129 research outputs found
Evaluation of a multiplexed immunoassay for assessing long-term humoral immunity Orthopoxviruses
No full textCRediT authorship contribution statement Bethany Hicks: Writing – review & editing, Writing – original draft, Methodology, Investigation, Formal analysis, Conceptualization. Scott Jones: Writing – review & editing, Supervision, Methodology, Investigation, Conceptualization. Helen Callaby: Writing – review & editing. Daniel Bailey: Writing – review & editing. Claire Gordon: Writing – review & editing. Tommy Rampling: Writing – review & editing. Catherine Houlihan: Writing – review & editing. Ezra Linley: Writing – review & editing. Simon Tonge: Writing – review & editing. Clarissa Oeser: Writing – review & editing. Rachael Jones: Writing – review & editing. Marcus Pond: Writing – review & editing. Ravi Mehta: Writing – review & editing. Deborah Wright: Writing – review & editing. Bassam Hallis: Writing – review & editing, Funding acquisition. Cathy Rowe: Writing – review & editing, Funding acquisition. Ashley Otter: Writing – review & editing, Supervision, Methodology, Funding acquisition, Conceptualization.Peer reviewe
Optimising the Timing of whooping cough Immunisation in MUMs (OpTIMUM): A randomised controlled trial investigating the timing of pertussis vaccination in pregnancy
No full textBackground: Pertussis is a highly infectious respiratory illness caused by the bacteria Bordetella pertussis. A resurgence of pertussis, even in countries with good vaccine coverage, has led to an increase in infant deaths. In response to this, many countries have introduced pertussis vaccination in pregnancy. This strategy is effective at preventing infant disease, but there remains uncertainty about what gestational timing is best to ensure maximal protection of the infant. These uncertainties are the rationale for this randomised controlled trial and a sub-study investigating pertussis-specific antibody in breastmilk. Protocol: We will recruit 354 pregnant women and will randomise them to receive their pertussis vaccination in one of three gestational age windows: ≤23+6, 24-27+6 and 28-31+6 weeks of gestation. Vaccination will be with Boostrix-IPV® and participants will be asked to complete a symptom diary for seven days following vaccination. Blood sampling will be performed prior to vaccination, two weeks following vaccination and at the time of delivery. A cord blood sample will be collected at delivery and a blood sample collected from the infant 4-10 weeks after completion of the primary immunisations. Individuals participating in the breastmilk sub-study will provide a sample of colostrum within 48 hours of delivery and samples of breastmilk at two weeks and around five-six months. Blood samples will be analysed using enzyme linked immunosorbent assay (ELISA) techniques for pertussis toxin, filamentous haemagglutinin and pertactin. A subset of serum samples will also be analysed using a functional assay. Colostrum and breastmilk samples will be analysed using functional assays.Discussion: Although pertussis vaccination has been shown to be safe and effective in pregnancy there remains debate about the optimal timing for the administration during pregnancy. This study will investigate antibody responses in serum and breastmilk when vaccination is performed in three different time periods.Clinicaltrials.gov registration: NCT03908164 (09/04/2019
A phase IV, multi-centre, randomized clinical trial comparing two pertussis-containing vaccines in pregnant women in England and vaccine responses in their infants
No full textBackground: Pertussis vaccines containing three or five pertussis antigens are recommended in pregnancy in many countries, but no studies have compared the effect on infants’ antigen-specific immunoglobulin G (IgG) concentrations. The aim of this study was to compare anti-pertussis IgG responses following primary immunization in infants of mothers vaccinated with TdaP
5-IPV (low dose diphtheria toxoid, tetanus toxoid, acellular pertussis [five antigens] and inactivated polio) or TdaP
3-IPV in pregnancy (three pertussis antigens). Methods: This multi-centre phase IV randomized clinical trial was conducted in a tertiary referral centre and primary care sites in England. Women were randomized to receive TdaP
5-IPV (n = 77) or TdaP
3-IPV (n = 77) at 28–32 gestational weeks. A non-randomized control group of 44 women who had not received a pertussis-containing vaccine in pregnancy and their 47 infants were enrolled post-partum. Results: Following infant primary immunization, there was no difference in the geometric mean concentrations (GMCs) of anti-pertussis toxin, filamentous haemagglutinin or pertactin IgG between infants born to women vaccinated with TdaP
5-IPV (n = 67) or TdaP
3-IPV (n = 63). However, the GMC of anti-pertussis toxin IgG was lower in infants born to TdaP
5-IPV- and TdaP
3-IPV-vaccinated mothers compared to infants born to unvaccinated mothers (n = 45) (geometric mean ratio 0.71 [0.56–0.90] and 0.78 [0.61–0.98], respectively); by 13 months of age, this difference was no longer observed. Conclusion: Blunting of anti-pertussis toxin IgG response following primary immunization occurs in infants born to women vaccinated with TdaP
5-IPV and TdaP
3-IPV, with no difference between maternal vaccines. The blunting effect had resolved by 13 months of age. These results may be helpful for countries considering which pertussis-containing vaccine to recommend for use in pregnancy. Trial registration: ClinicalTrials.gov, NCT02145624, registered 23 May 2014
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An observational, cohort, multi-centre, open label phase IV extension study comparing preschool DTAP-IPV booster vaccine responses in children whose mothers were randomised to one of two pertussis-containing vaccines or received no pertussis-containing vaccine in pregnancy in England.
No full textAn antenatal pertussis vaccination programme was introduced in 2012 in the UK in the context of a national outbreak of pertussis. It has been shown that a lower antibody response to primary immunisation can be seen for certain pertussis antigens in infants born to women who received pertussis-containing antenatal vaccines, a phenomenon known as blunting. The longer-term impact of this has not been documented previously, and accordingly was evaluated in this study. Children were predominantly recruited from a previous study in which their mothers had received acellular pertussis-containing antenatal vaccines (dTaP3-IPV [diphtheria toxoid, tetanus toxoid, three antigen acellular pertussis and inactivated polio] or dTaP5-IPV [diphtheria toxoid, tetanus toxoid, five antigen acellular pertussis and inactivated polio]), or no pertussis-containing vaccine. Blood samples were obtained prior to and one month after the acellular pertussis-containing preschool booster (dTaP5-IPV) was given at around age 3 years 4 months. Pre- and post-booster immunoglobulin G (IgG) geometric mean concentrations (GMCs) against pertussis toxin, filamentous haemagglutinin, fimbriae 2 & 3, and pertactin, were compared. Prior to the receipt of the preschool booster, there was no difference in the IgG GMCs against pertussis-specific antigens between children born to women vaccinated with dTaP3-IPV and dTaP5-IPV; however, IgG GMCs against pertussis toxin were significantly lower in children born to women vaccinated with dTaP3-IPV compared with children born to unvaccinated women (geometric mean ratio 0.42 [95 % CI 0.22-0.78], p = 0.03). One month after the receipt of the preschool booster there was no differences between the groups. The blunting effect of antenatal pertussis vaccine on pertussis responses in children can persist until preschool age, although it is overcome by the administration of a booster dose. ClinicalTrials.gov registration number: NCT03578120
Antibody responses after primary immunization in infants born to women receiving a pertussis-containing vaccine during pregnancy: single arm observational study with a historical comparator.
No full textINTRODUCTION: In England, antenatal pertussis immunization using a tetanus/low-dose diphtheria/5-component acellular-pertussis/inactivated-polio (TdaP5/IPV) vaccine was introduced in October 2012. We assessed infant responses to antigens in the maternal vaccine and to those conjugated to tetanus (TT) or the diphtheria toxin variant, CRM. METHODS: Infants of 141 TdaP5/IPV-vaccinated mothers in Southern England immunized with DTaP5/IPV/Haemophilus influenzae b (Hib-TT) vaccine at 2-3-4 months, 13-valent pneumococcal vaccine (PCV13, CRM-conjugated) at 2-4 months and 1 or 2 meningococcal C vaccine (MCC-CRM- or MCC-TT) doses at 3-4 months had blood samples taken at 2 and/or 5 months of age. RESULTS: Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae 2 + 3 (FIMs), diphtheria, tetanus, Hib, MCC and PCV13 serotypes were compared to responses in a historical cohort of 246 infants born to mothers not vaccinated in pregnancy. Infants had high pertussis antibody concentrations pre-immunization but only PT antibodies increased post-immunization (fold-change, 2.64; 95% confidence interval [CI], 2.12-3.30; P < .001), whereas FHA antibodies fell (fold-change, 0.56; 95% CI, .48-.65; P < .001). Compared with infants of unvaccinated mothers, PT, FHA, and FIMs antibodies were lower post-vaccination, with fold-differences of 0.67 (0.58-0.77; P < .001), 0.62 (0.54-0.71; P < .001) and 0.51 (0.42-0.62; P < .001), respectively. Antibodies to diphtheria and some CRM-conjugated antigens were also lower, although most infants achieved protective thresholds; antibodies to tetanus and Hib were higher. CONCLUSIONS: Antenatal pertussis immunization results in high infant pre-immunization antibody concentrations, but blunts subsequent responses to pertussis vaccine and some CRM-conjugated antigens. In countries with no pertussis booster until school age, continued monitoring of protection against pertussis is essential
Internet outfitters: librarians in the twenty-first century
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Purpose
In the future, librarians need to prepare users to navigate a profoundly different informational landscape. Addressing issues of information overload and informed selection of both search tools and results, the purpose of this paper is to cast the collaborative relationship between librarian and student in the mode of an outfitter: a guide preparing a client for a journey. Within this context, the authors emerging role involves guiding students through the task at hand using critical thinking skills to access a wider range of publications to meet a broader range of needs.
Design/methodology/approach
Metaphors created by Raymond and Friedman reflect the current state of information, the relationship users have with these sources, and the role librarians play in a disintermediated environment. In The Cathedral and the Bazaar, Raymond portrays a decentralized environment as a bazaar. In The World is Flat 3.0, Friedman describes how technology flattens organizations through empowering end users. The informational landscape in the twenty-first century is decentralized, and more powerful search tools provide unparalleled access to these sources. Users, however, continue to experience problems finding their information. A librarian/outfitter can prepare users to effectively track information in the new environment.
Findings
In the twenty-first century, a broader range of sources are available, and search engines are turning to dashboards to prioritize the growing list of results. Users need to adapt to the new environment through viewing the search as an activity rather than a destination. Librarians can help this process through sharing their expertise in uncovering likely places relevant information may be found, in evaluating sources, and locating information in a larger context. Through developing the meta-skill of information management, librarians guide users through the process of finding information for personal, professional, and academic needs.
Practical implications
The author’s goal is what it has always been: empowering end users to successfully access needed information in a disintermediated environment. Today librarians need to emphasize a fundamentally different set of skills in the interactions they have with students and faculty. People can use dashboards and satisficing to find sources they need, but librarian/outfitters can introduce a broader range of sources and tools suitable for completing specific tasks. This paper illustrates the different skills needed to effectively find information for personal, professional, and academic tasks.
Originality/value
This paper provides a new context for the process used for locating and validating information in an increasingly broad and diffuse informational landscape. Librarians become advisors in navigating a more complex informational landscape that is used to meet a broader range of informational needs. While focusing on navigating the broader range of resources through decoding dashboards and satisficing techniques, the author can assist users in overcoming information overload and advocate a broader sense of satisficing through using more sophisticated critical thinking skills.
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Influenza A virus challenge models in cynomolgus macaques using the authentic inhaled aerosol and intra-nasal routes of infection
No full textNon-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis) are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units). This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation) and low to moderate doses (103 to 106 plaque forming units) of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units) did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common) influenza infections
Bacillus anthracis: Balancing innocent research with dual-use potential
No full textAnthrax Euronet, a Coordination Action of the EU 6th Framework Programme, was designed to strengthen networking activities between anthrax research groups in Europe and to harmonise protocols for testing anthrax vaccines and therapeutics. Inevitably, the project also addressed aspects of the current political issues of biosecurity and dual-use research, i.e. research into agents of important diseases of man, livestock or agriculture that could be used as agents of bioterrorism. This review provides a comprehensive overview of the biology of Bacillus anthracis, of the pathogenesis, epidemiology and diagnosis of anthrax, as well as vaccine and therapeutic intervention strategies. The proposed requirement for a code of conduct for working with dual-use agents such as the anthrax bacillus is also discussed
Optimising the timing of whooping cough immunisation in mums (OpTIMUM) through investigating pertussis vaccination in pregnancy: an open-label, equivalence, randomised controlled trial.
No full textBACKGROUND: Pertussis vaccination in pregnancy is recommended in many countries to provide protection to young infants. The best timing for this vaccination is uncertain. In the UK, vaccination is recommended between 16 weeks and 32 weeks of gestation. In this trial we aimed to investigate the equivalence of three time periods for pertussis vaccination in pregnancy. METHODS: In this open-label, equivalence, randomised controlled trial to investigate equivalence of different time windows for pertussis vaccination in pregnancy, participants were randomly assigned (1:1:1 ratio) to receive a pertussis-containing vaccine (Boostrix-inactivated poliovirus vaccine) in one of three gestational age groups, comprising group 1 (≤23 weeks + 6 days), group 2 (24-27 weeks + 6 days), and group 3 (28-31 weeks + 6 days) using a computer-generated randomisation list. The primary outcome was concentration of pertussis-specific antibodies in the infant born at term at birth. Maternal blood sampling was done before and 2 weeks after vaccination and at delivery, together with a cord sample, and an infant sample was collected at least 4 weeks after primary vaccination. Reactogenicity was assessed for 7 days after vaccination. This trial was registered with ClinicalTrials.gov (NCT03908164). FINDINGS: Between May 7, 2019, and Feb 13, 2020, of 1010 women assessed for eligibility, 364 women were recruited and 351 received the intervention (120 in group 1, 119 in group 2, and 112 in group 3). Equivalence of time periods was demonstrated for anti-pertussis toxin and anti-pertactin IgG concentrations. The cord blood geometric mean concentrations of anti-filamentous haemagglutinin IgG were higher with increasing gestational age at vaccination, such that for infants in group 1 (≤23 weeks + 6 days), equivalence to group 3 (28-31 weeks + 6 days) was not shown. Reported rates of fever were similar between study groups. INTERPRETATION: Pertussis vaccination at three different time intervals in pregnancy resulted in equivalent concentrations of IgG antibodies in infants against two of the three pertussis antigens assessed. Overall, these findings support recommendations to vaccinate any time between 16 weeks and 32 weeks of gestation. FUNDING: The Thrasher Research Fund and the National Immunisation Schedule Evaluation Consortium through the National Institute for Health and Care Research policy research programme
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