64 research outputs found

    Randomized, Controlled Trial of the Long Term Safety, Immunogenicity and Efficacy of RTS,S/AS02(D) Malaria Vaccine in Infants Living in a Malaria-Endemic Region.

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    The RTS,S/AS malaria candidate vaccine is being developed with the intent to be delivered, if approved, through the Expanded Programme on Immunization (EPI) of the World Health Organization. Safety, immunogenicity and efficacy of the RTS,S/AS02(D) vaccine candidate when integrated into a standard EPI schedule for infants have been reported over a nine-month surveillance period. This paper describes results following 20 months of follow up. This Phase IIb, single-centre, randomized controlled trial enrolled 340 infants in Tanzania to receive three doses of RTS,S/AS02(D) or hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received DTPw/Hib (diphtheria and tetanus toxoids, whole-cell pertussis vaccine, conjugated Haemophilus influenzae type b vaccine) at the same timepoints. The study was double-blinded to month 9 and single-blinded from months 9 to 20. From month 0 to 20, at least one SAE was reported in 57/170 infants who received RTS,S/AS02(D) (33.5%; 95% confidence interval [CI]: 26.5, 41.2) and 62/170 infants who received hepatitis B vaccine (36.5%; 95% CI: 29.2, 44.2). The SAE profile was similar in both vaccine groups; none were considered to be related to vaccination. At month 20, 18 months after completion of vaccination, 71.8% of recipients of RTS,S/AS02(D) and 3.8% of recipients of hepatitis B vaccine had seropositive titres for anti-CS antibodies; seroprotective levels of anti-HBs antibodies remained in 100% of recipients of RTS,S/AS02(D) and 97.7% recipients of hepatitis B vaccine. Anti-HBs antibody GMTs were higher in the RTS,S/AS02(D) group at all post-vaccination time points compared to control. According to protocol population, vaccine efficacy against multiple episodes of malaria disease was 50.7% (95% CI: -6.5 to 77.1, p = 0.072) and 26.7% (95% CI: -33.1 to 59.6, p = 0.307) over 12 and 18 months post vaccination, respectively. In the Intention to Treat population, over the 20-month follow up, vaccine efficacy against multiple episodes of malaria disease was 14.4% (95% CI: -41.9 to 48.4, p = 0.545). The acceptable safety profile and good tolerability of RTS,S/AS02(D) in combination with EPI vaccines previously reported from month 0 to 9 was confirmed over a 20 month surveillance period in this infant population. Antibodies against both CS and HBsAg in the RTS,S/AS02(D) group remained significantly higher compared to control for the study duration. Over 18 months follow up, RTS,S/AS02(D) prevented approximately a quarter of malaria cases in the study population. CLINICAL TRIALS: Gov identifier: NCT00289185

    Development of standardized laboratory methods and quality processes for a phase III study of the RTS, S/AS01 candidate malaria vaccine

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    BACKGROUND\ud \ud A pivotal phase III study of the RTS,S/AS01 malaria candidate vaccine is ongoing in several research centres across Africa. The development and establishment of quality systems was a requirement for trial conduct to meet international regulatory standards, as well as providing an important capacity strengthening opportunity for study centres.\ud \ud METHODS\ud \ud Standardized laboratory methods and quality assurance processes were implemented at each of the study centres, facilitated by funding partners.\ud \ud RESULTS\ud \ud A robust protocol for determination of parasite density based on actual blood cell counts was set up in accordance with World Health Organization recommendations. Automated equipment including haematology and biochemistry analyzers were put in place with standard methods for bedside testing of glycaemia, base excess and lactacidaemia. Facilities for X-rays and basic microbiology testing were also provided or upgraded alongside health care infrastructure in some centres. External quality assurance assessment of all major laboratory methods was established and method qualification by each laboratory demonstrated. The resulting capacity strengthening has ensured laboratory evaluations are conducted locally to the high standards required in clinical trials.\ud \ud CONCLUSION\ud \ud Major efforts by study centres, together with support from collaborating parties, have allowed standardized methods and robust quality assurance processes to be put in place for the phase III evaluation of the RTS, S/AS01 malaria candidate vaccine. Extensive training programmes, coupled with continuous commitment from research centre staff, have been the key elements behind the successful implementation of quality processes. It is expected these activities will culminate in healthcare benefits for the subjects and communities participating in these trials.\ud \ud TRIAL REGISTRATION\ud \ud Clinicaltrials.gov NCT00866619

    Evaluation of the Safety and Immunogenicity of the RTS,S/AS01E Malaria Candidate Vaccine When Integrated in the Expanded Program of Immunization

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    Background. The RTS,S/AS01E malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI). Methods. This phase 2, randomized, open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01E when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01E at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and wholecell pertussis conjugate [DTPw]; hepatitis B [HepB]; Haemophilus influenzae type b [Hib]; and oral polio vaccine [OPV]), RTS,S/AS01E at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only. Results. The occurrences of serious adverse events were balanced across groups; none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01E coadministration groups. RTS,S/AS01E generated high anti-circumsporozoite protein and anti- hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01E at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups. Conclusion. RTS,S/AS01E integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007. GlaxoSmithKline study ID number: 106369 (Malaria-050

    Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection

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    The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF50) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines

    A Search for Technosignatures Around 31 Sun-like Stars with the Green Bank Telescope at 1.15-1.73 GHz

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    We conducted a search for technosignatures in April of 2018 and 2019 with the L-band receiver (1.15-1.73 GHz) of the 100 m diameter Green Bank Telescope. These observations focused on regions surrounding 31 Sun-like stars near the plane of the Galaxy. We present the results of our search for narrowband signals in this data set as well as improvements to our data processing pipeline. Specifically, we applied an improved candidate signal detection procedure that relies on the topographic prominence of the signal power, which nearly doubles the signal detection count of some previously analyzed data sets. We also improved the direction-of-origin filters that remove most radio frequency interference (RFI) to ensure that they uniquely link signals observed in separate scans. We performed a preliminary signal injection and recovery analysis to test the performance of our pipeline. We found that our pipeline recovers 93% of the injected signals over the usable frequency range of the receiver and 98% if we exclude regions with dense RFI. In this analysis, 99.73% of the recovered signals were correctly classified as technosignature candidates. Our improved data processing pipeline classified over 99.84% of the ~26 million signals detected in our data as RFI. Of the remaining candidates, 4539 were detected outside of known RFI frequency regions. The remaining candidates were visually inspected and verified to be of anthropogenic nature. Our search compares favorably to other recent searches in terms of end-to-end sensitivity, frequency drift rate coverage, and signal detection count per unit bandwidth per unit integration time.Comment: 20 pages, 8 figures, in press at the Astronomical Journal (submitted on Sept. 9, 2020; reviews received Nov. 6; re-submitted Nov. 6; accepted Nov. 17

    Possible quenching of static neutron pairing near the N=98 deformed shell gap: Rotational structures in Gd-160,Gd-161

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    A Gd160 beam was accelerated to an energy of 1000 MeV and, separately, bombarded thick targets of Sm154 and Dy164 in order to observe neutron-rich, rare-earth nuclei via deep-inelastic collision processes. Gammasphere was utilized to observe ?-ray emissions. Many new states and transitions were observed in Gd160 as a result of so-called unsafe Coulomb excitation. The ground-state band in Gd160 has been extended to Ip=20+ and a rotational band based on the Kp=4+ state, previously associated with a hexadecapole vibration, was observed up to 18+. The quasiparticle configuration of the Kp=4+ band has been determined, and its unusual alignment behavior may result from a possible quenching of static neutron pairing. In addition, the band based on the [523]5/2 quasineutron orbital in Gd161 was extended from 11/2- to 33/2- and also displays the same unusual alignment behavior

    Possible quenching of static neutron pairing near the N=98 deformed shell gap: Rotational structures in Gd 160,161

    Get PDF
    A Gd160 beam was accelerated to an energy of 1000 MeV and, separately, bombarded thick targets of Sm154 and Dy164 in order to observe neutron-rich, rare-earth nuclei via deep-inelastic collision processes. Gammasphere was utilized to observe ?-ray emissions. Many new states and transitions were observed in Gd160 as a result of so-called unsafe Coulomb excitation. The ground-state band in Gd160 has been extended to Ip=20+ and a rotational band based on the Kp=4+ state, previously associated with a hexadecapole vibration, was observed up to 18+. The quasiparticle configuration of the Kp=4+ band has been determined, and its unusual alignment behavior may result from a possible quenching of static neutron pairing. In addition, the band based on the [523]5/2 quasineutron orbital in Gd161 was extended from 11/2- to 33/2- and also displays the same unusual alignment behavior
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