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Rapid vaccine-induced population immunity is a key global strategy to control COVID-19. Vaccination programmes must maximise early impact, particularly with accelerated spread of new variants.1 Most vaccine platforms use a two-dose prime-boost approach to generate an immune response against the virus S1 spike protein, the titres of which correlate with functional virus neutralisation and increase with boosting.2,3 To enable larger numbers of people to receive the first dose, delayed administration of the second dose has been advocated and implemented by some.1 The impact of previous SARS-CoV-2 infection on the need for boosting is not known. To test this, we undertook a nested case-control analysis of 51 participants of COVIDsortium,4,5 an ongoing longitudinal observational study of health-care workers (HCWs) in London who underwent weekly PCR and quantitative serology testing from the day of the first UK lockdown on March 23, 2020, and for 16 weeks onwards. 24 of 51 HCWs had a previous laboratory-confirmed mild or asymptomatic SARS-CoV-2 infection, as confirmed by positive detection of antibodies against the SARS-CoV-2 nucleocapsid (Elecsys Anti-SARS-CoV-2 N ECLIA, Roche Diagnostics, Burgess Hill, UK) or the receptor binding domain of the SARS-CoV-2 S1 subunit of the spike protein (anti-S; Elecsys anti-SARS-CoV-2 spike ECLIA, Roche Diagnostics), whereas 27 HCWs remained seronegative.

Among the unknowns in decoding the pathogenesis of SARS-CoV-2 persistent symptoms in Long Covid is whether there is a contributory role of abnormal immunity during acute infection. It has been proposed that Long Covid is a consequence of either an excessive or inadequate initial immune response. Here, we analyze SARS-CoV-2 humoral and cellular immunity in 86 healthcare workers with laboratory confirmed mild or asymptomatic SARS-CoV-2 infection during the first wave. Symptom questionnaires allow stratification into those with persistent symptoms and those without for comparison. During the period up to 18-weeks post-infection, we observe no difference in antibody responses to spike RBD or nucleoprotein, virus neutralization, or T cell responses. Also, there is no difference in the profile of antibody waning. Analysis at 1-year, after two vaccine doses, comparing those with persistent symptoms to those without, again shows similar SARS-CoV-2 immunity. Thus, quantitative differences in these measured parameters of SARS-CoV-2 adaptive immunity following mild or asymptomatic acute infection are unlikely to have contributed to Long Covid causality. ClinicalTrials.gov (NCT04318314). Authors utilise a cohort of healthcare workers, infected during the first wave of the SARS-CoV-2 pandemic, to assess symptom persistence and humoral and cellular immunity.

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.

Mpox is an ongoing threat to international health security requiring ongoing research. Antibody tests are needed for surveillance studies to understand clinical and sub-clinical transmission risks and respond to outbreaks. With the objective of having a simple and low-cost antibody platform, we developed a laboratory ELISA kit combining four immunodominant mpox proteins to quantify mpox IgG antibody concentration and determine serostatus. The combined assay returns one data point (mpox IgG ratio) per sample. UK serum samples from individuals' post-infection, post-vaccination and those with no known history of mpox infection or vaccination were used to evaluate the assay. The assay effectively discriminated individuals with prior infection or vaccination combined from those without (AUC ·98 [95% CI ·95-1·00], < .0001), returning a sensitivity and specificity of 95% (95% CI 86·71-98·68 and 89·92-97·78%, respectively). Findings highlight the potential of the ELISA as an accurate and practical solution to aid access to mpox immunodiagnostics and should be evaluated further in endemic settings.

Precision monitoring of antibody responses during the COVID-19 pandemic is increasingly important during large scale vaccine rollout and rise in prevalence of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2) variants of concern (VOC). Equally important is defining Correlates of Protection (CoP) for SARS-CoV-2 infection and COVID-19 disease. Data from epidemiological studies and vaccine trials identified virus neutralising antibodies (Nab) and SARS-CoV-2 antigen-specific (notably RBD and S) binding antibodies as candidate CoP. In this study, we used the World Health Organisation (WHO) international standard to benchmark neutralising antibody responses and a large panel of binding antibody assays to compare convalescent sera obtained from: a) COVID-19 patients; b) SARS-CoV-2 seropositive healthcare workers (HCW) and c) seronegative HCW. The ultimate aim of this study is to identify biomarkers of humoral immunity that could be used to differentiate severe from mild or asymptomatic SARS-CoV-2 infections. Some of these biomarkers could be used to define CoP in further serological studies using samples from vaccination breakthrough and/or re-infection cases. Whenever suitable, the antibody levels of the samples studied were expressed in International Units (IU) for virus neutralisation assays or in Binding Antibody Units (BAU) for ELISA tests. In this work we used commercial and non-commercial antibody binding assays; a lateral flow test for detection of SARS-CoV-2-specific IgG/IgM; a high throughput multiplexed particle flow cytometry assay for SARS-CoV-2 Spike (S), Nucleocapsid (N) and Receptor Binding Domain (RBD) proteins); a multiplex antigen semi-automated immuno-blotting assay measuring IgM, IgA and IgG; a pseudotyped microneutralisation test (pMN) and an electroporation-dependent neutralisation assay (EDNA). Our results indicate that overall, severe COVID-19 patients showed statistically significantly higher levels of SARS-CoV-2-specific neutralising antibodies (average 1029 IU/ml) than those observed in seropositive HCW with mild or asymptomatic infections (379 IU/ml) and that clinical severity scoring, based on WHO guidelines was tightly correlated with neutralisation and RBD/S antibodies. In addition, there was a positive correlation between severity, N-antibody assays and intracellular virus neutralisation.

Among more than 35,000 health care workers, those who received two doses of BNT162b2 vaccine had a high level of protection against Covid-19, regardless of the between-dose interval, but efficacy began to wane after 6 months. Immunity in vaccinated, previously infected persons was more effective and durable (>1 year) than that in vaccinated persons who had not been infected.

[...]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

Abstract Mpox in humans is a rash illness resulting from infection with monkeypox virus (MPXV). In 2022, a public health emergency of international concern (PHEIC) was declared with 115 countries reporting cases of Mpox. Most of these countries had not previously reported cases. This global outbreak was sustained primarily by human-to-human transmission within complex sexual networks. Whilst these cases were similar to previous clade II West African MPXV isolates, they were sufficiently genomically distinct to result in WHO recognizing two subclades within clade II: clade IIa and clade IIb. In 2024, a second PHEIC was declared, resulting from a marked increase in cases of clade I MPXV. In this scoping review, we compare the major clinical, epidemiological, and genomic features of the major mpox lineages and the implications for vaccination, transmission, infection control and treatment.. A scoping review, comparing the major clinical, epidemiological, and genomic features of clades I, IIa, and IIb MPXV.

Serological correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after vaccination (“vaccine breakthrough”) have been described. However, T cell correlates of protection against breakthrough are incompletely defined, especially the specific contributions of CD4+ and CD8+ T cells. Here, 279 volunteers in the Protective Immunity from T Cells in Healthcare Workers (PITCH) UK cohort study were enrolled in a nested case-control study. Cases were those who tested SARS-CoV-2 PCR or lateral flow device (LFD) positive after two vaccine doses during the Delta-predominant era ( n = 32), while controls were those who did not report a positive test or undergo anti-nucleocapsid immunoglobulin G (IgG) seroconversion during this period ( n = 247). Previous SARS-CoV-2 infection prior to vaccination was associated with reduced odds of vaccine breakthrough. Using samples from 28 d after the second vaccine dose, before all breakthroughs occurred, we observed future cases had lower ancestral spike (S)- and receptor binding domain-specific IgG titers and S1- and S2-specific T cell interferon gamma (IFNγ) responses compared with controls, although these differences did not persist when individuals were stratified according to previous infection status before vaccination. In a subset of matched infection-naïve cases and controls, vaccine breakthrough cases had lower CD4+ and CD8+ IFNγ and tumor necrosis factor (TNF) responses to Delta S peptides compared with controls. For CD8+ responses, this difference appeared to be driven by reduced responses to Delta compared with ancestral peptides among cases; this reduced response to Delta peptides was not observed in controls. Our findings support a protective role for T cells against Delta breakthrough infection. Defining correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infection informs vaccine policy for booster doses and future vaccine designs. Existing studies demonstrate humoral correlates of protection, but the role of T cells in protection is still unclear. In this study, we explore antibody and T cell immune responses associated with protection against Delta variant vaccine breakthrough infection in a well-characterized cohort of UK Healthcare Workers (HCWs). We demonstrate evidence to support a role for CD4+ and CD8+ T cells as well as antibodies against Delta vaccine breakthrough infection. In addition, our results suggest a potential role for cross-reactive T cells in vaccine breakthrough.

Understanding secondary attack rates is a key knowledge gap in the ongoing clade Ib mpox virus (MPXV) outbreak in the Democratic Republic of the Congo. Here, we report the first cross-sectional serological study to investigate local MPXV clade Ib transmission in South Kivu, DRC. Seropositivity was defined as a detectable titer in a cell lysate-based screening ELISA and confirmation by virus neutralization test. Sera were collected in November and December 2023 ( n  = 120), and in May 2024 ( n  = 48) from professional sex workers (PSW) and visitors of 25 bars with reports of mpox cases. We detected serological evidence for MPXV infection in 18% and 17% of these sera, respectively, indicating that PSW played an important role in MPXV clade Ib transmission in this region. Additionally, sera from 108 direct contacts of mpox cases from 34 households were collected between September 2023 and May 2024. Serological evidence for MPXV infection was found in at least one serum sample in 50% of households, including in nine households with seropositive minors, providing evidence for close-contact household transmission. Serological studies are needed to comprehend the extent and severity of the ongoing MPXV outbreak, and may be used to guide targeted vaccination strategies, particularly for high-risk groups. Serological studies are needed to understand the ongoing clade Ib mpox outbreak in the Democratic Republic of the Congo and neighboring countries. Here, the authors conduct a cross-sectional serological study in South Kivu, highlighting the role of professional sex workers and household transmission in mpox epidemiology.