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1.
《Vaccine》2018,36(42):6325-6333
BackgroundOver the last decades, pertussis showed periodic increases in its incidence among adults, despite being a vaccine-preventable disease.MethodsThis phase III, multicenter, extension study (NCT00489970) was conducted in adults from the United States, followed at Year (Y) 5 and Y9 post-vaccination with a dose of reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine containing either 3 (Tdap-B group) or 5 pertussis components (Tdap-A group). Willing participants in Tdap groups and newly-recruited participants (Control group) received one Tdap-B dose at Y9. Antibody persistence (at Y5 and Y9) and safety of Tdap-B at Y9 were assessed. Non-inferiority of immune response elicited by 2 Tdap doses was evaluated at Y9: (i) versus one Tdap-B dose for diphtheria and tetanus in terms of seroprotection rates; (ii) for all antigens in terms of booster response rates (Tdap-B and Tdap-A groups versus Control group); and (iii) for pertussis antigens in terms of geometric mean concentrations (GMCs) versus a 3-dose series of a combined diphtheria-tetanus-acellular pertussis vaccine (DTPa) administered during infancy.Results1257 participants were enrolled at Y5 and 809 participants were vaccinated at Y9. Seroprotection rates in both Tdap groups were ≥98.4% and ≥98.0% (Y5) and ≥98.3% and ≥98.1% (Y9) for diphtheria and tetanus, respectively. For pertussis antigens, antibody concentrations above assay cut-offs were observed for ≥76.6% (Y5) and ≥84.9% (Y9) of participants in Tdap groups. At Y9, one month post-Tdap vaccination, comparable seroprotection/seropositivity rates and antibody GMCs were observed among groups. Non-inferiority of immune responses in both Tdap groups was demonstrated when compared to the Control group for diphtheria and tetanus and to a 3-dose DTPa series for pertussis antigens. Non-inferiority criteria in terms of booster response were not met for all antigens. No safety concerns were raised.ConclusionA second dose of Tdap-B administered in adults, 9 years after initial Tdap vaccination, is immunogenic and well-tolerated.  相似文献   

2.
《Vaccine》2020,38(36):5842-5850
IntroductionAcute norovirus gastroenteritis causes significant morbidity and in uncommon cases fatality in older adults. We investigated the safety and immunogenicity of bivalent virus-like particle (VLP) vaccine candidate formulations with and without monophosphoryl lipid A (adjuvant MPL) in this population.MethodsIn this phase II, double-blind, controlled trial 294 healthy adults, ≥ 60 years of age, were randomized (1:1:1:1) to four groups to receive one or two intramuscular immunizations 28 days apart, with 26 18–49 year-old controls who received one MPL-free dose. One-dose groups received placebo on Day 1. Vaccine formulations contained 15 μg GI.1 and 50 μg GII.4c VLP antigens and 500 μg Al(OH)3, with or without 15 μg MPL. We measured histo-blood group antigen blocking (HBGA) antibodies and ELISA Ig at Days 1, 8, 29, 57, 211 and 393, and avidity indices and cell-mediated immunity (CMI). Solicited local and systemic adverse events (AE) were assessed for 7 days and unsolicited AEs for 28 days after each injection.ResultsAfter one dose HBGA antibodies to both VLP antigens increased with similar kinetics and magnitude in all groups; geometric mean titres (GMTs) persisted above baseline through Day 393. GMTs were similar across age strata (18–49, 60–74, 75–84 and ≥ 85 years of age) and unaffected by a second vaccination or MPL. Total Ig showed similar responses. No clinically relevant differences or changes in avidity or CMI were observed between formulations. Both formulations were well tolerated with no vaccine-related SAEs, the most frequent AEs being mild injection site pain and fatigue.ConclusionsAdults over 60 years of age displayed no safety concerns and had similar immune responses to the norovirus VLP vaccine candidate as younger adults, unaffected by increasing age, a second dose or inclusion of MPL. This data supports the further development of the MPL-free vaccine candidate for older adults.  相似文献   

3.
The safety and reactogenicity of a booster dose of GSK Biologicals' hexavalent DTPa-HBV-IPV/Hib vaccine (N=4725) was compared with the separate administration of GSK Biologicals' DTPa-IPV/Hib and HBV vaccines (N=4474) in two open, randomized multicenter studies (A and B). Solicited symptoms occurring within 4 days of vaccination were recorded on diary cards and serious adverse events (SAEs) were collected throughout the study period. In Study A (N=1149), incidences of solicited symptoms were similar in both groups; there were no SAEs either reported within 4 days of vaccination or considered to be causally related to vaccination. In study B (N=8050), where fever was the only solicited symptom, rectal temperature > or =39.5 degrees C was observed in 2.5% and 2.8% of the subjects, respectively. Fever > or =40.0 degrees C was rare (0.6%), and only two cases of febrile convulsions were recorded during the 4 days following vaccination both in the control group. Large swelling reactions (defined as local injection site swelling with diameter >50 mm, noticeable diffuse injection site swelling or noticeable increased circumference of the injected limb) were reported following 2.3% of the booster vaccine doses, regardless of the vaccine used. Extensive swelling reactions involving an adjacent joint were reported in 0.1% of the subjects. Two SAEs, both reported after booster doses of DTPa-IPV/Hib and HBV vaccines administered separately, were considered by the investigators to be related to vaccination. Both resolved completely without sequelae. The hexavalent DTPa-HBV-IPV/Hib vaccine and the DTPa-IPV/Hib and HBV vaccines administered separately have similar good reactogenicity and safety profiles when given as booster doses in the second year of life.  相似文献   

4.
Meningococcal disease incidence is highest in young children, yet a tetravalent conjugate vaccine is currently not available for this age group. This study evaluated a single dose of four different ACWY-TT conjugate vaccine formulations in 240 toddlers (12–14 months) and 268 children (3–5 years) compared to licensed age-appropriate control vaccines. In toddlers, rSBA-MenC GMTs for the selected formulation were statistically higher than after monovalent-MenC-conjugate vaccine. In children, rSBA-GMTs against each serogroup were statistically higher than after tetravalent polysaccharide vaccine. The safety profile was comparable to licensed controls. The new ACWY-TT conjugate vaccine promises high seroprotection levels against meningococcal disease from 1 year of age.  相似文献   

5.
Three hundred and nineteen adolescents aged 10-12 years who had been previously vaccinated with five doses of acellular pertussis-containing vaccines received single doses of Tdap (reduced-antigen-content tetanus, diphtheria, acellular pertussis) and hepatitis A vaccines in a double-blind crossover trial. Long-term antibody persistence following vaccination with Tdap at pre-school age was similar to that following vaccination with DTaP (diphtheria-tetanus-acellular pertussis). After the sixth dose booster, Tdap induced a vigorous immune response, consistent with protection against diphtheria, tetanus and pertussis diseases.  相似文献   

6.
《Vaccine》2016,34(15):1832-1838
IntroductionThe United States experienced a substantial increase in reported pertussis cases over the last decade. Since 2005, persons 11 years and older have been routinely recommended to receive a single dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine. The objective of this analysis was to evaluate the potential impact and cost-effectiveness of recommending a second dose of Tdap.MethodsA static cohort model was used to calculate the epidemiologic and economic impact of adding a second dose of Tdap at age 16 or 21 years. Projected costs and outcomes were examined from a societal perspective over a 20-year period. Quality-adjusted Life Years (QALY) saved were calculated.ResultsUsing baseline pertussis incidence from the National Notifiable Diseases Surveillance System, Tdap revaccination at either age 16 or 21 years would reduce outpatient visits by 433 (5%) and 285 (4%), and hospitalization cases by 7 (7%) and 5 (5%), respectively. The costs per QALY saved with a second dose of Tdap were approximately US $19.7 million (16 years) and $26.2 million (21 years). In sensitivity analyses, incidence most influenced the model; as incidence increased, the costs per QALY decreased. To a lesser degree, initial vaccine effectiveness and waning of effectiveness also affected cost outcomes. Multivariate sensitivity analyses showed that under a set of optimistic assumptions, the cost per QALY saved would be approximately $163,361 (16 years) and $204,556 (21 years).ConclusionA second dose of Tdap resulted in a slight decrease in the number of cases and other outcomes, and that trend is more apparent when revaccinating at age 16 years than at age 21 years. Both revaccination strategies had high dollar per QALY saved even under optimistic assumptions in a multivariate sensitivity analysis.  相似文献   

7.
The Plasmodium falciparum AMA-1(III) and MSP1-19 proteins have been expressed as a chimera (PfCP-2.9), adjuvanted with Montanide ISA720 and developed as a vaccine candidate tested in human. The PfCP-2.9 protein contains 18 cysteine residues that form nine intramolecular disulfide bonds. The protective immune responses induced by the chimeric protein were dependent on its disulfide bond-based conformation. In this study, we developed a sandwich ELISA to assess the nature of the protein in the emulsion over time (6, 12 and 18 months). Our results showed that the OD450 values corresponding to vaccine storages were within the 95% confidence interval, indicating that the conformation of the protein in the emulsion stored for up to 18 months at 4 °C was unchanged. Furthermore, no protein degradation was detected by Coomassie blue, silver staining, and Western blot analysis for samples stored at 4 °C for up to 2 years. Although some protein aggregation was observed in the emulsion preparations, these aggregates were only a small percentage of the total protein in the sample (7.6%). Moreover, the protein multimers maintained their conformational epitope. The potency assay of the formulation showed no significant differences in ED50 values (50% effective dose for achieving seroconversion) between fresh vaccine formulations (ED50 = 0.057 ± 0.024 μg) and formulations stored for up to 6 (ED50 = 0.046 μg) or 12 months (ED50 = 0.040 μg). Importantly, the immune sera of rabbits immunized with formulations stored for 0, 3, 6, 9 and 12 months effectively inhibited parasite growth in vitro at similar levels. These data indicated that the vaccine emulsion was stable over long periods of storage and maintained both its physical and biological properties.  相似文献   

8.
Zheng Q  Fan D  Gao N  Chen H  Wang J  Ming Y  Li J  An J 《Vaccine》2011,29(4):763-771
Dengue is one of the most important mosquito-borne viral diseases. In past years, although considerable effort has been put into the development of a vaccine, there is currently no licensed dengue vaccine. In this study, we constructed DNA vaccines that carried the prM-E-NS1 genes of dengue virus serotype 1 (DV1) with or without the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene, an attractive DNA vaccine adjuvant. Immunization with the plasmid pCAG-DV1/E/NS1, which expresses viral prM-E-NS1, or the bicistronic plasmid pCAG-DV1-GM, which co-expresses viral prM-E-NS1 and GM-CSF, resulted in long-term IgG response, high levels of splenocyte-secreted interferon-γ and interleukin-2, strong cytotoxic T lymphocyte activity and sufficient protection in the DV1-challenged mice. This suggested that both humoral and cellular immune responses were induced by the immunizations and that they played important roles in protection against the DV1 challenge. Interestingly, the magnitude, quality and protective capacity of the immune responses induced by immunization with pCAG-DV1/E/NS1 or pCAG-DV1-GM seemed stronger than those induced by pCAG-DV1/E (expressing viral prM-E alone). Taken together, we demonstrated that prM/E plus NS1 would be a suitable solution for the development of a DNA vaccine against DV.  相似文献   

9.
10.
Reduced-antigen-content diphtheria-tetanus-acellular-pertussis (dTpa) vaccines are predominantly recommended for once-in-a-lifetime use. A second dTpa (Boostrix™, GlaxoSmithKline Biologicals) administration in 164 adults previously vaccinated with dTpa 10 years previously was evaluated. Before the decennial booster, 89.4% and 94.8% subjects were seroprotected (antibodies ≥0.1 IU/mL) for diphtheria and tetanus, respectively. One-month post-booster, all subjects were seroprotected/seropositive against all vaccine antigens. Robust GMC increases indicated a booster response similar to the first booster. The decennial booster was well tolerated without serious adverse events, consistent with product experience. This study supports replacing traditional Td boosters with dTpa, and use of Boostrix™ as a decennial booster.This study is registered at www.clinicaltrials.comNCT00548171.  相似文献   

11.
The present study aimed to identify and measure the relationship between malnutrition and psychosocial care in the second year of life. A case-control study compared 101 malnourished 12-23-month-old children (weight-for-age < 5th percentile, WHO/NCHS) to 200 well-nourished children (weight-for-age > 25th percentile) for exposure to various maternal behaviors related to psychosocial care. A psychosocial care score was constructed, based on the number of desirable maternal behaviors that were absent (the higher the score, the worse the quality of childcare). The association was modified by per capita family income. After adjusting for possible confounders, children from higher-income households showed no association between psychosocial care and malnutrition. For children from lower-income households, worse psychosocial care doubled the risk of malnutrition (OR = 7.26; 95%CI: 2.42-21.82) compared to low income alone (OR = 3.08; 95%CI: 1.28-7.42).  相似文献   

12.
《Vaccine》2022,40(10):1472-1482
BackgroundIncreased influenza vaccine efficacy is needed in the elderly at high-risk for morbidity and mortality due to influenza infection. Adjuvants may allow hemagglutinin (HA) dose-sparing with enhanced immunogenicity. MAS-1 is an investigational water-in-oil emulsion-based adjuvant/delivery system comprised of stable nanoglobular aqueous droplets.MethodsA phase 1, randomized, double-blind, safety and immunogenicity, adjuvant dose escalation trial was conducted in persons aged 65 years and older. MAS-1 adjuvant dose volumes at 0.3 mL or 0.5 mL containing 9 µg per HA derived from licensed seasonal trivalent influenza vaccine (IIV, Fluzone HD 60 µg per HA, Sanofi Pasteur) were compared to high dose (HD) IIV (Fluzone HD). Safety was measured by reactogenicity, adverse events, and safety laboratory measures. Immunogenicity was assessed by serum hemagglutination inhibition (HAI) antibody titers.ResultsForty-five subjects, aged 65–83 years, were randomly assigned to receive 9 µg per HA in 0.3 mL MAS-1 (15 subjects) or HD IIV (15 subjects) followed by groups randomly assigned to receive 9 µg per HA in 0.5 mL MAS-1 (10 subjects) or HD IIV (5 subjects). Injection site tenderness, induration, and pain, and headache, myalgia, malaise and fatigue were common, resolving before day 14 post-vaccination. Clinically significant late-onset injection site reactions occurred in four of ten subjects at the 0.5 mL adjuvant dose. Safety laboratory measures were within acceptable limits. MAS-1-adjuvanted IIV enhanced mean antibody titers, mean-fold increases in antibody titer, and seroconversion rates against vaccine strains for at least 168 days post-vaccination and enhanced cross-reactive antibodies against some non-study vaccine influenza viruses.ConclusionMAS-1 adjuvant provided HA dose-sparing without safety concerns at the 0.3 mL dose, but the 0.5 mL dose caused late injection site reactions. MAS-1-adjuvanted IIV induced higher HAI antibody responses with prolonged durability including against historical strains, thereby providing greater potential vaccine efficacy in the elderly throughout an influenza season.Clinical Trial Registry: ClinicalTrials.gov # NCT02500680.  相似文献   

13.
Photobacterium damselae subsp. piscicida (PDP) is the causative agent of fish pasteurellosis, a bacterial disease causing important losses in marine aquaculture. Vaccines against the pathogen can be a way to control the infection and avoid antibiotic treatments. However, a satisfactory protective vaccine against fish pasteurellosis is not commercially available. In this study, a biotechnogical approach based on reverse vaccinology has been used to identify potential vaccine candidates for the development of a recombinant subunit vaccine. Genome sequencing of clones from a genomic cosmid library of PDP and in silico selection of the surface exposed proteins were the initial steps in vaccine candidate identification. From 370 open reading frames (ORF) eight potential antigens were selected, expressed as recombinant proteins and purified. These vaccine candidates were used to generate specific polyclonal antibodies in mice. Each antibody was then screened in vitro by inhibition adherence assay of live PDP on chinook salmon embryo cells (CHSE-214). A lipoprotein, found to be involved in the adherence of the bacterium to epithelial cells and annotated as PDP_0080, was then selected. The recombinant protein was further investigated in fish vaccination and challenge experiments to assess its ability to protect sea bass, Dicentrarchus labrax, against PDP infection. Immunisation with PDP_0080 recombinant protein elicited high specific antibody titres. Furthermore, the survival rate of fish immunized with the 25 μg dose of protein was significantly higher compared to the control group. The results of the study suggest that the PDP_0080 protein could be a promising candidate for the design of a recombinant vaccine against pasteurellosis.  相似文献   

14.
OBJECTIVE: To assess the influence of feeding practices on the prevalence of anemia among breast-fed children, based on the nutritional profile of children receiving care at an outpatient pediatric clinic in the city of Rio de Janeiro, Brazil. METHODS: This was a cross-sectional study with 288 children between 12 and 18 months of age who were seen at the outpatient clinic between January and June 1993. The children were assessed in terms of the presence of iron-deficiency anemia. In addition, two questionnaires were done with the child's mother or the other person who had brought the child to the clinic: a 24-hour dietary recall and a record of the frequency of the consumption of iron-rich foods. RESULTS: Of the 288 children, 144 of them had signs of anemia (hemoglobin < 11 g/dL); of these 144, 38 of them had severe anemia (hemoglobin < 9.5 g/dL). We found low levels of bioavailable iron in the foods consumed, limited consumption of meat, and vitamin C consumption separate from meals. We found a significant association between the prevalence of severe anemia and inadequate iron intake (relative risk = 2.28; 95% confidence interval = 1.12 to 4.66; P = 0.02). The intake of bioavailable iron was higher in the group without anemia (P = 0.04). CONCLUSIONS: Individuals caring for breast-fed children should be educated concerning the nutritional contents of complementary foods so as to increase the bioavailability of iron in the children's diets. One way to achieve this objective might be through "Integrated Management of Childhood Illnesses," a strategy endorsed by a number of international organizations as a way to reduce child mortality and morbidity in developing countries.  相似文献   

15.
There is still no consensus on the question whether it is necessary to use prophylactic antibiotic therapy and on the febrile states in infectious diseases. The present study aims at solving these problems. Between 1996 and 1997, 128 children under one year of age with upper respiratory tract infections (URTI) were hospitalized in the department and examined using clinical, laboratory and instrumental methods. We found no significant difference in the percentage of complications in the children treated with or without antibiotics. We conclude that prophylactic antibiotic therapy is not justified for the predominating viral etiology of URTI in children less than one year old. URTIs can be managed without antipyretics, which entails no risk for the patients.  相似文献   

16.
This study describes the identification of the Plasmodium vivax rhoptry antigen Pv34 whose sequence was obtained based on homology comparison with the Plasmodium falciparum Pf34. The pv34 gene product was characterized by molecular biology and immunological techniques. Additionally, association of Pv34 to detergent-resistant microdomains (DRMs), expression in late blood-stage parasites and recognition of recombinant Pv34 (rPv34) by sera from P. vivax-infected Aotus monkeys and patients was assessed. Lymphoproliferation and cytokine secretion was also evaluated in individuals living in malaria endemic areas. Altogether, the data support carrying out further studies to assess the immunogenicity and protection-inducing ability of rPv34 as component of a multi-antigenic, multi-stage vaccine against vivax malaria.  相似文献   

17.
Objectives: This study aimed to assess the validity of COOP charts in a general population sample, to examine whether illustrations contribute to instrument validity, and to establish general population norms. Methods: A general population mail survey was conducted among 20–79 years old residents of the Swiss canton of Vaud. Participants were invited to complete COOP charts, the SF-36 Health Survey; they also provided data on health service use in the previous month. Two thirds of the respondents received standard COOP charts, the rest received charts without illustrations. Results: Overall 1250 persons responded (54%). The presence of illustrations did not affect score distributions, except that the illustrated physical fitness chart drew greater non-response (10 vs. 3%, p < 0.001). Validity tests were similar for illustrated and picture-less charts. Factor analysis yielded two principal components, corresponding to physical and mental health. Six COOP charts showed strong and nearly linear relationships with corresponding SF36 scores (all p < 0.001), demonstrating concurrent validity. Similarly, most COOP charts were associated with the use of medical services in the past month. Only the chart on social support partly deviated from construct validity hypotheses. Population norms revealed a generally lower health status in women and an age-related decline in physical health. Conclusions: COOP charts can be used to assess the health status of a general population. Their validity is good, with the possible exception of the social support chart. The illustrations do not affect the properties of this instrument.  相似文献   

18.
The optimal amount of vegetable consumption required to reduce chronic disease risk is widely debated. Intervention trials evaluating biological activity of vegetables at various doses are limited. We conducted a 3-dose, crossover feeding trial to test the hypothesis that vegetable intake is associated in a dose-dependent manner with increased plasma carotenoids and subsequently reduced oxidative stress and inflammation in 49 overweight, postmenopausal women. Participants were assigned in random order to 2 (130 g), 5 (287 g), and 10 (614 g) daily servings of fresh, greenhouse-grown vegetables for 3-wk intervals with a 4-wk washout period between treatments. Plasma total carotenoids significantly increased from 1.63 to 2.07 μmol/L with a dose of 2 vegetable servings, from 1.49 to 2.84 μmol/L with a dose of 5 vegetable servings, and from 1.40 to 4.42 μmol/L with a dose of 10 vegetable servings (pre-post paired ttests, all P < 0.001). The change during each feeding period increased with each dose level (P < 0.001). Urine concentrations of 8-isoprostane F2α, hexanoyl lysine, and serum high sensitivity C-reactive protein were not affected by any administered vegetable dose. In this variable-dose vegetable study, a dose-response for plasma carotenoids was demonstrated without significant change in oxidative stress and inflammation in overweight, postmenopausal women.  相似文献   

19.
After priming with two intramuscular doses of MF59®-adjuvanted (Sub/MF59) or split influenza vaccines during the 2006/07 season, 89 healthy children received a third booster dose of the respective vaccine (2007/08 Northern Hemisphere formulation) approximately 1 year later, and were followed up for 6 months post-third injection. Immunogenicity was evaluated on 81 of them by a hemagglutination inhibition (HI) assay before and 3 weeks after vaccination.  相似文献   

20.
Our study investigated health service use for people in the last year of life, comparing those who died with and without Alzheimer's disease (AD) documented on the death certificate. Using a population-based retrospective cohort design, and utilizing the Western Australian Data Linkage System for the period 2000–2002 (2.5 years), the study found that 992 people died of either AD alone or AD with at least one other condition recorded on the death certificate. Of those with documented AD, 90.4% were aged 75 or more years, two-thirds were female (68.8%), more than one-half were widowed (59.3%) and the majority lived in a major city (77.0%). Most deceased people had comorbidities recorded on death certificates (90.0%); the majority having either two (34.5%) or three (28.8%) comorbid conditions. Over two-thirds of people aged over 75 years with AD died in a residential aged care facility (RACF, 67.4%), while the greatest proportion of people without AD died in hospital (52.9%). When a comparison was made in the use of hospital and community-based services for decedents aged over 75 years with and without AD, dissimilarities were evident. Less than one-half of people with documented AD received hospital care in the last year of life (46.3%) compared to over 80% of people without AD (80.5%). Likewise, fewer people in the Alzheimer's group received community care when compared to those without documented AD (10.8% vs. 28.5%). Despite a small group of people with AD (5.4%) who were transferred to an RACF shortly before dying, most people in this group lived and died in an RACF and had their care provided in this setting. Adequate nursing, medical and allied health services, and the provision of appropriate social support, including the use of advance care directives in RACFs, are essential for equitable provision of care to people with AD.  相似文献   

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