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1.
Mohamed F. Jalloh Mohammad B. Jalloh Alison Albert Brent Wolff Amy Callis Aparna Ramakrishnan Emily Cramer Paul Sengeh Samuel Abu Pratt Lansana Conteh Rana Hajjeh Rebecca Bunnell John T. Redd Anna Mia Ekström Helena Nordenstedt 《Vaccine》2019,37(11):1495-1502
Introduction
Experimental Ebola vaccines were introduced during the 2014–2015 Ebola outbreak in West Africa. Planning for the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) was underway in late 2014. We examined hypothetical acceptability and perceptions of experimental Ebola vaccines among health care workers (HCWs), frontline workers, and the general public to guide ethical communication of risks and benefits of any experimental Ebola vaccine.Methods
Between December 2014 and January 2015, we conducted in-depth interviews with public health leaders (N?=?31), focus groups with HCWs and frontline workers (N?=?20), and focus groups with members of the general public (N?=?15) in Western Area Urban, Western Area Rural, Port Loko, Bombali, and Tonkolili districts. Themes were identified using qualitative content analysis.Results
Across all participant groups, not knowing the immediate and long-term effects of an experimental Ebola vaccine was the most serious concern. Some respondents feared that experimental vaccines may cause Ebola, lead to death, or result in other adverse events. Among HCWs, not knowing the level of protection provided by experimental Ebola vaccines was another concern. HCWs and frontline workers were motivated to help find a vaccine for Ebola to help end the outbreak. General public participants cited positive experiences with routine childhood immunization in Sierra Leone.Discussion
Our formative assessment prior to STRIVE’s implementation in Sierra Leone helped identify concerns, motivations, and information gaps among potential participants of an experimental Ebola vaccine trial, at the time when an unprecedented outbreak was occurring in the country. The findings from this assessment were incorporated early in the process to guide ethical communication of risks and benefits when discussing informed consent for possible participation in the vaccine trial that was launched later in 2015. 相似文献2.
Sung-Ching Pan Szu-Min Hsieh Chih-Feng Lin Yu-Shen Hsu Mingi Chang Shan-Chwen Chang 《Vaccine》2019,37(14):1994-2003
Background
A nasal influenza vaccine has been available only in a live attenuated form, which limits the range of recipients to immune-competent individuals. The present study evaluated a newly developed intranasal inactivated influenza vaccine with a novel adjuvant, heat-labile enterotoxin (LT) derived from E. coli (LTh(αK)).Methods
The study was a randomized, double-blind, controlled phase I trial to evaluate the safety and immunogenicity of an intranasal vaccine containing the trivalent influenza HA antigen (7.5?µg each of A/California/7/09 (H1N1)-like virus, A/Victoria/210/2009 (H3N2) virus, and B/Brisbane/60/2008-like virus) in combination with 4 different doses of adjuvant LTh(αK) (7.5, 15, 30 or 45?μg) and 22.5?μg of influenza HA antigen alone (control vaccine). The vaccine was intranasally administered on Days 0 and 7. A safety evaluation commenced for 180?days, and hemagglutination inhibition (HI) antibody titers and nasal HA-specific IgA titers on Day 0 and Day 28 were assessed to determine whether an immunogenic response was elicited.Results
From November 2012 to September 2013, a total of 36 subjects were enrolled. Twenty-four subjects received an adjuvanted vaccine, and 12 subjects received a control vaccine. The most common adverse event (AE) was mild nasal discomfort, and systemic AEs were mild fatigue and headache. Only two subjects discontinued the study because of an AE (one had grade 3 fever, and one had nodal arrhythmia). In the group with 45?μg of LTh(αK), the seroprotection rates were 100%, 100% and 80%, and the nasal IgA conversion factors were 7.90, 7.46 and 12.27 for the A/H3N2, A/H1N1 and split B strains, respectively. Adjuvant LTh(αK) vaccine showed a significant enhancement in mucosal immunity in split B -specific IgA.Conclusion
The intranasal inactivated influenza vaccine is generally safe, and the LTh(αK)-adjuvanted vaccine is more immunogenic than non-adjuvanted control vaccine.ClinicalTrials.gov Identifier: NCT03293732. 相似文献3.
Li-Min Huang Cheng-Hsun Chiu Nan-Chang Chiu Chien-Yu Lin Ming-Ta Li Tsun-Yung Kuo Yi-Jen Weng Erh-Fang Hsieh I-Chen Tai 《Vaccine》2019,37(13):1827-1835
Background
To fight against enterovirus A71 (EV-A71)-associated diseases, vaccine development was initiated in Taiwan focusing on two-month-old infants.Methods
We conducted a phase II, double-blind, randomised, placebo-controlled study on infants and children aged two months to 11?years. This study was conducted in 4 parts (2a, 2b, 2c, and 2d) with age de-escalation sequentially. Two doses were administered with a 28-day or 56-day interval. Participants aged two months to <two years received a booster dose at one year after the first dose. During the surveillance period, solicited adverse events (AEs) and unsolicited AEs were recorded for safety evaluation. Blood samples were collected for neutralising antibody assay at various times. Immune persistence and booster effects were also assessed.Results
A total of 363 children completed the study. Most AEs were mild and unrelated to treatment. No vaccine-related serious adverse events (SAEs) were reported. Geometric mean titres (GMTs) of serum neutralising antibody titres increased profoundly. Most participants in the vaccine groups achieved defined seroprotection (neutralization titre?≥?1:32) after the second vaccination and persisted for two years. Furthermore, the EV-A71 vaccine could provide a cross-reaction against other EV-A71 strain genotypes: B5, C4a, C4b, and C5.Conclusions
The mid dose of the EV-A71 vaccine elicited high immune response and were tolerable in participants aged between two months and 11?years in all dosing groups. 相似文献4.
Stephanie Pepin Martin Dupuy Charissa Fay Corazon Borja-Tabora May Montellano Lulu Bravo Jaime Santos Jo-Anne de Castro Doris Maribel Rivera-Medina Clare Cutland Miguel Ariza Javier Diez-Domingo Celia Diaz Gonzalez Federico Martinón-Torres Efimia Papadopoulou-Alataki Maria Theodoriadou Marie Pierre Kazek-Duret Sanjay Gurunathan Iris De Bruijn 《Vaccine》2019,37(13):1876-1884
Background
A quadrivalent split-virion inactivated influenza vaccine (VaxigripTetra?, Sanofi Pasteur; IIV4) containing two A strains (H1N1 and H3N2) and B strains from both lineages (Victoria and Yamagata) was approved in Europe in 2016 for individuals aged?≥?3?years. This study examined the efficacy and safety of IIV4 in children aged 6–35?months.Methods
This was a phase III randomised controlled trial conducted in Latin America, Asia, Africa, and Europe during the Northern Hemisphere 2014/2015 and 2015/2016 and Southern Hemisphere 2014 and 2015 influenza seasons. Healthy children aged 6–35?months not previously vaccinated against influenza were randomised to receive two full doses 28?days apart of IIV4, placebo, the licensed trivalent split-virion inactivated vaccine (IIV3), an investigational IIV3 containing a B strain from the alternate lineage. The primary objective was to demonstrate efficacy against influenza illness caused by any strain or vaccine-similar strains.Results
The study enrolled 5806 participants. Efficacy, assessed in 4980 participants completing the study according to protocol, was demonstrated for IIV4. Vaccine efficacy was 50.98% (97% CI, 37.36–61.86%) against influenza caused by any A or B type and 68.40% (97% CI, 47.07–81.92%) against influenza caused by vaccine-like strains. Safety profiles were similar for IIV4, placebo, and the IIV3s, although injection-site reactions were slightly more frequent for IIV4 than placebo.Conclusions
IIV4 was safe and effective for protecting children aged 6–35?months against influenza illness caused by vaccine-similar or any circulating strains.Clinical trial registration
EudraCT no. 2013-001231-51. 相似文献5.
Hiroshige Mikamo Yuka Yamagishi Shinya Murata Ruriko Yokokawa Shi Rong Han Akira Wakana Miyuki Sawata Yoshiyuki Tanaka 《Vaccine》2019,37(12):1651-1658
Background
The quadrivalent (q) human papillomavirus (HPV) vaccine protects against infection and disease related to HPV types 6, 11, 16, and 18. We report efficacy, immunogenicity, and safety of qHPV vaccine in a Phase 3 study in Japanese men.Methods
In this randomized, double-blind trial (NCT01862874), Japanese men (aged 16–26?years) were randomized in a 1:1 ratio to receive three doses of qHPV vaccine or placebo (Day 1, Month 2, Month 6). The primary efficacy endpoint was the combined incidence of HPV6/11/16/18-related persistent anogenital infection (detected at ≥2 consecutive visits ≥6?months apart), assessed in the per-protocol population of men who received all three vaccinations, and were seronegative at Day 1 and PCR negative from Day 1 to Month 7 to the relevant HPV type. Results are from the interim and final analyses.Results
In total, 1124 participants were randomized. The vaccine demonstrated 83.3% (95% confidence interval: 24.9, 98.2; p?=?0.007) and 85.9% (95% confidence interval: 52.7, 97.3; p?<?0.001) efficacy against HPV6/11/16/18-related persistent infection in the interim and final analyses, respectively. Two cases of HPV6/11/16/18-related external genital lesions (condyloma and PIN 1) were observed in the placebo group and none in the qHPV vaccine group at study end. At Month 7, >97% of participants who received qHPV vaccine seroconverted to each of the vaccine HPV types. Most participants remained seropositive at Month 36, although the seropositivity rate declined between Months 7 and 36. Vaccination-related adverse events were reported in 60.8% and 56.5% of participants in the qHPV vaccine and placebo groups, respectively; most commonly mild to moderate injection-site pain, erythema, and swelling. Injection-site pain and swelling were more common with qHPV vaccine than placebo (each p?<?0.05).Conclusions
Results suggest qHPV vaccine is efficacious against HPV6/11/16/18-related persistent infections, immunogenic, and well-tolerated in Japanese men.Clinical trial registration identifier: NCT01862874. 相似文献6.
Stephanie Pepin Sandrine I. Samson Fabian P. Alvarez Martin Dupuy Viviane Gresset-Bourgeois Iris De Bruijn 《Vaccine》2019,37(13):1885-1888
Background
A multi-season phase III trial conducted in the Northern and Southern Hemispheres demonstrated the efficacy of a quadrivalent split-virion inactivated influenza vaccine (IIV4) in children 6–35?months of age.Methods
Data collected during the phase III trial were analysed to examine the vaccine efficacy (VE) of IIV4 in preventing laboratory-confirmed influenza in age subgroups and to determine the relative risk for IIV4 vs. placebo for severe outcomes, healthcare use, and parental absenteeism from work associated with laboratory-confirmed influenza.Results
VE (95% confidence interval [CI]) to prevent laboratory-confirmed influenza due to any A or B strain was 54.76% (40.24–66.03%) for participants aged 6–23?months and 46.91% (23.57–63.53%) for participants aged 24–35?months. VE (95% CI) to prevent laboratory-confirmed influenza due to vaccine-similar strains was 74.51% (53.55–86.91%) for participants aged 6–23?months and 59.78% (19.11–81.25%) for participants aged 24–35?months. Compared to placebo, IIV4 reduced the risk (95% CI) by 31.28% (8.96–89.34%) for acute otitis media, 21.76% (6.46–58.51%) for acute lower respiratory infection, 40.80% (29.62–55.59%) for healthcare medical visits, 29.71% (11.66–67.23%) for parent absenteeism from work, and 39.20% (26.89–56.24%) for antibiotic use.Conclusion
In children aged 6–35?months, vaccination with IIV4 reduces severe outcomes of influenza as well as the associated burden for their parents and the healthcare system. In addition, vaccination with IIV4 is effective at preventing against influenza in children aged 6–23 and 24–35?months.Trial registration: EudraCT no. 2013-001231-51. 相似文献7.
Wen Chen Yun Zhao Xing Xie Jihong Liu Jingran Li Chao Zhao Shaoming Wang Xueyan Liao Qiong Shou Minghuan Zheng Alfred J Saah Lihui Wei Youlin Qiao 《Vaccine》2019,37(6):889-897
Background
A quadrivalent human papillomavirus (qHPV) vaccine (HPV6/11/16/18) has demonstrated efficacy and acceptable safety in international studies. However, these studies did not include participants from mainland China, which has a substantial burden of HPV-related disease. This is the first safety report with a follow-up period of up to 90?months from a randomized, double-blind, placebo-controlled trial of qHPV vaccine in Chinese women 20–45?years of age.Methods
Participants were randomized 1:1 to receive three doses of qHPV vaccine or placebo (Day 1, Month 2, and Month 6). Efficacy outcomes are reported elsewhere. Injection-site and systemic adverse events (AEs) were collected using vaccination report cards (VRCs) for 15?days following each vaccination. Serious AEs (SAEs), pregnancy outcomes, new medical conditions, and fetal/infant SAEs were collected during the entire study.Results
Of 3006 participants randomized, AEs were reported by 926 (61.8%) qHPV vaccine recipients and 856 (57.1%) placebo recipients over the entire study. Four participants (two in each group) discontinued the study vaccination due to AEs that were considered vaccination-related. Within 15?days following any vaccination, injection-site AEs prompted for on the VRC were more frequent among qHPV vaccine recipients (37.6% vs 27.8%), and systemic AEs prompted for on the VRC were similar in frequency between qHPV vaccine and placebo groups (46.8% vs 45.1%). Thirty-eight and 43 participants reported SAEs in qHPV vaccine and placebo groups, respectively. No SAE was considered qHPV vaccine-related. Pregnancy outcomes, fetal/infant SAEs, and new medical conditions were generally similar in frequency between the qHPV vaccine and placebo groups, and within normal ranges.Conclusion
The qHPV vaccine was well tolerated and demonstrated a favorable safety profile in Chinese women 20–45?years of age, consistent with findings from global trials and safety surveillance studies.Trial registration: clinicaltrials.gov; NCT00834106. 相似文献8.
David I. Bernstein Derek A. Pullum Rhonda D. Cardin Fernando J. Bravo David A. Dixon Konstantin G. Kousoulas 《Vaccine》2019,37(1):61-68
Background
Although development of an HSV vaccine is a priority there is currently no vaccine available. The recent failure of subunit vaccines suggest that presentation of more antigens via a live attenuated vaccine may be required for protection. We therefore evaluated VC2, a live attenuated HSV vaccine, engineered to be unable to enter into neuronal axons.Methods
VC2 pathogenesis was first evaluated in guinea pigs following intravaginal inoculation. VC2 was then evaluated as a prophylactic and therapeutic vaccine and compared protection to a gD2 vaccine adjuvanted with MPL/Alum in the guinea pig model of genital HSV-2. The guinea pig model allows evaluation of acute and recurrent disease, as well as vaginal shedding acutely and during episodes of recurrent activation.Results
VC2 was significantly attenuated in guinea pigs compared to the wild type strain, 17syn+. It replicated poorly at the inoculation site, did not produce any genital disease and rarely infected the neural tissue. After prophylactic vaccination, the VC2 vaccine decreased the clinical severity of acute and recurrent HSV-2 disease and shedding and decreased the quantity of virus in the DRGs. When compared to gD2+MPL/Alum, VC2 was somewhat more effective especially as it relates to neural tissue infection. VC2 was not effective as a therapeutic vaccine.Conclusion
The live attenuated prophylactic HSV vaccine, VC2, was effective in the guinea pig model of genital HSV-2. Its decreased ability to infect neural tissues provides advantages over other live attenuated vaccines. 相似文献9.
Christian Selinger Anna Bershteyn Dobromir T. Dimitrov Blythe J.S. Adamson Paul Revill Timothy B. Hallett Andrew N. Phillips Linda-Gail Bekker Helen Rees Glenda Gray 《Vaccine》2019,37(16):2258-2267
Background
RV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individual-based network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective.Methods
Consistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24?months after the first dose and include two-yearly boosters that maintain durable efficacy over 10?years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions.Results
Our analysis shows that this partially effective vaccine could prevent, at catch-up vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750).Conclusions
While a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability. 相似文献10.
Kriengkrai Prasert Jayanton Patumanond Prabda Praphasiri Supakit Siriluk Darunee Ditsungnoen Malinee Chittaganpich Fatimah S. Dawood Joshua A. Mott Kim A. Lindblade 《Vaccine》2019,37(6):783-791
Background
We conducted a two-year prospective cohort study to measure the effectiveness of trivalent inactivated influenza vaccine (IIV3) to prevent laboratory-confirmed influenza among community-dwelling Thai adults aged ≥65?years during 2015–16 and 2016–17 influenza seasons.Methods
In 2015, we enrolled a cohort of 3220 participants. Trained health volunteers collected baseline data and followed participants for two years with weekly surveillance for new or worsened cough with self-collection of nasal swabs. Vaccine effectiveness (VE) was estimated as 100%?×?(1- rate ratio of rRT-PCR -confirmed influenza) among vaccinated versus unvaccinated participants. Propensity score stratification was used to reduce differences between vaccinated and unvaccinated participants associated with access to and receipt of IIV3.Findings
During 2015–16 and 2016–17, 1666 (52%) and 1498 (48%) participants received IIV3, respectively. The overall incidence of influenza during the two seasons was 14.3/1000 person-years among vaccinated participants and 20.2/1000 person-years among unvaccinated participants. VE was ?4% (95% confidence interval [CI], ?83%–40%) during 2015–16 when there was poor antigenic match between the dominant circulating A/H3N2 viruses and the vaccine strain, and 50% (95% CI, 12–71%) during 2016–17 when circulating and vaccine strains were well-matched. Of all three influenza subtypes in both years, significant protection was observed only against Influenza A/H3N2 during 2016–17 (VE, 49%; 95% CI, 3–73%).Interpretation
During a season with well-matched circulating and vaccine strains, IIV3 was moderately effective against laboratory-confirmed influenza among older adults in Thailand. 相似文献11.
A.F. Dempsey J. Pyrzanowski E.J. Campagna S. Lockhart S.T. O&#x;Leary 《Vaccine》2019,37(10):1307-1312
Objective
To assess secondary, parent-reported outcomes from a randomized controlled trial (RCT) of a provider communication intervention aimed at improving adolescent HPV vaccination.Methods
A paper survey was provided to a random sample of 777 parents of adolescents from 8 control and 8 intervention clinics participating in the larger trial. Chi-square or Fisher’s exact tests assessed associations between study arm and providers’ HPV vaccine communication strategies, parents’ vaccination attitudes and parent’s HPV vaccine acceptance. Exploratory analyses assessed the association between receipt of ‘very strong’ or presumptive HPV vaccine recommendation (regardless of study arm) and parent’s perceptions about their providers’ vaccine communication, and parents’ attitudes and acceptance of the HPV vaccine.Results
The response rate was 47%. There were no differences between study arms in parents’ report of how their provider communicated about the HPV vaccine, parent vaccination attitudes, or uptake of the HPV vaccine. Receipt of a ‘very strong’ recommendation was associated with greater perceived urgency for getting vaccinated, greater trust in the information received from the provider, decreased vaccine hesitancy, and increased vaccine receipt. Receipt of a presumptive recommendation was associated with a lower likelihood of having concerns about the vaccine’s safety, lower vaccine hesitancy, and an increased likelihood of vaccination. Neither recommendation strategy appeared to negatively impact parents’ visit experience or trust in the information being provided. Similar results were found in sub-analyses of vaccine hesitant parents.Conclusions
Providing very strong, presumptive HPV vaccine recommendations is associated with improved parent vaccination attitudes and acceptance, and does not seem to have significant negative impacts, even among parents who are vaccine hesitant. Response bias in our sample could explain why there were no reported differences between study arms in parents’ reports of how their adolescent’s providers communicated about the HPV vaccine. 相似文献12.
Penina Haber Pedro L. Moro Carmen Ng Graça M. Dores Paige Lewis Maria Cano 《Vaccine》2019,37(11):1516-1520
Background
Trivalent adjuvanted influenza vaccine (aIIV3; Fluad®) was approved in the United States (U.S.) in 2015 for adults aged ≥65?years and has been in use since the 2016–17 influenza season.Methods
We analyzed U.S. reports for aIIV3 submitted from July 1, 2016 through June 30, 2018 to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. Medical records were reviewed for serious reports. Among individuals ≥65?years of age, the relative frequency of the most commonly reported adverse events (AEs) after aIIV3 were compared with non-adjuvanted inactivated influenza vaccines given to adults aged ≥65?years, high-dose trivalent influenza vaccine (IIV3-HD) and trivalent or quadrivalent vaccines (IIV3/IIV4). Data mining analyses were undertaken to identify whether AEs for aIIV3 occurred disproportionately more than expected compared to all influenza vaccines.Results
VAERS received 630 reports after aIIV3, of which 521 (83%) were in adults aged ≥65?years; 79 (13%) in persons <65?years and in 30 (5%) reports age was missing; 19 (3%) reports were serious, including two deaths (0.4%) related to myocardial infarction and Sjogren’s syndrome. The most common AEs reported in adults aged ≥65?years were injection site pain (21%) and erythema (18%), with similar proportions reported for IIV3-HD (17% and 19%, respectively) and for IIV3/IIV4 (15%, each). Except for reports related to vaccination of inappropriate age (n?=?79) and syringe malfunction (n?=?6), data mining did not identify other disproportionately reported AEs.Conclusions
Although our review of aIIV3 in VAERS did not identify any unexpected health conditions of concern, we observed more than twice the expected number of reports with administration of the vaccine to persons outside of the age range for which the vaccine is approved in the U.S. Health care providers should be educated on the age groups for whom aIIV3 is recommended. 相似文献13.
Wivine Burny Arnaud Marchant Caroline Hervé Andrea Callegaro Magalie Caubet Laurence Fissette Lien Gheyle Catherine Legrand Cheikh Ndour Fernanda Tavares Da Silva Robbert van der Most Fabienne Willems Arnaud M. Didierlaurent Juan Yarzabal 《Vaccine》2019,37(14):2004-2015
Background
Adjuvants like AS01B increase the immunogenicity of vaccines and generally cause increased transient reactogenicity compared with Alum. A phase II randomized trial was conducted to characterize the response to AS01B and Alum adjuvanted vaccines. A post-hoc analysis was performed to examine the associations between reactogenicity and innate immune parameters.Methods
The trial involved 60 hepatitis B-naïve adults aged 18–45?years randomized 1:1 to receive either two doses of HBsAg-AS01B on Day (D)0 and D30, or three doses of HBsAg-Alum on D0, D30, D180. Prior to vaccination, all subjects received placebo injection in order to differentiate the impact of injection process and the vaccination. Main outcomes included reactogenicity symptoms, vital signs, blood cytokines, biochemical and hematological parameters after vaccination. Associations were explored using linear regression.Findings
The vaccine with AS01B induced higher HBsAg-specific antibody levels than Alum. Local and systemic symptoms were more frequent in individuals who received HBsAg AS01B/Alum vaccine or placebo, but were mild and short-lived. Blood levels of C-reactive protein (CRP), bilirubin, leukocyte, monocyte and neutrophil counts increased rapidly and transiently after AS01B but not after Alum or placebo. Lymphocyte counts decreased in the AS01B group and lactate dehydrogenase levels decreased after Alum. Modelling revealed associations between systemic symptoms and increased levels of CRP and IL-6 after the first HBsAg-AS01B or HBsAg-Alum immunization. Following the second vaccine dose, CRP, IL-6, IP-10, IFN-γ, MIP-1β and MCP-2 were identified as key parameters associated with systemic symptoms. These observations were confirmed using an independent data set extracted from a previous study of the immune response to HBsAg-adjuvanted vaccines (NCT00805389).Conclusions
IL-6 and IFN-γ signals were associated with systemic reactogenicity following administration of AS01B-adjuvanted vaccine. These signals were similar to those previously associated with antibody and T-cell responses induced by HBsAg-adjuvanted vaccines, suggesting that similar innate immune signals may underlie adjuvant reactogenicity and immunogenicity.Trial registration: www.clinicaltrials.gov NCT01777295. 相似文献14.
Janna R. Shapiro Breanna Hodgins Hilary E. Hendin Aakash Patel Karim Menassa Celine Menassa Maurice Menassa Jennifer A. Pereira Brian J. Ward 《Vaccine》2019,37(10):1332-1339
Background
Needle-free vaccine delivery systems have many potential advantages including increased vaccine compliance and decreased risk of needlestick injuries and syringe reuse. The Med-Jet® H4 is a gas-powered, auto-disabling disposable syringe jet injector. The Med-Jet family of products are currently being used in dermatology, podiatry, pain management and veterinary practices. The objectives of this study were to assess patient attitudes, time-efficiency, safety and immunogenicity of the seasonal influenza vaccine delivered by Med-Jet compared to the traditional needle-and-syringe.Methods
A total of 80 patients were randomized 2:1:1 to receive a commercial trivalent vaccine by Med-Jet or needle injection from a single-dose or multi-dose vial. Patient attitudes were assessed pre-randomization and post-immunization. Safety data were collected for 21?days post-immunization. Efficiency of vaccine administration was measured through a time-and-motion study. Humoral and cellular responses were assessed on Days 0 and 21.Results
Overall, the participants readily accepted Med-Jet vaccination despite greater frequency of transient local reactions (eg: redness, swelling) immediately following immunization. Vaccine administration took slightly longer with the Med-Jet, but this difference decreased over time. Geometric mean hemagglutination inhibition titers, seroconversion and seroprotection rates in the Med-Jet and needle groups were equivalent for all influenza strains in the vaccine. Microneutralization responses were also essentially identical. There were no significant differences between the groups in the frequency of functional CD4?+?T cells, memory subset distribution or poly-functionality.Conclusions
These data suggest that the Med-Jet is an acceptable means of delivering seasonal influenza vaccine. The system was attractive to subjects, rapidly learned by skilled vaccine nurses and elicited both humoral and cellular responses that were indistinguishable from those elicited with needle injection. While other studies have assessed the humoral response to jet injection of influenza vaccine, to our knowledge, this study is the first to assess the cellular aspect of this response. (ClinTrials.gov-NCT03150537). 相似文献15.
Yinong Young-Xu Julia Thornton Snider Robertus van Aalst Salaheddin M. Mahmud Edward W. Thommes Jason K.H. Lee David P. Greenberg Ayman Chit 《Vaccine》2019,37(11):1484-1490
Background
Observational studies of the relative effectiveness of influenza vaccines are essential for public health decision making. Their estimates, however, are subject to bias due to unmeasured confounders. Instrumental variable (IV) methods can control for observed and unobserved confounders.Methods
We used linked electronic medical record databases in the Veterans Health Administration (VHA) as well as Medicare administrative files to examine the relative vaccine effectiveness (rVE) of high-dose influenza vaccine (HD) versus standard-dose influenza vaccines (SD) in preventing hospitalizations among VHA-enrolled Veterans ≥65?years of age during 5 influenza seasons (2010–2011 through 2014–2015). Using multivariable IV Poisson regression modeling to address unmeasured confounding and bias, we analyzed the data by each season and through longitudinal analysis of all five seasons.Findings
We included 3,638,924 person–influenza seasons of observation where 158,636 (4%) were among HD vaccine recipients and 3,480,288 (96%) were among SD vaccine recipients. Of the 1,728,562 Veterans, 1,702,824 (98.5%) were male and 1,299,412 (75%) were non-Hispanic white. Based on the longitudinal analysis of all five seasons, the IV-adjusted rVE estimate of HD vs. SD was 10% (95% CI, 8–12%) against all-cause hospitalization; 18% (95% CI, 15–21%) against cardiorespiratory-associated hospitalization; and 14% (95% CI, 6–22%) against influenza/pneumonia-associated hospitalization. The findings by season were similar.Interpretation
Our analysis of VHA clinical data collected from approximately 1.7 million Veterans 65?years and older during five seasons demonstrates that high-dose influenza vaccine is more effective than standard-dose influenza vaccines in preventing influenza- or pneumonia-associated hospitalizations, cardiorespiratory hospitalizations, and all-cause hospitalizations. 相似文献16.
Background
The current Ebola outbreak in Eastern Democratic Republic of the Congo (DRC) is the second largest in history and the first in which the recombinant Vesicular Stomatitis Virus – Zaire Ebolavirus (rVSV-ZEBOV) vaccine has been used at scale. We assessed side-effects, satisfaction, and attitudes toward the new vaccine.Methods
Cross-sectional survey questionnaire from a convenience sample of 90 vaccine recipients and 96 community controls in Eastern DRC.Results
Side-effects were reported in 75/90 (83%) vaccine recipients but only 5 (7%) and 4 (5%) reported arthralgia and rash, respectively. 76/90 (84%) vaccinees were classified as “promoters” (would recommend vaccine to others) and 6/90 (7%) as “detractors.” 69/96 (72%) of unvaccinated community controls would wish to be vaccinated if supply were available. 153/186 (82%) would accept vaccination for family members.Conclusions
The rVSV-ZEBOV vaccine was well tolerated, with high acceptability in the community during the current outbreak in the DRC. 相似文献17.
Camila H. Coelho Pedro Henrique Gazzinelli-Guimaraes Jennifer Howard Emma Barnafo Nada A.H. Alani Olga Muratova Ashley McCormack Emily Kelnhofer Joseph F. Urban David L. Narum Charles Anderson Jean Langhorne Thomas B. Nutman Patrick E. Duffy 《Vaccine》2019,37(8):1038-1045
Introduction
Malaria transmission blocking vaccines (TBV) are innovative approaches that aim to induce immunity in humans against Plasmodium during mosquito stage, neutralizing the capacity of the infected vectors to transmit malaria. Pfs230D1-EPA/Alhydrogel®, a promising protein-protein conjugate malaria TBV, is currently being tested in human clinical trials in areas where P. falciparum malaria is coendemic with helminth parasites. Helminths are complex metazoans that share the master capacity to downregulate the host immune response towards themselves and also to bystander antigens, including vaccines. However, it is not known whether the activity of a protein-based malaria TBV may be affected by a chronic helminth infection.Methods
Using an experimental murine model for a chronic helminth infection (Heligmosomoides polygyrus bakeri - Hpb), we evaluated whether prior infection alters the activity of Pfs230D1-EPA/Alhydrogel® TBV in mice.Results
After establishment of a chronic infection, characterized by a marked increase of parasite antigen-specific IgG1, IgA and IgE antibody responses, concomitant with an increase of systemic IL-10, IL-5 and IL-6 levels, the Hpb-infected mice were immunized with Pfs230D1-EPA/Alhydrogel® and the vaccine-specific immune response was compared with that in non-infected immunized mice. TBV immunizations induced an elevated vaccine specific-antibody response, however Pfs230D1 specific-IgG levels were similar between infected and uninfected mice at days 15, 25 and 35 post-vaccination. Absolute numbers of Pfs230D1-activated B cells generated in response to the vaccine were also similar among the vaccinated groups. Finally, vaccine activity assessed by reduction of oocyst number in P. falciparum infected mosquitoes was similar between Hpb-infected and immunized mice with non-infected immunized mice.Conclusion
Pfs230D1-EPA/Alhydrogel® efficacy is not impaired by a chronic helminth infection in mice. 相似文献18.
Marta López-Fauqued Laura Campora Frédérique Delannois Mohamed El Idrissi Lidia Oostvogels Ferdinandus J. De Looze Javier Diez-Domingo Thomas C. Heineman Himal Lal Janet E. McElhaney Shelly A. McNeil Wilfred Yeo Fernanda Tavares-Da-Silva 《Vaccine》2019,37(18):2482-2493
Background
The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.Methods
Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30?days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12?months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period.Results
Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race.Conclusions
No safety concerns arose, supporting the favorable benefit-risk profile of RZV. 相似文献19.
Megumi Inoue Takuma Yonemura Richard de Solom Masako Yamaji Masakazu Aizawa Charles Knirsch Michael W. Pride Kathrin U. Jansen William Gruber Chris Webber 《Vaccine》2019,37(19):2600-2607
Background
Clostridium difficile infection (CDI) is a major global cause of nosocomial and community-acquired infections. Despite potentially severe or fatal complications and frequent recurrence, no preventive vaccine is currently available. This randomized, observer-blinded, placebo-controlled phase 1 study in older Japanese adults evaluated safety and immunogenicity of an investigational C difficile vaccine containing a mixture of genetically detoxified and chemically inactivated toxoids, A and B.Methods
Healthy Japanese adults aged 65 to 85?years were randomized in a 3:3:2 ratio to receive 100 or 200?μg of C difficile vaccine or placebo, respectively, at 0, 1, and 6?months (month regimen) or 1, 8, and 30?days (day regimen). The primary objective was safety evaluation. Vaccine immunogenicity, the secondary objective, was determined by assessing toxin A– and toxin B–specific neutralizing antibody levels in human sera.Results
Local reactions were reported by up to 33.3% of subjects per dose in the month regimen; percentages were generally higher in the 200-μg group. Such reactions were all mild or moderate in severity and generally transient. No adverse events in the month regimen led to subject withdrawal, and no serious adverse events were considered vaccine related. Further enrollment and dosing in the day regimen were discontinued after 3 subjects in the 100-μg group reported severe redness after dose 2. In the month regimen study arm, immune responses as measured by toxin-neutralizing antibody geometric mean concentrations, geometric mean fold rises, and proportions of subjects achieving prespecified fold rises were generally higher in the 200-μg group, peaked at month 7, and remained elevated at month 12.Conclusions
The C difficile vaccine candidate was safe, well tolerated, and immunogenic when administered to healthy older Japanese adults at 0, 1, and 6?months. Results support continued development of the vaccine for the prevention of CDI.ClinicalTrials.gov identifier: NCT02725437. 相似文献20.
Sandra Crouse Quinn Amelia M. Jamison Ji An Gregory R. Hancock Vicki S. Freimuth 《Vaccine》2019,37(9):1168-1173
