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In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design. In this work, Otter et al. compared the humoral immune responses induced by MPXV infection and Smallpox vaccination. Although comparable responses were observed, infection- or vaccination specific serological markers were identified enabling discrimination between vaccinated and infected individuals.

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

[...]in 2022 a global outbreak of Clade IIb mpox occurred spreading primarily within gay, bisexual, and other men-who-have-sex-with-men with more than 98 000 cases and 183 deaths across 118 countries.2 Clade I mpox remains isolated to endemic countries, such as the Democratic Republic of the Congo, but still causes considerable outbreaks.3 The Bavarian Nordic IMVANEX (ie, Jynneos) smallpox vaccine has been recommended by public health authorities worldwide because of its cross-protection against mpox disease. [...]while there is ongoing spread of mpox, there is a requirement for rapid diagnosis of cases (IgM detection) to confirm antibody status and inform on patient vaccination recommendations in at-risk individuals (eg, booster recommendations), or to conduct serosurveillance studies to establish the true spread of disease in a population. Serious considerations and validation should be made regarding the reliability and accuracy of such LFDs before they are recommended for widespread use in public health initiatives or population-level surveillance studies. 100 (2·50–100) 95·24 (74·37–99·28) Negative predictive value (%; 95% CI) 23·81 (23·81–23·81) 23·94 (22·85–25·08) 20·45 (19·57–21·37) 21·62 (21·62–21·62) 27·59 (24·60–30·79) 23·81 (23·81–23·81) 23·61 (22·73–24·52) 20·00 (20·00–20·00) 21·92 (21·34–22·51) 28·85 (24·38–33·76) Table Characteristics and performance of mpox lateral flow devices

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic in 2020. Testing is crucial for mitigating public health and economic effects. Serology is considered key to population-level surveillance and potentially individual-level risk assessment. However, immunoassay performance has not been compared on large, identical sample sets. We aimed to investigate the performance of four high-throughput commercial SARS-CoV-2 antibody immunoassays and a novel 384-well ELISA. We did a head-to-head assessment of SARS-CoV-2 IgG assay (Abbott, Chicago, IL, USA), LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy), Elecsys Anti-SARS-CoV-2 assay (Roche, Basel, Switzerland), SARS-CoV-2 Total assay (Siemens, Munich, Germany), and a novel 384-well ELISA (the Oxford immunoassay). We derived sensitivity and specificity from 976 pre-pandemic blood samples (collected between Sept 4, 2014, and Oct 4, 2016) and 536 blood samples from patients with laboratory-confirmed SARS-CoV-2 infection, collected at least 20 days post symptom onset (collected between Feb 1, 2020, and May 31, 2020). Receiver operating characteristic (ROC) curves were used to assess assay thresholds. At the manufacturers' thresholds, for the Abbott assay sensitivity was 92·7% (95% CI 90·2–94·8) and specificity was 99·9% (99·4–100%); for the DiaSorin assay sensitivity was 96·2% (94·2–97·7) and specificity was 98·9% (98·0–99·4); for the Oxford immunoassay sensitivity was 99·1% (97·8–99·7) and specificity was 99·0% (98·1–99·5); for the Roche assay sensitivity was 97·2% (95·4–98·4) and specificity was 99·8% (99·3–100); and for the Siemens assay sensitivity was 98·1% (96·6–99·1) and specificity was 99·9% (99·4–100%). All assays achieved a sensitivity of at least 98% with thresholds optimised to achieve a specificity of at least 98% on samples taken 30 days or more post symptom onset. Four commercial, widely available assays and a scalable 384-well ELISA can be used for SARS-CoV-2 serological testing to achieve sensitivity and specificity of at least 98%. The Siemens assay and Oxford immunoassay achieved these metrics without further optimisation. This benchmark study in immunoassay assessment should enable refinements of testing strategies and the best use of serological testing resource to benefit individuals and population health. Public Health England and UK National Institute for Health Research.

The 2022 Monkeypox virus (MPXV) global outbreak boosted development of multiple serological assays to aid understanding of Mpox immunology. The study aimed to assess a multiplexed solid-phase electrochemiluminescence immunoassay (Meso Scale Discovery (MSD)) for simultaneous detection of antibodies against MPXV, including A35, E8 and M1 antigens, along with corresponding Vaccina Virus (VACV) homologues and demonstrate its accuracy in assessing antibody titres post-vaccination and infection. Assay performance was assessed for simultaneous detection of antibodies against MPXV and corresponding VACV antigens. Sensitivity and specificity were evaluated with paediatric negatives (n = 215), pre- and post-IMVANEX vaccinated (n = 80), and MPXV (Clade IIb, n = 39) infected serum samples. The assay demonstrated high specificity (75.68 % (CI: 69.01–81.29) - 95.98 % (CI:92.54–97.87)) and sensitivity (62.11 % (CI:52.06–71.21) - 98.59 % (CI:92.44 %–99.93 %)) depending on the Orthopoxvirus antigen. Preferential binding was observed between MPXV-infected individuals and MPXV antigens, while vaccinated individuals exhibited increased binding to VACV antigens. These results highlight differential binding patterns between antigen homologues in related viruses. Overall, this assay demonstrates high sensitivities in detecting antibodies for multiple relevant MPXV and VACV antigens post-infection and post-vaccination, indicating its utility in understanding immune responses to Orthopoxviruses in current and future outbreaks and evaluating the immunogenicity of new-generation Mpox-specific vaccinations. •Simultaneous measurement of IgG to multiple MPXV and VACV homologous proteins•Sensitive and specific assay for detecting Orthopoxvirus antibodies•Detects Orthopoxvirus IgG antibodies in vaccinated sera 220 days after two doses•Mpox-infected individuals show preferential binding to MPXV over VACV antigens•Higher anti-MPXV A29 and anti-VACV A27 IgG titres post infection versus vaccination

In response to a national mpox (formerly known as monkeypox) outbreak in England, children exposed to a confirmed mpox case were offered modified vaccinia Ankara–Bavaria Nordic (MVA-BN), a third-generation smallpox vaccine, for post-exposure prophylaxis. We aimed to assess the safety and reactogenicity and humoral and cellular immune response, following the first reported use of MVA–BN in children. This is an assessment of children receiving MVA–BN for post-exposure prophylaxis in response to a national mpox outbreak in England. All children receiving MVA–BN were asked to complete a post-vaccination questionnaire online and provide a blood sample 1 month and 3 months after vaccination. Outcome measures for the questionnaire included reactogenicity and adverse events after vaccination. Blood samples were tested for humoural, cellular, and cytokine responses and compared with unvaccinated paediatric controls who had never been exposed to mpox. Between June 1 and Nov 30, 2022, 87 children had one MVA–BN dose and none developed any serious adverse events or developed mpox disease after vaccination. Post-vaccination reactogenicity questionnaires were completed by 45 (52%) of 87 children. Their median age was 5 years (IQR 5–9), 25 (56%) of 45 were male, and 22 (49%) of 45 were White. 16 (36%) reported no symptoms, 18 (40%) reported local reaction only, and 11 (24%) reported systemic symptoms with or without local reactions. Seven (8%) of 87 children provided a first blood sample a median of 6 weeks (IQR 6·0–6·5) after vaccination and five (6%) provided a second blood sample at a median of 15 weeks (14–15). All children had poxvirus IgG antibodies with titres well above the assay cutoff of OD450nm 0·1926 with mean absorbances of 1·380 at six weeks and 0·9826 at 15 weeks post-vaccination. Assessment of reactivity to 27 recombinant vaccina virus and monkeypox virus proteins showed humoral antigen recognition, primarily to monkeypox virus antigens B6, B2, and vaccina virus antigen B5, with waning of humoral responses observed between the two timepoints. All children had a robust T-cell response to whole modified vaccinia Ankara virus and a select pool of conserved pan-Poxviridae peptides. A balanced CD4+ and CD8+ T-cell response was evident at 6 weeks, which was retained at 15 weeks after vaccination. A single dose of MVA–BN for post-exposure prophylaxis was well-tolerated in children and induced robust antibody and cellular immune responses up to 15 weeks after vaccination. Larger studies are needed to fully assess the safety, immunogenicity, and effectiveness of MVA–BN in children. Our findings, however, support its on-going use to prevent mpox in children as part of an emergency public health response. UK Health Security Agency.

The purpose of this research study was to examine the perceived barriers female school superintendents experience starting with the hiring process, continuing through their tenure in the role and finally as they leave the superintendency. This research study was delivered to 1,846 school superintendents with 245 participants completing the survey. Participants were asked varying demographic data and were additionally asked to rate their perceptions of barriers women face while pursuing a position, barriers experienced during their tenure, strategies in overcoming any barrier, and female’s risk of non-continuance in the superintendent role. A one-way ANOVA found no significant difference between position held immediately prior to superintendency and barriers experienced during tenure based on position held immediately prior to the superintendency. A separate one-way ANOVA found no significant difference between position held immediately prior to superintedency and risk of non-continuance based on position held immediately prior to the superintendency. A third one-way ANOVA found no significant difference between the number of years as superintendent and strategies in overcoming barriers based on number of years as superintendent. Finally, an independent samples t test found no significant difference between male and female superintendents on barriers perceived on female superintendent candidate experiences in their roles.

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East Hartford High School students began their activities early this year by presenting a musical comedy in August. The production, \"The Boyfriend,\" was sponsored by the East Hartford Fine Arts Committee and was held on Aug. 2 and 3.