Pub Date : 2024-02-12DOI: 10.1101/2024.02.08.24302502
Daniel A Stocks, Amy C Thomas, Adam Finn, Leon Danon, Ellen Brooks-Pollock
Introduction: Future COVID-19 vaccine programmes need to take into account the variable responses elicited by different vaccines and their waning protection over time. Existing descriptions of antibody response to COVID-19 vaccination convey limited information about the mechanisms of antibody production and maintenance. Methods: We describe the antibody dynamics elicited by COVID-19 vaccination with two biologically-motivated mathematical models of antibody production by plasma cells and subsequent decay. We fit the models using Markov Chain Monte Carlo to seroprevalence data from 14,602 uninfected individuals collected via the primary care network in England between May 2020 and September 2022. We ensure our models are structurally and practically identifiable when using anti- body data alone. We analyse the effect of age, vaccine type, number of doses, and the interval between doses on antibody production and longevity of response. Results: We find evidence that individuals over 35 years of age who received a second dose of ChAdOx1-S generate a persistent antibody response suggestive of long-lived plasma cell induction, while individuals that receive two doses of BNT162b2, or one dose of either vaccine do not. We also find that plasamblast productive capacity, the likely driver of short-term antibody responses, is greater in younger people than older people (≤ 4.5 fold change in point estimates), people vaccinated with two doses than people vaccinated with one dose (≤ 12 fold change), and people vaccinated with BNT162b2 than people vaccinated with ChAdOx1-S (≤ 440 fold change). The effect of age on antibody dynamics is more pronounced in people vaccinated with BNT162b2 than people vaccinated with ChAdOx1-S. We find the half-life of an antibody to be between 23 - 106 days. Conclusion: Routinely-collected seroprevalence data are a valuable source of information for characterising within-host mechanisms of antibody production and persistence. Extended sampling and linking seroprevalence data to outcomes would allow for powerful conclusions about how humoral kinetics protect against disease.
{"title":"Mechanistic models of humoral kinetics following COVID-19 vaccination","authors":"Daniel A Stocks, Amy C Thomas, Adam Finn, Leon Danon, Ellen Brooks-Pollock","doi":"10.1101/2024.02.08.24302502","DOIUrl":"https://doi.org/10.1101/2024.02.08.24302502","url":null,"abstract":"Introduction: Future COVID-19 vaccine programmes need to take into account the variable responses elicited by different vaccines and their waning protection\u0000over time. Existing descriptions of antibody response to COVID-19 vaccination convey limited information about the mechanisms of antibody production and\u0000maintenance. Methods: We describe the antibody dynamics elicited by COVID-19 vaccination with two biologically-motivated mathematical models of antibody production by\u0000plasma cells and subsequent decay. We fit the models using Markov Chain Monte Carlo to seroprevalence data from 14,602 uninfected individuals collected via the\u0000primary care network in England between May 2020 and September 2022. We ensure our models are structurally and practically identifiable when using anti-\u0000body data alone. We analyse the effect of age, vaccine type, number of doses, and the interval between doses on antibody production and longevity of response.\u0000Results: We find evidence that individuals over 35 years of age who received a second dose of ChAdOx1-S generate a persistent antibody response suggestive of long-lived plasma cell induction, while individuals that receive two doses of BNT162b2, or one dose of either vaccine do not. We also find that plasamblast\u0000productive capacity, the likely driver of short-term antibody responses, is greater in younger people than older people (≤ 4.5 fold change in point estimates), people vaccinated with two doses than people vaccinated with one dose (≤ 12 fold change), and people vaccinated with BNT162b2 than people vaccinated with ChAdOx1-S (≤ 440 fold change). The effect of age on antibody dynamics is more pronounced in people vaccinated with BNT162b2 than people vaccinated with\u0000ChAdOx1-S. We find the half-life of an antibody to be between 23 - 106 days. Conclusion: Routinely-collected seroprevalence data are a valuable source of information for characterising within-host mechanisms of antibody production and persistence. Extended sampling and linking seroprevalence data to outcomes would allow for powerful conclusions about how humoral kinetics protect against disease.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139758951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-08DOI: 10.1101/2024.02.07.24302472
Fatema Al-Rashed, Halemah AlSaeed, Nourah Almansour, Fahd Al- Mulla, Yusuf A. Hannun, Rasheed Ahmad
Background Atherosclerosis epitomizes a multifaceted cardiovascular disorder, predominantly characterized by the accumulation of cholesterol-laden plaques within arterial walls. Despite substantial research, the precise mechanisms governing the formation of these cholesterol-rich plaques remain partially elucidated. This study delves into the complex interplay of interleukin-6 (IL-6) receptors, shedding light on their pivotal role in orchestrating cholesterol homeostasis in human macrophages.
{"title":"IL-6R (trans-signaling) is a key regulator of reverse cholesterol transport in lipid-laden macrophages","authors":"Fatema Al-Rashed, Halemah AlSaeed, Nourah Almansour, Fahd Al- Mulla, Yusuf A. Hannun, Rasheed Ahmad","doi":"10.1101/2024.02.07.24302472","DOIUrl":"https://doi.org/10.1101/2024.02.07.24302472","url":null,"abstract":"<strong>Background</strong> Atherosclerosis epitomizes a multifaceted cardiovascular disorder, predominantly characterized by the accumulation of cholesterol-laden plaques within arterial walls. Despite substantial research, the precise mechanisms governing the formation of these cholesterol-rich plaques remain partially elucidated. This study delves into the complex interplay of interleukin-6 (IL-6) receptors, shedding light on their pivotal role in orchestrating cholesterol homeostasis in human macrophages.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139758590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-06DOI: 10.1101/2024.02.06.24302345
Chapin Stephen Korosec, David W Dick, Iain Moyles, James Watmough
SARS-CoV-2 lipid nanoparticle mRNA therapeutics continue to be administered as the predominant therapeutic intervention to reduce COVID-19 disease pathogenesis. Quantifying the kinetics of the secondary immune response from subsequent doses beyond the primary series, and understanding how dose-dependent immune waning kinetics vary as a function of age, sex, and various comorbidities, remains an important question. We study anti-spike IgG waning kinetics in 152 individuals who received an mRNA-based primary series and a subset of 137 individuals who then received a booster dose. We find the booster dose elicits a 71-84% increase in the median Anti-S half life over that of the primary series. We find the Anti-S half life for both primary series and booster doses drops as a function of increased year of age. However, we stress that although chronological age continues to be a good proxy for vaccine-induced humoral waning, immunosenescence is likely not the mechanism, rather, more likely the mechanism is related to the presence of noncommunicable diseases, which also accumulate with age, that affect immune regulation. We are able to independently reproduce recent observations that those with pre-existing asthma exhibit a stronger primary series humoral response to vaccination than compared to those that do not, and further find this result is sustained for the booster dose. Finally, via a single-variate Kruskal-Wallis Test we find no difference between male and female decay kinetics, however, a multivariate approach utilizing Lasso regression for feature selection reveals a statistically significant (p-value <10-3), albeit small, bias in favour of longer-lasting humoral immunity amongst males.
{"title":"SARS-CoV-2 booster vaccine dose significantly extends humoral immune response half-life beyond the primary series","authors":"Chapin Stephen Korosec, David W Dick, Iain Moyles, James Watmough","doi":"10.1101/2024.02.06.24302345","DOIUrl":"https://doi.org/10.1101/2024.02.06.24302345","url":null,"abstract":"SARS-CoV-2 lipid nanoparticle mRNA therapeutics continue to be administered as the predominant therapeutic intervention to reduce COVID-19 disease pathogenesis. Quantifying the kinetics of the secondary immune response from subsequent doses beyond the primary series, and understanding how dose-dependent immune waning kinetics vary as a function of age, sex, and various comorbidities, remains an important question. We study anti-spike IgG waning kinetics in 152 individuals who received an mRNA-based primary series and a subset of 137 individuals who then received a booster dose. We find the booster dose elicits a 71-84% increase in the median Anti-S half life over that of the primary series. We find the Anti-S half life for both primary series and booster doses drops as a function of increased year of age. However, we stress that although chronological age continues to be a good proxy for vaccine-induced humoral waning, immunosenescence is likely not the mechanism, rather, more likely the mechanism is related to the presence of noncommunicable diseases, which also accumulate with age, that affect immune regulation. We are able to independently reproduce recent observations that those with pre-existing asthma exhibit a stronger primary series humoral response to vaccination than compared to those that do not, and further find this result is sustained for the booster dose. Finally, via a single-variate Kruskal-Wallis Test we find no difference between male and female decay kinetics, however, a multivariate approach utilizing Lasso regression for feature selection reveals a statistically significant (p-value <10<sup>-3</sup>), albeit small, bias in favour of longer-lasting humoral immunity amongst males.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"158 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139758864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-06DOI: 10.1101/2024.02.02.24302068
Sarah Djeddi, Daniela Fermandez-Salinas, George Huang, Vitor Aguiar, Chitrasen Mohanty, Christina Kendziorski, Steven Gazal, Joshua Boyce, Carole Ober, James Gern, Nora Barrett, Maria Gutierrez-Arcelus
Asthma is a complex disease caused by genetic and environmental factors. Epidemiological studies have shown that in children, wheezing during rhinovirus infection (a cause of the common cold) is associated with asthma development during childhood. This has led scientists to hypothesize there could be a causal relationship between rhinovirus infection and asthma or that RV-induced wheezing identifies individuals at increased risk for asthma development. However, not all children who wheeze when they have a cold develop asthma. Genome-wide association studies (GWAS) have identified hundreds of genetic variants contributing to asthma susceptibility, with the vast majority of likely causal variants being non-coding. Integrative analyses with transcriptomic and epigenomic datasets have indicated that T cells drive asthma risk, which has been supported by mouse studies. However, the datasets ascertained in these integrative analyses lack airway epithelial cells. Furthermore, large-scale transcriptomic T cell studies have not identified the regulatory effects of most non-coding risk variants in asthma GWAS, indicating there could be additional cell types harboring these 'missing regulatory effects'. Given that airway epithelial cells are the first line of defense against rhinovirus, we hypothesized they could be mediators of genetic susceptibility to asthma. Here we integrate GWAS data with transcriptomic datasets of airway epithelial cells subject to stimuli that could induce activation states relevant to asthma. We demonstrate that epithelial cultures infected with rhinovirus significantly upregulate childhood-onset asthma-associated genes. We show that this upregulation occurs specifically in non-ciliated epithelial cells. This enrichment for genes in asthma risk loci, or 'asthma heritability enrichment' is also significant for epithelial genes upregulated with influenza infection, but not with SARS-CoV-2 infection or cytokine activation. Additionally, cells from patients with asthma showed a stronger heritability enrichment compared to cells from healthy individuals. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.
{"title":"Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic susceptibility to childhood-onset asthma","authors":"Sarah Djeddi, Daniela Fermandez-Salinas, George Huang, Vitor Aguiar, Chitrasen Mohanty, Christina Kendziorski, Steven Gazal, Joshua Boyce, Carole Ober, James Gern, Nora Barrett, Maria Gutierrez-Arcelus","doi":"10.1101/2024.02.02.24302068","DOIUrl":"https://doi.org/10.1101/2024.02.02.24302068","url":null,"abstract":"Asthma is a complex disease caused by genetic and environmental factors. Epidemiological studies have shown that in children, wheezing during rhinovirus infection (a cause of the common cold) is associated with asthma development during childhood. This has led scientists to hypothesize there could be a causal relationship between rhinovirus infection and asthma or that RV-induced wheezing identifies individuals at increased risk for asthma development. However, not all children who wheeze when they have a cold develop asthma. Genome-wide association studies (GWAS) have identified hundreds of genetic variants contributing to asthma susceptibility, with the vast majority of likely causal variants being non-coding. Integrative analyses with transcriptomic and epigenomic datasets have indicated that T cells drive asthma risk, which has been supported by mouse studies. However, the datasets ascertained in these integrative analyses lack airway epithelial cells. Furthermore, large-scale transcriptomic T cell studies have not identified the regulatory effects of most non-coding risk variants in asthma GWAS, indicating there could be additional cell types harboring these 'missing regulatory effects'. Given that airway epithelial cells are the first line of defense against rhinovirus, we hypothesized they could be mediators of genetic susceptibility to asthma. Here we integrate GWAS data with transcriptomic datasets of airway epithelial cells subject to stimuli that could induce activation states relevant to asthma. We demonstrate that epithelial cultures infected with rhinovirus significantly upregulate childhood-onset asthma-associated genes. We show that this upregulation occurs specifically in non-ciliated epithelial cells. This enrichment for genes in asthma risk loci, or 'asthma heritability enrichment' is also significant for epithelial genes upregulated with influenza infection, but not with SARS-CoV-2 infection or cytokine activation. Additionally, cells from patients with asthma showed a stronger heritability enrichment compared to cells from healthy individuals. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139758583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-31DOI: 10.1101/2024.01.30.24302017
Abdul Rehman Haris, Furqan Maqsood, Hamid Nawaz Tipu, Dawood Ahmad
Background HLA-B27 is a class I MHC protein that is associated with different diseases collectively called, spondyloarthropathies. It includes; 2. Ankylosing spondylitis, which causes inflammation of the bones in your spine 3. Reactive arthritis, which causes inflammation of your joints, urethra, and eyes, and in some cases lesions on your skin 4. Juvenile rheumatoid arthritis 5. Anterior Uveitis, which causes swelling and irritation in the middle layer of your eye Objectives To determine the prevalence of HLA-B27 in patients with backache at the Armed Forces Institute of Pathology in Rawalpindi. This descriptive cross-sectional study was conducted between June 2020 and Nov 2020. Material and methods Of the 243 patients, 167 males and 76 females were tested for HLA-B27 during the study period. Venous blood samples (3 mL) were collected in EDTA tubes and processed for HLA-B27 gene identification on the cell surface. A two-color flow cytometry panel was used to analyze samples using a BD FACS Canto II flow cytometer on BD FACS Diva software. The dot plot was created using an isotype control in four quadrants, and positive and negative populations of cells were identified. Results A total of 243 patients were analyzed for the presence of HLA-B27 using flow cytometry. Of the 243 patients, 167 were male and 76 were female patient.51 male patients tested positive, with a positivity rate of 30.53% among the male population and 20.98% among the general population. In contrast to the male population, 12 female patients tested positive for the HLA-B27 gene, with a positivity rate of 15.78% among the female population and 4.93% among the general population. The total positivity rate was 25.92%, with a higher prevalence in the male population included in this study. Conclusion All individuals tested for HLA B27 were included in this study. This study showed that positivity rate of HLA-B27 is more in males with a percentage of 20.98% as compared to female population (4.93%).
{"title":"Determination of prevalence of HLA-B27 in patients with backache at Armed Forces Institute of Pathology (AFIP), Rawalpindi","authors":"Abdul Rehman Haris, Furqan Maqsood, Hamid Nawaz Tipu, Dawood Ahmad","doi":"10.1101/2024.01.30.24302017","DOIUrl":"https://doi.org/10.1101/2024.01.30.24302017","url":null,"abstract":"Background\u0000HLA-B27 is a class I MHC protein that is associated with different diseases collectively called, spondyloarthropathies. It includes;\u00002.\tAnkylosing spondylitis, which causes inflammation of the bones in your spine 3.\tReactive arthritis, which causes inflammation of your joints, urethra, and eyes, and in some cases lesions on your skin\u00004.\tJuvenile rheumatoid arthritis\u00005.\tAnterior Uveitis, which causes swelling and irritation in the middle layer of your eye\u0000Objectives\u0000To determine the prevalence of HLA-B27 in patients with backache at the Armed Forces Institute of Pathology in Rawalpindi. This descriptive cross-sectional study was conducted between June 2020 and Nov 2020.\u0000Material and methods\u0000Of the 243 patients, 167 males and 76 females were tested for HLA-B27 during the study period. Venous blood samples (3 mL) were collected in EDTA tubes and processed for HLA-B27 gene identification on the cell surface. A two-color flow cytometry panel was used to analyze samples using a BD FACS Canto II flow cytometer on BD FACS Diva software. The dot plot was created using an isotype control in four quadrants, and positive and negative populations of cells were identified.\u0000Results\u0000A total of 243 patients were analyzed for the presence of HLA-B27 using flow cytometry. Of the 243 patients, 167 were male and 76 were female patient.51 male patients tested positive, with a positivity rate of 30.53% among the male population and 20.98% among the general population. In contrast to the male population, 12 female patients tested positive for the HLA-B27 gene, with a positivity rate of 15.78% among the female population and 4.93% among the general population. The total positivity rate was 25.92%, with a higher prevalence in the male population included in this study.\u0000Conclusion\u0000All individuals tested for HLA B27 were included in this study. This study showed that positivity rate of HLA-B27 is more in males with a percentage of 20.98% as compared to female population (4.93%).","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139657753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-30DOI: 10.1101/2024.01.29.24301962
Patrick K Gleeson, Knashawn H Morales, Timothy M Buckey, Olajumoke O Fadugba, Andrea J Apter, Jason D Christie, Blanca E Himes
BACKGROUND: Aeroallergen testing can improve precision care for persistent asthma and is recommended by the U.S. clinical guidelines. How testing benefits diverse populations of adults with asthma, and the importance of the testing modality used, are not fully understood. OBJECTIVE: We sought to evaluate whether receipt of aeroallergen testing was associated with a reduction in oral corticosteroid (OCS) bursts. METHODS: We used electronic health record data to conduct a retrospective, observational cohort study of adults with asthma who were prescribed an inhaled corticosteroid and had an Allergy/Immunology visit in a large health system between 1/1/2017-6/30/2022. Negative binomial regression models were used to evaluate whether OCS bursts in the 12-month period after an initial visit were reduced for patients who received aeroallergen testing. We also measured differences in benefit after excluding patients with chronic obstructive pulmonary disease (COPD) and smoking histories, and whether testing receipt was via skin prick or serum. RESULTS: 668/1,383 (48.3%) patients received testing. Receipt of testing was not associated with fewer bursts in all patients (incidence rate ratio (IRR)=0.83 versus no testing, p=0.059), but it was among never smokers without COPD (417/844 tested, IRR=0.68, p=0.004). The receipt of skin testing was associated with fewer bursts in all patients (418/1,383 tested, IRR=0.77, p=0.02) and among never smokers without COPD (283/844 tested, IRR=0.59 versus no testing, p=0.001). CONCLUSION: Guideline-concordant aeroallergen testing in the context of Allergy/Immunology care was associated with clinical benefit in a real-life, diverse cohort of adults with asthma. This benefit varied according to patient comorbidities and the testing modality.
{"title":"Benefits of Aeroallergen Testing on Oral Corticosteroid Bursts in Adults with Asthma","authors":"Patrick K Gleeson, Knashawn H Morales, Timothy M Buckey, Olajumoke O Fadugba, Andrea J Apter, Jason D Christie, Blanca E Himes","doi":"10.1101/2024.01.29.24301962","DOIUrl":"https://doi.org/10.1101/2024.01.29.24301962","url":null,"abstract":"BACKGROUND: Aeroallergen testing can improve precision care for persistent asthma and is recommended by the U.S. clinical guidelines. How testing benefits diverse populations of adults with asthma, and the importance of the testing modality used, are not fully understood. OBJECTIVE: We sought to evaluate whether receipt of aeroallergen testing was associated with a reduction in oral corticosteroid (OCS) bursts.\u0000METHODS: We used electronic health record data to conduct a retrospective, observational cohort study of adults with asthma who were prescribed an inhaled corticosteroid and had an Allergy/Immunology visit in a large health system between 1/1/2017-6/30/2022. Negative binomial regression models were used to evaluate whether OCS bursts in the 12-month period after an initial visit were reduced for patients who received aeroallergen testing. We also measured differences in benefit after excluding patients with chronic obstructive pulmonary disease (COPD) and smoking histories, and whether testing receipt was via skin prick or serum. RESULTS: 668/1,383 (48.3%) patients received testing. Receipt of testing was not associated with fewer bursts in all patients (incidence rate ratio (IRR)=0.83 versus no testing, p=0.059), but it was among never smokers without COPD (417/844 tested, IRR=0.68, p=0.004). The receipt of skin testing was associated with fewer bursts in all patients (418/1,383 tested, IRR=0.77, p=0.02) and among never smokers without COPD (283/844 tested, IRR=0.59 versus no testing, p=0.001). CONCLUSION: Guideline-concordant aeroallergen testing in the context of Allergy/Immunology care was associated with clinical benefit in a real-life, diverse cohort of adults with asthma. This benefit varied according to patient comorbidities and the testing modality.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139585854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-29DOI: 10.1101/2024.01.28.24301893
Aaron L Oom, Angelica C Kottkamp, Kesi K Wilson, Miilani Yonatan, Stephanie Rettig, Heekoung Allison Youn, Michael Tuen, Yusra Shah, Ashley L DuMont, Marie I Samanovic, Ralf Duerr, Mark J Mulligan, NYC OSMI Study Group
The 2022 global outbreak of clade IIb mpox was the first major outbreak of mpox outside of African nations. To control the outbreak, vaccination campaigns were begun using the third-generation orthopoxvirus vaccine MVA-BN. During the vaccination campaign, we launched the New York City Observational Study of Mpox Immunity (NYC OSMI). NYC OSMI is a longitudinal study that enrolled 171 MVA-BN vaccinees with or without prior smallpox vaccination and mpox convalescent individuals. Study participants had blood drawn prior to vaccination, after one dose, and after two doses. Mpox virus (MPXV) neutralizing titers in sera reach a comparable peak in naïve and experienced vaccinees. However, neutralizing titers return to baseline in less than one year for naïve individuals, while remaining elevated in those with prior smallpox vaccination. Both naïve and experienced individuals generate robust, immunodominant IgG responses against MPXV H3 and A35, but with significantly lower avidity in naïve vaccinees. Their vaccinia virus homologs H3 and A33 have previously been shown to be protective targets for orthopoxvirus infection and disease in mouse models. These data highlight a low avidity antibody response elicited by MVA-BN that is short-lived in naïve vaccinees. This study supports the need for studies of long-term protection from MVA-BN, the potential need for booster doses, and further development of next-generation orthopoxvirus vaccines.
{"title":"The Durability and Avidity of MPXV-specific Antibodies Induced by the Two-dose MVA-BN Mpox Vaccine","authors":"Aaron L Oom, Angelica C Kottkamp, Kesi K Wilson, Miilani Yonatan, Stephanie Rettig, Heekoung Allison Youn, Michael Tuen, Yusra Shah, Ashley L DuMont, Marie I Samanovic, Ralf Duerr, Mark J Mulligan, NYC OSMI Study Group","doi":"10.1101/2024.01.28.24301893","DOIUrl":"https://doi.org/10.1101/2024.01.28.24301893","url":null,"abstract":"The 2022 global outbreak of clade IIb mpox was the first major outbreak of mpox outside of African nations. To control the outbreak, vaccination campaigns were begun using the third-generation orthopoxvirus vaccine MVA-BN. During the vaccination campaign, we launched the New York City Observational Study of Mpox Immunity (NYC OSMI). NYC OSMI is a longitudinal study that enrolled 171 MVA-BN vaccinees with or without prior smallpox vaccination and mpox convalescent individuals. Study participants had blood drawn prior to vaccination, after one dose, and after two doses. Mpox virus (MPXV) neutralizing titers in sera reach a comparable peak in naïve and experienced vaccinees. However, neutralizing titers return to baseline in less than one year for naïve individuals, while remaining elevated in those with prior smallpox vaccination. Both naïve and experienced individuals generate robust, immunodominant IgG responses against MPXV H3 and A35, but with significantly lower avidity in naïve vaccinees. Their vaccinia virus homologs H3 and A33 have previously been shown to be protective targets for orthopoxvirus infection and disease in mouse models. These data highlight a low avidity antibody response elicited by MVA-BN that is short-lived in naïve vaccinees. This study supports the need for studies of long-term protection from MVA-BN, the potential need for booster doses, and further development of next-generation orthopoxvirus vaccines.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139585900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Since the onset of the global pandemic caused by the emergence and spread of SARS-CoV-2 in early 2020, numerous studies have been conducted worldwide to understand our immune response to the virus. This study investigates the humoral response elicited by vaccination and by SARS-CoV-2 infection in the poorly studied food and retail workers in the Quebec City area. The 1.5-year study period spans from early 2021, when vaccination became available in this region, to mid-2022, following waves of virulence due to the emergence of the first Omicron variants. Cross-correlated with data on workplace protective measures, pre-existing conditions, activities and other potentially relevant factors, this longitudinal study applies recently developed ELISA data transformation to our dataset to obtain normal distribution. This unlocked the possibility to use the ANOVA-Welsh method for statistical analysis to obtain a statistical perspective of the serological response. Our work allows the identification of factors contributing to statistically relevant differences in the humoral response of the cohort and strengthens the utility of the use of decentralized approaches to serological analysis.
{"title":"Longitudinal Study on Seroprevalence and Immune Response to SARS-CoV-2 in a Population of Food and Retail Workers Through Transformation of ELISA Datasets","authors":"Abdelhadi Djaïleb, Megan-Faye Parker, Étienne Lavallée, Matthew Stuible, Yves Durocher, Mathieu Thériault, Kim Santerre, Caroline Gilbert, Denis Boudreau, Mariana Baz, Jean-Francois Masson, Marc-André Langlois, Sylvie Trottier, Daniela Quaglia, Joelle N. Pelletier","doi":"10.1101/2024.01.27.24301877","DOIUrl":"https://doi.org/10.1101/2024.01.27.24301877","url":null,"abstract":"Since the onset of the global pandemic caused by the emergence and spread of SARS-CoV-2 in early 2020, numerous studies have been conducted worldwide to understand our immune response to the virus. This study investigates the humoral response elicited by vaccination and by SARS-CoV-2 infection in the poorly studied food and retail workers in the Quebec City area. The 1.5-year study period spans from early 2021, when vaccination became available in this region, to mid-2022, following waves of virulence due to the emergence of the first Omicron variants. Cross-correlated with data on workplace protective measures, pre-existing conditions, activities and other potentially relevant factors, this longitudinal study applies recently developed ELISA data transformation to our dataset to obtain normal distribution. This unlocked the possibility to use the ANOVA-Welsh method for statistical analysis to obtain a statistical perspective of the serological response. Our work allows the identification of factors contributing to statistically relevant differences in the humoral response of the cohort and strengthens the utility of the use of decentralized approaches to serological analysis.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139585733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-28DOI: 10.1101/2024.01.26.24301725
Daniel Bertin, Pierre Bongrand, Nathalie Bardin
The success of artificial intelligence and machine learning is an incentive to develop new algorithms to increase the rapidity and reliability of medical diagnosis. Here we compared different strategies aimed at processing microscope images used to detect anti-neutrophil cytoplasmic antibodies, an important vasculitis marker: (i) basic classifier methods (logistic regression, k-nearest neighbors and decision tree) were used to process custom-made indices derived from immunofluorescence images yielded by 137 sera. (ii) These methods were combined with dimensional reduction to analyze 1733 individual cell images. iii) More complex models based on neural networks were used to analyze the same dataset. The efficiency of discriminating between positive and negative samples and different fluorescence patterns was quantified with Rand-type accuracy index, kappa index and ROC curve. It is concluded that basic models trained on a limited dataset allowed positive/negative discrimination with an efficiency comparable to that obtained by conventional analysis performed by humans (0.84 kappa score). More extensive datasets may be required for efficient discrimination between different fluorescence patterns generated by different auto-antibody species.
{"title":"Comparison of the capacity of several machine learning tools to assist immunofluorescence-based detection of anti-neutrophil cytoplasmic antibodies","authors":"Daniel Bertin, Pierre Bongrand, Nathalie Bardin","doi":"10.1101/2024.01.26.24301725","DOIUrl":"https://doi.org/10.1101/2024.01.26.24301725","url":null,"abstract":"The success of artificial intelligence and machine learning is an incentive to develop new\u0000algorithms to increase the rapidity and reliability of medical diagnosis. Here we compared different\u0000strategies aimed at processing microscope images used to detect anti-neutrophil cytoplasmic antibodies,\u0000an important vasculitis marker: (i) basic classifier methods (logistic regression, k-nearest neighbors and\u0000decision tree) were used to process custom-made indices derived from immunofluorescence images\u0000yielded by 137 sera. (ii) These methods were combined with dimensional reduction to analyze 1733\u0000individual cell images. iii) More complex models based on neural networks were used to analyze the\u0000same dataset. The efficiency of discriminating between positive and negative samples and different\u0000fluorescence patterns was quantified with Rand-type accuracy index, kappa index and ROC curve. It is\u0000concluded that basic models trained on a limited dataset allowed positive/negative discrimination with\u0000an efficiency comparable to that obtained by conventional analysis performed by humans (0.84 kappa\u0000score). More extensive datasets may be required for efficient discrimination between different\u0000fluorescence patterns generated by different auto-antibody species.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139585892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-25DOI: 10.1101/2024.01.25.24301776
Anna Paffrath, Laura Kim, Claudia Kedor, Elisa Stein, Rebekka Rust, Helma Freitag, Uta Hoppmann, Leif G Hanitsch, Judith Bellmann-Strobl, Kirsten Wittke, Carmen Scheibenbogen, Franziska Sotzny
Post-COVID Syndrome (PCS) refers to a diverse array of symptoms that persist beyond 3 months of the acute phase of a SARS-CoV-2 infection. The most frequent symptom is fatigue, which can manifest both mentally and physically. In this study, handgrip strength (HGS) parameters were determined as an objective measure of muscle fatigue and fatigability. HGS parameters were correlated with other fre-quent symptoms among 144 female PCS patients suffering from fatigue, exertional intolerance, and cognitive impairment. Seventy-eight patients met the Canadian Consensus Criteria (CCC) for post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The severity of disa-bility and key symptoms were evaluated utilizing self-reported questionnaires. Notably, patients di-agnosed with ME/CFS exhibited a higher overall severity of symptoms, including lower physical func-tion (p < 0.001), a greater degree of disability (p < 0.001), more severe fatigue (p < 0.001), post-exertional malaise (p < 0.001), and autonomic dysfunction (p = 0.004). While HGS was similarly impaired in both PCS and ME/CFS patients, the associations between HGS and the severity of symptoms and disability revealed striking differences. We observed significant correlations of HGS parameters with physical function across all patients, but with the key symptoms PEM, fatigue, cog-nitive impairment, and autonomic dysfunction in ME/CFS patients only. This points to a common mechanism for these symptoms in the ME/CFS subtype, distinct from that in other types of PCS. Further HGS provides an objective marker of disease severity in ME/CFS.
{"title":"Repeated Hand Grip Strength is an Objective Marker for Disability and Severity of Key Symptoms in Post-COVID ME/CFS","authors":"Anna Paffrath, Laura Kim, Claudia Kedor, Elisa Stein, Rebekka Rust, Helma Freitag, Uta Hoppmann, Leif G Hanitsch, Judith Bellmann-Strobl, Kirsten Wittke, Carmen Scheibenbogen, Franziska Sotzny","doi":"10.1101/2024.01.25.24301776","DOIUrl":"https://doi.org/10.1101/2024.01.25.24301776","url":null,"abstract":"Post-COVID Syndrome (PCS) refers to a diverse array of symptoms that persist beyond 3 months of the acute phase of a SARS-CoV-2 infection. The most frequent symptom is fatigue, which can manifest both mentally and physically. In this study, handgrip strength (HGS) parameters were determined as an objective measure of muscle fatigue and fatigability. HGS parameters were correlated with other fre-quent symptoms among 144 female PCS patients suffering from fatigue, exertional intolerance, and cognitive impairment. Seventy-eight patients met the Canadian Consensus Criteria (CCC) for post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The severity of disa-bility and key symptoms were evaluated utilizing self-reported questionnaires. Notably, patients di-agnosed with ME/CFS exhibited a higher overall severity of symptoms, including lower physical func-tion (p < 0.001), a greater degree of disability (p < 0.001), more severe fatigue (p < 0.001), post-exertional malaise (p < 0.001), and autonomic dysfunction (p = 0.004). While HGS was similarly impaired in both PCS and ME/CFS patients, the associations between HGS and the severity of symptoms and disability revealed striking differences. We observed significant correlations of HGS parameters with physical function across all patients, but with the key symptoms PEM, fatigue, cog-nitive impairment, and autonomic dysfunction in ME/CFS patients only. This points to a common mechanism for these symptoms in the ME/CFS subtype, distinct from that in other types of PCS. Further HGS provides an objective marker of disease severity in ME/CFS.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139585901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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