Dory Kovacs, Ivan Mambule, Jonathan M Read, Anmol Kiran, Moses Chilombe, Thandiwe Bvumbwe, Stephen Aston, Mavis Menyere, Mazuba Masina, Moses Kamzati, Thokozani Namale Ganiza, Danielle Iuliano, Meredith McMorrow, Naor Bar-Zeev, Dean Everett, Neil French, Antonia Ho
Background: The aim of this study was to characterize the epidemiology of human seasonal coronaviruses (HCoVs) in southern Malawi.
Methods: We tested for HCoVs 229E, OC43, NL63, and HKU1 using real-time polymerase chain reaction (PCR) on upper respiratory specimens from asymptomatic controls and individuals of all ages recruited through severe acute respiratory illness (SARI) surveillance at Queen Elizabeth Central Hospital, Blantyre, and a prospective influenza-like illness (ILI) observational study between 2011 and 2017. We modeled the probability of having a positive PCR for each HCoV using negative binomial models, and calculated pathogen-attributable fractions (PAFs).
Results: Overall, 8.8% (539/6107) of specimens were positive for ≥1 HCoV. OC43 was the most frequently detected HCoV (3.1% [191/6107]). NL63 was more frequently detected in ILI patients (adjusted incidence rate ratio [aIRR], 9.60 [95% confidence interval {CI}, 3.25-28.30]), while 229E (aIRR, 8.99 [95% CI, 1.81-44.70]) was more frequent in SARI patients than asymptomatic controls. In adults, 229E and OC43 were associated with SARI (PAF, 86.5% and 89.4%, respectively), while NL63 was associated with ILI (PAF, 85.1%). The prevalence of HCoVs was similar between children with SARI and controls. All HCoVs had bimodal peaks but distinct seasonality.
Conclusions: OC43 was the most prevalent HCoV in acute respiratory illness of all ages. Individual HCoVs had distinct seasonality that differed from temperate settings.
{"title":"Epidemiology of Human Seasonal Coronaviruses Among People With Mild and Severe Acute Respiratory Illness in Blantyre, Malawi, 2011-2017.","authors":"Dory Kovacs, Ivan Mambule, Jonathan M Read, Anmol Kiran, Moses Chilombe, Thandiwe Bvumbwe, Stephen Aston, Mavis Menyere, Mazuba Masina, Moses Kamzati, Thokozani Namale Ganiza, Danielle Iuliano, Meredith McMorrow, Naor Bar-Zeev, Dean Everett, Neil French, Antonia Ho","doi":"10.1093/infdis/jiad587","DOIUrl":"10.1093/infdis/jiad587","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to characterize the epidemiology of human seasonal coronaviruses (HCoVs) in southern Malawi.</p><p><strong>Methods: </strong>We tested for HCoVs 229E, OC43, NL63, and HKU1 using real-time polymerase chain reaction (PCR) on upper respiratory specimens from asymptomatic controls and individuals of all ages recruited through severe acute respiratory illness (SARI) surveillance at Queen Elizabeth Central Hospital, Blantyre, and a prospective influenza-like illness (ILI) observational study between 2011 and 2017. We modeled the probability of having a positive PCR for each HCoV using negative binomial models, and calculated pathogen-attributable fractions (PAFs).</p><p><strong>Results: </strong>Overall, 8.8% (539/6107) of specimens were positive for ≥1 HCoV. OC43 was the most frequently detected HCoV (3.1% [191/6107]). NL63 was more frequently detected in ILI patients (adjusted incidence rate ratio [aIRR], 9.60 [95% confidence interval {CI}, 3.25-28.30]), while 229E (aIRR, 8.99 [95% CI, 1.81-44.70]) was more frequent in SARI patients than asymptomatic controls. In adults, 229E and OC43 were associated with SARI (PAF, 86.5% and 89.4%, respectively), while NL63 was associated with ILI (PAF, 85.1%). The prevalence of HCoVs was similar between children with SARI and controls. All HCoVs had bimodal peaks but distinct seasonality.</p><p><strong>Conclusions: </strong>OC43 was the most prevalent HCoV in acute respiratory illness of all ages. Individual HCoVs had distinct seasonality that differed from temperate settings.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nelli Westercamp, Lawrence Osei-Tutu, Lode Schuerman, Simon K Kariuki, Anne Bollaerts, Cynthia K Lee, Aaron M Samuels, Christian Ockenhouse, Dennis K Bii, Samuel Adjei, Martina Oneko, Marc Lievens, Maame Anima Attobrah Sarfo, Cecilia Atieno, Ashura Bakari, Tony Sang, Maame Fremah Kotoh-Mortty, Kephas Otieno, François Roman, Patrick Boakye Yiadom Buabeng, Yaw Ntiamoah, Daniel Ansong, Tsiri Agbenyega, Opokua Ofori-Anyinam
Background: The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya.
Methods: In total, 1500 children aged 5-17 months were randomized (1:1:1:1:1) to receive RTS,S or rabies control vaccine. RTS,S groups received 2 full RTS,S doses at months 0 and 1 and either full (groups R012-20, R012-14-26) or fractional doses (one-fifth; groups Fx012-14-26, Fx017-20-32).
Results: At month 32 post-dose 1, vaccine efficacy against clinical malaria (all episodes) ranged from 38% (R012-20; 95% confidence interval [CI]: 24%-49%) to 53% (R012-14-26; 95% CI: 42%-62%). Vaccine impact (cumulative number of cases averted/1000 children vaccinated) was 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), and 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional vs full dose; post hoc analysis), we estimated cases averted/1000 RTS,S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), and 880 (Fx017-20-32).
Conclusions: Vaccine efficacy was similar across RTS,S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If maintained through trial end, these observations underscore the means to reduce cost per regimen thus maximizing impact and optimizing supply.
{"title":"Could Less Be More? Accounting for Fractional-Dose Regimens and Different Number of Vaccine Doses When Measuring the Impact of the RTS,S/AS01E Malaria Vaccine.","authors":"Nelli Westercamp, Lawrence Osei-Tutu, Lode Schuerman, Simon K Kariuki, Anne Bollaerts, Cynthia K Lee, Aaron M Samuels, Christian Ockenhouse, Dennis K Bii, Samuel Adjei, Martina Oneko, Marc Lievens, Maame Anima Attobrah Sarfo, Cecilia Atieno, Ashura Bakari, Tony Sang, Maame Fremah Kotoh-Mortty, Kephas Otieno, François Roman, Patrick Boakye Yiadom Buabeng, Yaw Ntiamoah, Daniel Ansong, Tsiri Agbenyega, Opokua Ofori-Anyinam","doi":"10.1093/infdis/jiae075","DOIUrl":"10.1093/infdis/jiae075","url":null,"abstract":"<p><strong>Background: </strong>The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya.</p><p><strong>Methods: </strong>In total, 1500 children aged 5-17 months were randomized (1:1:1:1:1) to receive RTS,S or rabies control vaccine. RTS,S groups received 2 full RTS,S doses at months 0 and 1 and either full (groups R012-20, R012-14-26) or fractional doses (one-fifth; groups Fx012-14-26, Fx017-20-32).</p><p><strong>Results: </strong>At month 32 post-dose 1, vaccine efficacy against clinical malaria (all episodes) ranged from 38% (R012-20; 95% confidence interval [CI]: 24%-49%) to 53% (R012-14-26; 95% CI: 42%-62%). Vaccine impact (cumulative number of cases averted/1000 children vaccinated) was 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), and 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional vs full dose; post hoc analysis), we estimated cases averted/1000 RTS,S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), and 880 (Fx017-20-32).</p><p><strong>Conclusions: </strong>Vaccine efficacy was similar across RTS,S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If maintained through trial end, these observations underscore the means to reduce cost per regimen thus maximizing impact and optimizing supply.</p><p><strong>Clinical trials registration: </strong>NCT03276962 (ClinicalTrials.gov).</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11326831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pia L Esser, Gibran H Rubio Quintanares, Bettina Langhans, Eva Heger, Michael Böhm, Björn-Erik O L E Jensen, Stefan Esser, Nadine Lübke, Gerd Fätkenheuer, Thomas Lengauer, Florian Klein, Mark Oette, Juergen K Rockstroh, Christoph Boesecke, Veronica Di Cristanziano, Rolf Kaiser, Martin Pirkl
Background: Torque teno virus (TTV) is part of the human virome. TTV load was related to the immune status in patients after organ transplantation. We hypothesize that TTV load could be an additional marker for immune function in people living with HIV (PLWH).
Methods: In this analysis, serum samples of PLWH from the RESINA multicenter cohort were reanalyzed for TTV. Investigated clinical and epidemiological parameters included human pegivirus load, patient age and sex, HIV load, CD4+ T-cell count (Centers for Disease Control and Prevention [CDC] stage 1, 2, or 3), and CDC clinical stage (1993 CDC classification system; stage A, B, or C) before initiation of antiretroviral therapy. Regression analysis was used to detect possible associations among parameters.
Results: Our analysis confirmed TTV as a strong predictor of CD4+ T-cell count and CDC class 3. This relationship was used to propose a first classification of TTV load with regard to clinical stage. We found no association with clinical CDC stages A-C. The human pegivirus load was inversely correlated with HIV load but not TTV load.
Conclusions: TTV load was associated with immunodeficiency in PLWH. Neither TTV nor HIV load were predictive for the clinical categories of HIV infection.
背景:托克-特诺病毒(TTV)是一种无包膜、环状单链 DNA 病毒,也是人类病毒群的一部分。在器官移植后接受免疫抑制药物治疗的患者中,TTV 的复制与免疫状态有关。我们假设 TTV 的负荷量可以作为 HIV 感染者(PLWH)免疫功能的额外标记:在这项分析中,我们重新分析了 RESINA 多中心队列中艾滋病病毒感染者的血清样本中的 TTV。调查的临床和流行病学参数包括Pegivirus (HPgV)载量、年龄、性别、HIV载量、CD4+细胞计数(CDC 1、2、3)和开始抗逆转录病毒治疗前的CDC临床分期(1993年CDC分类系统,A、B、C)。我们使用回归分析来检测各参数之间可能存在的关联:结果:我们的分析证实,TTV 对 CD4+ 细胞计数和 CDC 3 级有很强的预测作用。根据这一关系,我们首次提出了TTV载量与临床分期的关系。HPgV载量与HIV载量成反比,但与TTV载量无关:结论:TTV载量与艾滋病毒感染者的免疫缺陷有关。结论:TTV载量与艾滋病毒感染者的免疫缺陷有关,TTV载量和艾滋病毒载量都不能预测艾滋病毒感染的临床类别。
{"title":"Torque Teno Virus Load Is Associated With Centers for Disease Control and Prevention Stage and CD4+ Cell Count in People Living With Human Immunodeficiency Virus but Seems Unrelated to AIDS-Defining Events and Human Pegivirus Load.","authors":"Pia L Esser, Gibran H Rubio Quintanares, Bettina Langhans, Eva Heger, Michael Böhm, Björn-Erik O L E Jensen, Stefan Esser, Nadine Lübke, Gerd Fätkenheuer, Thomas Lengauer, Florian Klein, Mark Oette, Juergen K Rockstroh, Christoph Boesecke, Veronica Di Cristanziano, Rolf Kaiser, Martin Pirkl","doi":"10.1093/infdis/jiae014","DOIUrl":"10.1093/infdis/jiae014","url":null,"abstract":"<p><strong>Background: </strong>Torque teno virus (TTV) is part of the human virome. TTV load was related to the immune status in patients after organ transplantation. We hypothesize that TTV load could be an additional marker for immune function in people living with HIV (PLWH).</p><p><strong>Methods: </strong>In this analysis, serum samples of PLWH from the RESINA multicenter cohort were reanalyzed for TTV. Investigated clinical and epidemiological parameters included human pegivirus load, patient age and sex, HIV load, CD4+ T-cell count (Centers for Disease Control and Prevention [CDC] stage 1, 2, or 3), and CDC clinical stage (1993 CDC classification system; stage A, B, or C) before initiation of antiretroviral therapy. Regression analysis was used to detect possible associations among parameters.</p><p><strong>Results: </strong>Our analysis confirmed TTV as a strong predictor of CD4+ T-cell count and CDC class 3. This relationship was used to propose a first classification of TTV load with regard to clinical stage. We found no association with clinical CDC stages A-C. The human pegivirus load was inversely correlated with HIV load but not TTV load.</p><p><strong>Conclusions: </strong>TTV load was associated with immunodeficiency in PLWH. Neither TTV nor HIV load were predictive for the clinical categories of HIV infection.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11326818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manish C Choudhary, Rinki Deo, Teresa H Evering, Kara W Chew, Mark J Giganti, Carlee Moser, Justin Ritz, James Regan, James P Flynn, Charles R Crain, David Alain Wohl, Judith S Currier, Joseph J Eron, David Margolis, Qing Zhu, Lijie Zhon, Li Ya, Alexander L Greninger, Michael D Hughes, Davey Smith, Eric S Daar, Jonathan Z Li
Background: Monoclonal antibodies (mAbs) represent a crucial antiviral strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether combination mAbs offer a benefit over single-active mAb treatment. Amubarvimab and romlusevimab significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. Certain SARS-CoV-2 variants are intrinsically resistant against romlusevimab, leading to only single-active mAb therapy with amubarvimab in these variants. We evaluated virologic outcomes in individuals treated with single- versus dual-active mAbs.
Methods: Participants were nonhospitalized adults at higher risk of clinical progression randomized to amubarvimab plus romlusevimab or placebo. Quantitative SARS-CoV-2 RNA levels and targeted S-gene next-generation sequencing was performed on anterior nasal samples. We compared viral load kinetics and resistance emergence between individuals treated with effective single- versus dual-active mAbs depending on the infecting variant.
Results: Study participants receiving single- or dual-active mAbs had similar demographics, baseline nasal viral load, symptom score, and symptom duration. Compared with single-active mAb treatment, treatment with dual-active mAbs led to faster viral load decline at study days 3 (P < .001) and 7 (P < .01). Treatment-emergent resistance mutations were more likely to be detected after amubarvimab plus romlusevimab treatment than with placebo (2.6% vs 0%; P < .001) and were more frequently detected in the setting of single-active compared with dual-active mAb treatment (7.3% vs 1.1%; P < .01). Single-active and dual-active mAb treatment resulted in similar decrease in rates of hospitalizations or death.
Conclusions: Compared with single-active mAb therapy, dual-active mAbs led to similar clinical outcomes but significantly faster viral load decline and a lower risk of emergent resistance.
背景:单克隆抗体(mAb)是治疗SARS-CoV-2感染的重要抗病毒策略,但目前尚不清楚联合mAb治疗是否比单一活性mAb治疗更有效。在 ACTIV-2/A5401 试验中,Amubarvimab 和 romlusevimab 能显著降低住院或死亡风险。某些 SARS-CoV-2 变体对罗姆卢舍单抗具有内在耐药性,因此只能对这些变体使用阿穆巴单抗进行单活性 mAb 治疗。我们评估了接受单活性与双活性 mAb 治疗者的病毒学结果:参试者为非住院的临床进展风险较高的成人,随机接受阿穆巴单抗加罗姆单抗或安慰剂治疗。对前鼻腔样本进行SARS-CoV-2 RNA水平定量分析和S基因下一代靶向测序。根据感染变异株,我们比较了接受有效单药和双药 mAbs 治疗的患者的病毒载量动力学和耐药性出现情况:结果:接受单效和双效 mAb 治疗的研究人员具有相似的人口统计学特征、基线鼻病毒载量、症状评分和症状持续时间。与单一活性 mAb 相比,接受双活性 mAb 治疗的患者在研究第 3 天的病毒载量下降速度更快(p 结论:与单一活性 mAb 相比,接受双活性 mAb 治疗的患者在研究第 3 天的病毒载量下降速度更快(p 结论):与单活性 mAb 治疗相比,双活性 mAb 可带来相似的临床结果,但病毒载量下降速度更快,出现耐药性的风险更低。
{"title":"Characterization of Treatment Resistance and Viral Kinetics in the Setting of Single-Active Versus Dual-Active Monoclonal Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2.","authors":"Manish C Choudhary, Rinki Deo, Teresa H Evering, Kara W Chew, Mark J Giganti, Carlee Moser, Justin Ritz, James Regan, James P Flynn, Charles R Crain, David Alain Wohl, Judith S Currier, Joseph J Eron, David Margolis, Qing Zhu, Lijie Zhon, Li Ya, Alexander L Greninger, Michael D Hughes, Davey Smith, Eric S Daar, Jonathan Z Li","doi":"10.1093/infdis/jiae192","DOIUrl":"10.1093/infdis/jiae192","url":null,"abstract":"<p><strong>Background: </strong>Monoclonal antibodies (mAbs) represent a crucial antiviral strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether combination mAbs offer a benefit over single-active mAb treatment. Amubarvimab and romlusevimab significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. Certain SARS-CoV-2 variants are intrinsically resistant against romlusevimab, leading to only single-active mAb therapy with amubarvimab in these variants. We evaluated virologic outcomes in individuals treated with single- versus dual-active mAbs.</p><p><strong>Methods: </strong>Participants were nonhospitalized adults at higher risk of clinical progression randomized to amubarvimab plus romlusevimab or placebo. Quantitative SARS-CoV-2 RNA levels and targeted S-gene next-generation sequencing was performed on anterior nasal samples. We compared viral load kinetics and resistance emergence between individuals treated with effective single- versus dual-active mAbs depending on the infecting variant.</p><p><strong>Results: </strong>Study participants receiving single- or dual-active mAbs had similar demographics, baseline nasal viral load, symptom score, and symptom duration. Compared with single-active mAb treatment, treatment with dual-active mAbs led to faster viral load decline at study days 3 (P < .001) and 7 (P < .01). Treatment-emergent resistance mutations were more likely to be detected after amubarvimab plus romlusevimab treatment than with placebo (2.6% vs 0%; P < .001) and were more frequently detected in the setting of single-active compared with dual-active mAb treatment (7.3% vs 1.1%; P < .01). Single-active and dual-active mAb treatment resulted in similar decrease in rates of hospitalizations or death.</p><p><strong>Conclusions: </strong>Compared with single-active mAb therapy, dual-active mAbs led to similar clinical outcomes but significantly faster viral load decline and a lower risk of emergent resistance.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11326811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anthony M Marchese, Matthew Rousculp, John Macbeth, Hadi Beyhaghi, Bruce T Seet, Seth Toback
Coronavirus disease 2019 (COVID-19) continues to be a global health concern, and booster doses are necessary for maintaining vaccine-mediated protection, limiting the spread of severe acute respiratory syndrome coronavirus 2. Despite multiple COVID-19 vaccine options, global booster uptake remains low. Reactogenicity, the occurrence of adverse local/systemic side effects, plays a crucial role in vaccine uptake and acceptance, particularly for booster doses. We conducted a targeted review of the reactogenicity of authorized/approved messenger RNA (mRNA) and protein-based vaccines demonstrated by clinical trials and real-world evidence. It was found that mRNA-based boosters show a higher incidence and an increased severity of reactogenicity compared with the Novavax protein-based COVID-19 vaccine (NVX-CoV2373). In a recent study from the National Institute of Allergy and Infectious Diseases, the incidence of pain/tenderness, swelling, erythema, fatigue/malaise, headache, muscle pain, or fever was higher in individuals boosted with BNT162b2 (0.4% to 41.6% absolute increase) or mRNA-1273 (5.5% to 55.0% absolute increase) compared with NVX-CoV2373. Evidence suggests that NVX-CoV2373, when utilized as a heterologous booster, demonstrates less reactogenicity compared with mRNA vaccines, which, if communicated to hesitant individuals, may strengthen booster uptake rates worldwide. Clinical Trials Registration NCT04889209.
{"title":"The Novavax Heterologous Coronavirus Disease 2019 Booster Demonstrates Lower Reactogenicity Than Messenger RNA: A Targeted Review.","authors":"Anthony M Marchese, Matthew Rousculp, John Macbeth, Hadi Beyhaghi, Bruce T Seet, Seth Toback","doi":"10.1093/infdis/jiad519","DOIUrl":"10.1093/infdis/jiad519","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) continues to be a global health concern, and booster doses are necessary for maintaining vaccine-mediated protection, limiting the spread of severe acute respiratory syndrome coronavirus 2. Despite multiple COVID-19 vaccine options, global booster uptake remains low. Reactogenicity, the occurrence of adverse local/systemic side effects, plays a crucial role in vaccine uptake and acceptance, particularly for booster doses. We conducted a targeted review of the reactogenicity of authorized/approved messenger RNA (mRNA) and protein-based vaccines demonstrated by clinical trials and real-world evidence. It was found that mRNA-based boosters show a higher incidence and an increased severity of reactogenicity compared with the Novavax protein-based COVID-19 vaccine (NVX-CoV2373). In a recent study from the National Institute of Allergy and Infectious Diseases, the incidence of pain/tenderness, swelling, erythema, fatigue/malaise, headache, muscle pain, or fever was higher in individuals boosted with BNT162b2 (0.4% to 41.6% absolute increase) or mRNA-1273 (5.5% to 55.0% absolute increase) compared with NVX-CoV2373. Evidence suggests that NVX-CoV2373, when utilized as a heterologous booster, demonstrates less reactogenicity compared with mRNA vaccines, which, if communicated to hesitant individuals, may strengthen booster uptake rates worldwide. Clinical Trials Registration NCT04889209.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11326839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138296385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nerea Hermida, Murdo Ferguson, Isabel Leroux-Roels, Sandra Pagnussat, Deborah Yaplee, Nancy Hua, Peter van den Steen, Bruno Anspach, Ilse Dieussaert, Joon Hyung Kim
Background: Respiratory syncytial virus (RSV) fusion protein stabilized in the prefusion conformation (RSVPreF3) was under investigation as a maternal vaccine.
Methods: This phase 2, randomized, placebo-controlled, single-dose, multicenter study enrolled healthy, nonpregnant women, randomized 1:1:1:1:1 to 5 parallel groups studying RSVPreF3 (60 or 120 µg) coadministered with diphtheria, tetanus, and acellular pertussis vaccine (dTpa) or placebo, and dTpa coadministered with placebo. Safety and humoral immune responses were assessed. An extension phase also assessed a RSVPreF3 120 μg vaccination 12-18 months after first vaccination.
Results: The safety profile of RSVPreF3 was unaffected by dose or dTpa coadministration. Solicited and unsolicited adverse events (AEs) were evenly distributed across study groups. Injection-site pain was higher following the second vaccination versus the first vaccination. Medically attended AEs were rare (<5% overall). Both RSVPreF3 dose levels (alone and with dTpa) were immunogenic, increasing levels of RSV-A neutralizing antibody ≥8-fold and anti-RSVPreF3 IgG antibody ≥11-fold at 1 month postvaccination, which persisted at 12-18 months postvaccination; modest 2-fold increases were observed with a second RSVPreF3 vaccination.
Conclusions: This study indicates RSVPreF3 coadministration with dTpa induces robust immune responses and is well tolerated, regardless of the RSVPreF3 dose level used.
{"title":"Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion Maternal Vaccine Coadministered With Diphtheria-Tetanus-Pertussis Vaccine: A Phase 2 Study.","authors":"Nerea Hermida, Murdo Ferguson, Isabel Leroux-Roels, Sandra Pagnussat, Deborah Yaplee, Nancy Hua, Peter van den Steen, Bruno Anspach, Ilse Dieussaert, Joon Hyung Kim","doi":"10.1093/infdis/jiad560","DOIUrl":"10.1093/infdis/jiad560","url":null,"abstract":"<p><strong>Background: </strong>Respiratory syncytial virus (RSV) fusion protein stabilized in the prefusion conformation (RSVPreF3) was under investigation as a maternal vaccine.</p><p><strong>Methods: </strong>This phase 2, randomized, placebo-controlled, single-dose, multicenter study enrolled healthy, nonpregnant women, randomized 1:1:1:1:1 to 5 parallel groups studying RSVPreF3 (60 or 120 µg) coadministered with diphtheria, tetanus, and acellular pertussis vaccine (dTpa) or placebo, and dTpa coadministered with placebo. Safety and humoral immune responses were assessed. An extension phase also assessed a RSVPreF3 120 μg vaccination 12-18 months after first vaccination.</p><p><strong>Results: </strong>The safety profile of RSVPreF3 was unaffected by dose or dTpa coadministration. Solicited and unsolicited adverse events (AEs) were evenly distributed across study groups. Injection-site pain was higher following the second vaccination versus the first vaccination. Medically attended AEs were rare (<5% overall). Both RSVPreF3 dose levels (alone and with dTpa) were immunogenic, increasing levels of RSV-A neutralizing antibody ≥8-fold and anti-RSVPreF3 IgG antibody ≥11-fold at 1 month postvaccination, which persisted at 12-18 months postvaccination; modest 2-fold increases were observed with a second RSVPreF3 vaccination.</p><p><strong>Conclusions: </strong>This study indicates RSVPreF3 coadministration with dTpa induces robust immune responses and is well tolerated, regardless of the RSVPreF3 dose level used.</p><p><strong>Clinical trials registration: </strong>NCT04138056.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11326842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138832721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katerina Roznik, Temesgen E Andargie, T Scott Johnston, Oren Gordon, Yi Wang, Nadine Peart Akindele, Deborah Persaud, Annukka A R Antar, Yukari C Manabe, Weiqiang Zhou, Hongkai Ji, Sean Agbor-Enoh, Andrew H Karaba, Elizabeth A Thompson, Andrea L Cox
Background: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition caused by recent infection with severe acute respiratory syndrome coronavirus 2, but the underlying immunological mechanisms driving this distinct syndrome are unknown.
Methods: We utilized high-dimensional flow cytometry, cell-free (cf) DNA, and cytokine and chemokine profiling to identify mechanisms of critical illness distinguishing MIS-C from severe acute coronavirus disease 2019 (SAC).
Results: Compared to SAC, MIS-C patients demonstrated profound innate immune cell death and features of emergency myelopoiesis (EM), an understudied phenomenon observed in severe inflammation. EM signatures were characterized by fewer mature myeloid cells in the periphery and decreased expression of HLA-DR and CD86 on antigen-presenting cells. Interleukin 27 (IL-27), a cytokine known to drive hematopoietic stem cells toward EM, was increased in MIS-C, and correlated with immature cell signatures in MIS-C. Upon recovery, EM signatures decreased and IL-27 plasma levels returned to normal levels. Despite profound lymphopenia, we report a lack of cfDNA released by adaptive immune cells and increased CCR7 expression on T cells indicative of egress out of peripheral blood.
Conclusions: Immune cell signatures of EM combined with elevated innate immune cell-derived cfDNA levels distinguish MIS-C from SAC in children and provide mechanistic insight into dysregulated immunity contributing toward MIS-C, offering potential diagnostic and therapeutic targets.
{"title":"Emergency Myelopoiesis Distinguishes Multisystem Inflammatory Syndrome in Children From Pediatric Severe Coronavirus Disease 2019.","authors":"Katerina Roznik, Temesgen E Andargie, T Scott Johnston, Oren Gordon, Yi Wang, Nadine Peart Akindele, Deborah Persaud, Annukka A R Antar, Yukari C Manabe, Weiqiang Zhou, Hongkai Ji, Sean Agbor-Enoh, Andrew H Karaba, Elizabeth A Thompson, Andrea L Cox","doi":"10.1093/infdis/jiae032","DOIUrl":"10.1093/infdis/jiae032","url":null,"abstract":"<p><strong>Background: </strong>Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition caused by recent infection with severe acute respiratory syndrome coronavirus 2, but the underlying immunological mechanisms driving this distinct syndrome are unknown.</p><p><strong>Methods: </strong>We utilized high-dimensional flow cytometry, cell-free (cf) DNA, and cytokine and chemokine profiling to identify mechanisms of critical illness distinguishing MIS-C from severe acute coronavirus disease 2019 (SAC).</p><p><strong>Results: </strong>Compared to SAC, MIS-C patients demonstrated profound innate immune cell death and features of emergency myelopoiesis (EM), an understudied phenomenon observed in severe inflammation. EM signatures were characterized by fewer mature myeloid cells in the periphery and decreased expression of HLA-DR and CD86 on antigen-presenting cells. Interleukin 27 (IL-27), a cytokine known to drive hematopoietic stem cells toward EM, was increased in MIS-C, and correlated with immature cell signatures in MIS-C. Upon recovery, EM signatures decreased and IL-27 plasma levels returned to normal levels. Despite profound lymphopenia, we report a lack of cfDNA released by adaptive immune cells and increased CCR7 expression on T cells indicative of egress out of peripheral blood.</p><p><strong>Conclusions: </strong>Immune cell signatures of EM combined with elevated innate immune cell-derived cfDNA levels distinguish MIS-C from SAC in children and provide mechanistic insight into dysregulated immunity contributing toward MIS-C, offering potential diagnostic and therapeutic targets.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11326850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139652059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karen Sauve, Aubrey Watson, Jun T Oh, Steven Swift, Xavier Vila-Farres, Wessam Abdelhady, Yan Q Xiong, Dario LeHoux, Gary Woodnutt, Arnold S Bayer, Raymond Schuch
Background: Lysins (cell wall hydrolases) targeting gram-negative organisms require engineering to permeabilize the outer membrane and access subjacent peptidoglycan to facilitate killing. In the current study, the potential clinical utility for the engineered lysin CF-370 was examined in vitro and in vivo against gram-negative pathogens important in human infections.
Methods: Minimum inhibitory concentration (MICs) and bactericidal activity were determined using standard methods. An in vivo proof-of-concept efficacy study was conducted using a rabbit acute pneumonia model caused by Pseudomonas aeruginosa.
Results: CF-370 exhibited potent antimicrobial activity, with MIC50/90 values (in µg/mL) for: P aeruginosa, 1/2; Acinetobacter baumannii, 1/1; Escherichia coli, 0.25/1; Klebsiella pneumoniae, 2/4; Enterobacter cloacae 1/4; and Stenotrophomonas maltophilia 2/8. CF-370 furthermore demonstrated bactericidal activity, activity in serum, a low propensity for resistance, anti-biofilm activity, and synergy with antibiotics. In the pneumonia model, CF-370 alone decreased bacterial densities in lungs, kidneys, and spleen versus vehicle control, and demonstrated significantly increased efficacy when combined with meropenem (vs either agent alone).
Conclusions: CF-370 is the first engineered lysin described with potent broad-spectrum in vitro activity against multiple clinically relevant gram-negative pathogens, as well as potent in vivo efficacy in an animal model of severe invasive multisystem infection.
背景:针对革兰氏阴性菌的溶菌素(细胞壁水解酶)需要经过工程改造才能使外膜渗透,并进入邻近的肽聚糖以促进杀灭。本研究在体外和体内检测了工程溶菌素 CF-370 对人类感染中重要的革兰氏阴性病原体的潜在临床用途:方法:采用标准方法测定 MIC 和杀菌活性。方法:采用标准方法测定 MIC 和杀菌活性,并利用铜绿假单胞菌引起的兔急性肺炎模型进行了体内疗效验证研究:结果:CF-370 具有很强的抗菌活性,对铜绿假单胞菌的 MIC50/90 值(微克/毫升)为1/2;鲍曼不动杆菌(Acinetobacter baumannii),1/1;大肠埃希菌(Escherichia coli),0.25/1;肺炎克雷伯菌(Klebsiella pneumoniae),2/4;泄殖腔肠杆菌(Enterobacter cloacae),1/4;嗜麦芽血单胞菌(Stenotrophomonas maltophilia),2/8。CF-370 还表现出:i)杀菌活性;ii)血清活性;iii)低耐药性倾向;iv)抗生物膜活性;v)与抗生素的协同作用。在肺炎模型中,与药物对照组相比,CF-370 单独使用可降低肺、肾和脾中的细菌密度,与美罗培南(与单独使用其中一种药物相比)联合使用时,疗效显著提高:结论:CF-370 是第一种针对多种临床相关革兰氏阴性病原体具有强效广谱体外活性的工程溶菌素,在严重侵袭性多系统感染动物模型中也具有强效体内疗效。
{"title":"The Engineered Lysin CF-370 Is Active Against Antibiotic-Resistant Gram-Negative Pathogens In Vitro and Synergizes With Meropenem in Experimental Pseudomonas aeruginosa Pneumonia.","authors":"Karen Sauve, Aubrey Watson, Jun T Oh, Steven Swift, Xavier Vila-Farres, Wessam Abdelhady, Yan Q Xiong, Dario LeHoux, Gary Woodnutt, Arnold S Bayer, Raymond Schuch","doi":"10.1093/infdis/jiae027","DOIUrl":"10.1093/infdis/jiae027","url":null,"abstract":"<p><strong>Background: </strong>Lysins (cell wall hydrolases) targeting gram-negative organisms require engineering to permeabilize the outer membrane and access subjacent peptidoglycan to facilitate killing. In the current study, the potential clinical utility for the engineered lysin CF-370 was examined in vitro and in vivo against gram-negative pathogens important in human infections.</p><p><strong>Methods: </strong>Minimum inhibitory concentration (MICs) and bactericidal activity were determined using standard methods. An in vivo proof-of-concept efficacy study was conducted using a rabbit acute pneumonia model caused by Pseudomonas aeruginosa.</p><p><strong>Results: </strong>CF-370 exhibited potent antimicrobial activity, with MIC50/90 values (in µg/mL) for: P aeruginosa, 1/2; Acinetobacter baumannii, 1/1; Escherichia coli, 0.25/1; Klebsiella pneumoniae, 2/4; Enterobacter cloacae 1/4; and Stenotrophomonas maltophilia 2/8. CF-370 furthermore demonstrated bactericidal activity, activity in serum, a low propensity for resistance, anti-biofilm activity, and synergy with antibiotics. In the pneumonia model, CF-370 alone decreased bacterial densities in lungs, kidneys, and spleen versus vehicle control, and demonstrated significantly increased efficacy when combined with meropenem (vs either agent alone).</p><p><strong>Conclusions: </strong>CF-370 is the first engineered lysin described with potent broad-spectrum in vitro activity against multiple clinically relevant gram-negative pathogens, as well as potent in vivo efficacy in an animal model of severe invasive multisystem infection.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11326841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The family Borreliaceae contains arthropod-borne spirochetes that cause two widespread human diseases, Lyme disease and relapsing fever. Lyme disease is a subacute, progressive illness with variable stage and tissue manifestations. Relapsing fever is an acute febrile illness with prominent bacteremia that may recur and disseminate, particularly to the nervous system. Clinical heterogeneity is a hallmark of both diseases. While human clinical manifestations are influenced by a wide variety of factors, including immune status and host genetic susceptibility, there is evidence that Borreliaceae microbial factors influence the clinical manifestations of human disease caused by this family of spirochetes. Despite these associations, the spirochete genes that influence the severity and manifestations of human disease are, for the most part, unknown. Recent work has identified lineage-specific expansions of lipoproteome-rich accessory genome elements in virulent clones of Borrelia burgdorferi. Using publicly available genome assemblies, it is shown that all Borreliaceae lineages for which sufficient sequence data are available harbor a similar pattern of strongly structured, lineage-specific expansions in their accessory genomes, particularly among lipoproteins, and that this pattern holds across phylogenetic scales including genera, species, and genotypes. The relationships among pangenome elements suggest that infrequent episodes of marked genomic change followed by clonal expansion in geographically and enzootically structured populations may account for the unique lineage structure of Borreliaceae. This analysis informs future genotype-phenotype studies among Borreliaceae and lays a foundation for studies of individual gene function guided by phylogenetic patterns of conservation, diversification, gain, and/or loss.
{"title":"Analysis of the Borreliaceae Pangenome Reveals a Distinct Genomic Architecture Conserved Across Phylogenetic Scales.","authors":"Jacob E Lemieux","doi":"10.1093/infdis/jiae256","DOIUrl":"https://doi.org/10.1093/infdis/jiae256","url":null,"abstract":"<p><p>The family Borreliaceae contains arthropod-borne spirochetes that cause two widespread human diseases, Lyme disease and relapsing fever. Lyme disease is a subacute, progressive illness with variable stage and tissue manifestations. Relapsing fever is an acute febrile illness with prominent bacteremia that may recur and disseminate, particularly to the nervous system. Clinical heterogeneity is a hallmark of both diseases. While human clinical manifestations are influenced by a wide variety of factors, including immune status and host genetic susceptibility, there is evidence that Borreliaceae microbial factors influence the clinical manifestations of human disease caused by this family of spirochetes. Despite these associations, the spirochete genes that influence the severity and manifestations of human disease are, for the most part, unknown. Recent work has identified lineage-specific expansions of lipoproteome-rich accessory genome elements in virulent clones of Borrelia burgdorferi. Using publicly available genome assemblies, it is shown that all Borreliaceae lineages for which sufficient sequence data are available harbor a similar pattern of strongly structured, lineage-specific expansions in their accessory genomes, particularly among lipoproteins, and that this pattern holds across phylogenetic scales including genera, species, and genotypes. The relationships among pangenome elements suggest that infrequent episodes of marked genomic change followed by clonal expansion in geographically and enzootically structured populations may account for the unique lineage structure of Borreliaceae. This analysis informs future genotype-phenotype studies among Borreliaceae and lays a foundation for studies of individual gene function guided by phylogenetic patterns of conservation, diversification, gain, and/or loss.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rebecca Danner, Lauren M Prochniak, Michaela Pereckas, Joseph R Rouse, Amanda Wahhab, Lauren G Hackner, Robert B Lochhead
Background: During infection with the Lyme arthritis (LA) pathogen Borrelia burgdorferi, T-cell responses to both host and pathogen are dysregulated, resulting in chronic infection and frequent development of autoimmunity.
Methods: To assess CD4+ T-cell epitopes presented during development of LA, we used an unbiased, immunopeptidomics approach to characterize the major histocompatibility complex (MHC) class II immunopeptidome in B burgdorferi-infected C57BL/6 (B6) mice, which develop mild, self-limiting LA, and infected B6 Il10-/- mice, which develop severe, persistent LA at 0, 4, and 16 weeks postinfection (22-23 mice per group).
Results: Peptides derived from proteins involved in adaptive T- and B-cell responses and cholesterol metabolism, including human Lyme autoantigen apolipoprotein B-100 (apoB-100), were enriched in infected Il10-/- mice; whereas peptides derived from proteins involved in neutrophil extracellular net formation were enriched in infected B6 mice. Presentation of apoB-100 peptides showed evidence of epitope expansion during infection. Of several identified B burgdorferi peptides, only 1, a methyl-accepting chemotaxis protein peptide Mcp4442-462, was immunogenic.
Conclusions: ApoB-100, a human Lyme autoantigen, undergoes marked epitope expansion during LA development. The paucity of immunogenic B burgdorferi epitopes supports previous findings suggesting CD4+ T-cell responses are suppressed in murine LA.
背景:在感染莱姆关节炎(LA)病原体鲍瑞氏菌(Borrelia burgdorferi)期间,宿主和病原体的T细胞反应失调,导致慢性感染和自身免疫的频繁发生:为了评估在LA发展过程中出现的CD4+ T细胞表位,我们使用了一种无偏见的免疫肽组学方法来描述Burgdorferi感染的C57BL/6(B6)小鼠和感染的B6 Il10-/-小鼠(每组22-23只小鼠)的主要组织相容性复合体(MHC)II类免疫肽组(前者在感染后0、4和16周出现轻度、自限性LA,后者则出现重度、持续性LA):结果:受感染的Il10-/-小鼠体内富集了来自参与适应性T细胞和B细胞反应及胆固醇代谢的蛋白质的肽,包括人类莱姆自身抗原载脂蛋白B-100(apoB-100);而受感染的B6小鼠体内富集了来自参与中性粒细胞胞外网形成的蛋白质的肽。在感染过程中,apoB-100多肽的表达显示了表位扩展的证据。在几种已确定的B burgdorferi肽中,只有1种(甲基接受趋化蛋白肽Mcp4442-462)具有免疫原性:结论:ApoB-100是人类莱姆自身抗原,在LA发育过程中会出现明显的表位扩展。免疫原 B burgdorferi 表位的缺乏支持了之前的研究结果,即 CD4+ T 细胞反应在小鼠 LA 中受到抑制。
{"title":"Identification of Major Histocompatibility Complex Class II Epitopes From Lyme Autoantigen Apolipoprotein B-100 and Borrelia burgdorferi Mcp4 in Murine Lyme Arthritis.","authors":"Rebecca Danner, Lauren M Prochniak, Michaela Pereckas, Joseph R Rouse, Amanda Wahhab, Lauren G Hackner, Robert B Lochhead","doi":"10.1093/infdis/jiae324","DOIUrl":"10.1093/infdis/jiae324","url":null,"abstract":"<p><strong>Background: </strong>During infection with the Lyme arthritis (LA) pathogen Borrelia burgdorferi, T-cell responses to both host and pathogen are dysregulated, resulting in chronic infection and frequent development of autoimmunity.</p><p><strong>Methods: </strong>To assess CD4+ T-cell epitopes presented during development of LA, we used an unbiased, immunopeptidomics approach to characterize the major histocompatibility complex (MHC) class II immunopeptidome in B burgdorferi-infected C57BL/6 (B6) mice, which develop mild, self-limiting LA, and infected B6 Il10-/- mice, which develop severe, persistent LA at 0, 4, and 16 weeks postinfection (22-23 mice per group).</p><p><strong>Results: </strong>Peptides derived from proteins involved in adaptive T- and B-cell responses and cholesterol metabolism, including human Lyme autoantigen apolipoprotein B-100 (apoB-100), were enriched in infected Il10-/- mice; whereas peptides derived from proteins involved in neutrophil extracellular net formation were enriched in infected B6 mice. Presentation of apoB-100 peptides showed evidence of epitope expansion during infection. Of several identified B burgdorferi peptides, only 1, a methyl-accepting chemotaxis protein peptide Mcp4442-462, was immunogenic.</p><p><strong>Conclusions: </strong>ApoB-100, a human Lyme autoantigen, undergoes marked epitope expansion during LA development. The paucity of immunogenic B burgdorferi epitopes supports previous findings suggesting CD4+ T-cell responses are suppressed in murine LA.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}