray to irradiate MDA-MB-231 cells repeatedly to build radioresistant cell (231-RR), then select one gemcitabine-resistance of MDA-MB-231 cell (231-GEM). We screen differentially expressed genes of these cell lines. Then, we would select 2 genes of them associated with DNA damage repair or cell cycle, and build RNAi lentivirus vector to knock down related gene. We also used X-rays repeatedly exposure TNBC tumor xenograft to build tumor with radioresistance properties, and then verify previously screening differentially expressed genes using IHC. Finally, we used The Cancer Genome Atlas (TCGA) database to validate the relationships between radioresistance related genes and the prognosis of breast cancer. RESULTS: We got 161 up-regulated genes and 156 down-regulated genes from three cell lines. Cellular results show the 231-cell with knock-down CDKN1A or SOD2 gene, its radiation sensitivity was significantly enhanced. We successfully got the TNBC xenograft tumor with radioresistance properties. Immunohistochemical results show that the radioresistance of tumor tissue with higher p21 (CDKN1A encoding protein) and SOD2 expression (P<0.01). The prognosis of patients with low SOD2 expression is better than that of high expression, but have no statistical significance (P=0.119); patients with low CDKN1A expression is significantly better than high expression (P=0.000). Multivariate cox analysis manifest that CDKN1A gene expression level is an independent prognostic factor in breast cancer patient (P=0.008). CONCLUSIONS: Construction of radiation resistance cell and xenograft tumor with radio-resistant properties model for radiation biology research is feasible. High SOD2 and CDKN1A is associated with the poor prognosis in breast cancer patients. These two genes could be used as a predicted makers of breast cancer radiation sensitivity.
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BACKGROUND: Despite the considerable disease burden caused by the disease, rotavirus vaccine has not been introduced into routine national immunization schedule, and norovirus vaccines are being developed without a comprehensive understanding of gastroenteritis epidemiology. To bridge this knowledge gap, we investigated the disease burden of viral gastroenteritis in rural China. METHODS: Between October 2011 and December 2013, population-based surveillance was conducted in Zhengding and Sanjiang counties in China. Stool samples were collected from children <5 years of age with diarrhea. All specimens were tested for rotaviruses, noroviruses, sapoviruses, enteric adenoviruses, and astroviruses. RESULTS: The most common pathogen causing diarrhea was rotavirus (54.7 vs 45.6 cases/1,000 children/year in Zhengding and Sanjiang, respectively), followed by norovirus (28.4 vs 19.3 cases/1,000 children/year in Zhengding and Sanjiang, respectively). The highest incidence of these viruses was observed in children 6-18 months of age. Among the 5 viral pathogens, rotaviruses caused the most severe illness, followed by noroviruses. CONCLUSION: Rotavirus and norovirus are the 2 most important viral pathogens causing childhood diarrhea in both northern and southern China; they should be the major targets for viral gastroenteritis prevention strategies among children in China.
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Gastroenteritis/virología , Virosis/virología , Virus/aislamiento & purificación , Preescolar , China/epidemiología , Diarrea/epidemiología , Diarrea/virología , Heces/virología , Femenino , Gastroenteritis/epidemiología , Humanos , Incidencia , Lactante , Masculino , Vigilancia de la Población , Población Rural/estadística & datos numéricos , Virosis/epidemiología , Virus/clasificación , Virus/genéticaRESUMEN
Regulatory T cells (Tregs) play a crucial role in the control of the initiation and progression of type 1 diabetes (T1D). Various immunological interventions including those to ex vivo expansion Tregs transfer, in vivo induction of peripherally derived Treg (pTreg) have been considered as promising approaches for T1D therapy. In this study, we developed a novel tolerogenic vaccine using four autoantigenic peptides of islet-derived with cyclosporine A (CsA) as the pTreg inducer, designated as GAD-IN+CsA. This vaccine immunized into prediabetic NOD mice subcutaneously could induce IL-10 and TGF-ß expressing pTregs and lead to suppressing autoreactive T cells responses, resulting in the prevention of T1D in these animals. Furthermore, we demonstrated that CsA with autoantigenic peptides modulates dendritic cells (DCs) to become immature IL-10hiCD40lo DCs. Such modulated DCs could foster naïve CD4+CD25- T cell into Tregs when presenting antigen peptides in vitro. This novel approach offers an alternative strategy to induce pTregs to treat T1D.
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Diabetes Mellitus Tipo 1 , Vacunas , Animales , Ciclosporina , Células Dendríticas , Diabetes Mellitus Tipo 1/prevención & control , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Linfocitos T ReguladoresRESUMEN
The composition of glycan in immunoglobulin G (IgG) has shown to affect various diseases and can be regulated by drugs and preventive vaccination. A hepatitis B surface antigen (HBsAg)-hepatitis B immunoglobulin (HBIG) immune complex (YIC) therapeutic vaccine for chronic hepatitis B (CHB) patients has undergone clinical trials. To explore for markers of CHB, which could be associated with responsiveness to YIC therapeutic vaccine, serum IgG glycosylation in CHB patients was analyzed.Kinetic changes of serum galactosylated IgG in 53 hepatitis Be antigen (HBeAg)-positive CHB patients treated with YIC were monitored by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis. Whole blood cytokines were assayed by cytokine binding assay kits. All samples were back assayed before treatment, during therapy and follow-up for 6 months from a previous completed clinical trial.During YIC treatment, 26 patients with lower IgG galactosylation level at baseline [galactosylation level (Gal-ratio)â=â-0.29, 0.18 (mean, SD)] showed sustained increase of serum galactosylated IgG, and responded to YIC treatment by HBeAg seroconversion. While those who did not respond to YIC treatment [Gal-ratioâ=â-0.40, 0.15 (mean, SD)] failed to show similar changes. Furthermore, this kinetic increase of galactosylated IgG correlated with marked up-regulated IL-2 level, confirming that effective cellular immune responses have participated in responsiveness.For HBeAg-positive CHB patients lower serum IgG galactosylation level may serve as an indicator for selecting a suitable subpopulation of candidates for YIC therapeutic vaccination.
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Vacunas contra Hepatitis B/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/terapia , Inmunoglobulina G/sangre , Adulto , Biomarcadores/sangre , Método Doble Ciego , Femenino , Estudios de Seguimiento , Galactosa/metabolismo , Hepatitis B Crónica/sangre , Humanos , Interleucina-2/sangre , Masculino , Seroconversión , Resultado del Tratamiento , VacunaciónRESUMEN
In recent years, therapeutic monoclonal antibodies have made impressive progress, providing great benefit by successfully treating malignant and chronic inflammatory diseases. Monoclonal antibodies with broadly neutralizing effects against specific antigens, or that target specific immune regulators, manifest therapeutic effects via their Fab fragment specificities. Subsequently therapeutic efficacy is mediated mostly by interactions of the Fc fragments of the antibodies with their receptors (FcR) displayed on cells of the immune system. These interactions can trigger a series of immunoregulatory responses, involving both innate and adaptive immune systems and including cross-presentation of antigens, activation of CD8 + T cells and CD4 + T cells, phagocytosis, complement-mediated antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). The nature of the triggered effector functions of the antibodies is markedly affected by the glycosylation patterns of the Fc fragments. These can cause differences in the conformation of the heavy chains of antibodies, with resultant changes in antibody binding affinity and activation of the complement system. Studies of the Fc glycosylation profiles together with the associated Fc effector functions and FcR/CR interactions promoted interest and progress in engineering therapeutic antibodies. Furthermore, because antigen-antibody immune complexes (ICs) have shown similar actions, in addition to certain novel immunoregulatory mechanisms that also reshape immune responses, the properties of ICs are being explored in new approaches for prevention and therapy of diseases. In this review, both basic studies and experimental/clinical applications of ICs leading to the development of preventive and therapeutic vaccines are presented.