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1.
West J Nurs Res ; 46(3): 229-235, 2024 03.
Article in English | MEDLINE | ID: mdl-38318811

ABSTRACT

BACKGROUND: The coronavirus (COVID-19) pandemic profoundly impacted patient care across the United States. OBJECTIVE: To examine nursing staffs' perceptions of the COVID-19 vaccine using the Health Belief Model (HBM) as a theoretical framework. METHODS: A cross-sectional, anonymous, web-based survey was completed by practicing nursing staffs throughout the United States. Analyses involved descriptive and comparative statistics. RESULTS: Of the 294 nursing staff who completed surveys, 50% were between 18 and 37 years of age, and 73.1% were registered nurses, with 49.3% employed in a hospital setting. Nursing staff reported their primary reason for vaccination was concern for others (mean: 84.44; SD: 28.26), vaccine prevents spread (mean: 81.85; SD: 28.94), and own health (mean: 79.63; SD: 30.0). Influencing factors that predicted vaccination included age, Wilks' Λ = 0.76, F(32, 919.86) = 2.20, p < .001, η2partial = 0.066, and the vaccine mandate, Wilks' Λ = 0.63, F(8, 249) = 18.61, p < .001, η2partial = 0.374. CONCLUSION: Nursing staffs' perceptions using the HBM as a theoretical framework provided insight into their decisions to receive the COVID-19 vaccine. Further research is warranted to examine nurses' attitudes and factors that influence their decision-making regarding vaccination.


Subject(s)
COVID-19 , Nursing Staff , Humans , United States , Aged , COVID-19 Vaccines , COVID-19/prevention & control , Cross-Sectional Studies , Health Belief Model
2.
J Cancer Surviv ; 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38361104

ABSTRACT

PURPOSE: The aim of the literature review was to identify and synthesise research on self-care advice for oesophageal cancer survivors. METHODS: A mixed-methods systematic review and synthesis of existing literature on the topic. Five databases were searched for studies providing information on self-care advice for survivorship after oesophageal cancer surgery, in English, with no time filter. The Critical Appraisal Skills Program was used to assess the risk of bias. Data were presented by textual descriptions and grouping of data. RESULTS: Among the 13 studies included in the review, five pieces of self-care advice were identified; reconstructing eating habits, bed-head elevation, health-promoting advice, monitoring symptoms and body functions, and involving family and friends. The self-care advice was experienced to be hard work, but worth the effort. They also provided reassurance and an increased understanding of bodily changes and social consequences of the disease and treatment. CONCLUSIONS: There are is little evidence-based self-care advice for oesophageal cancer survivors. However, the existing self-care advice was appreciated and contributed to an increased understanding of the situation. Comprehensible and easy-to-follow recommendations should be provided to all oesophageal cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Evidence-based self-care advice helpful for the individual oesophageal cancer survivor may be imperative to cope with the consequences of oesophagectomy after hospital discharge.

3.
Scand J Public Health ; 52(3): 336-344, 2024 May.
Article in English | MEDLINE | ID: mdl-38380520

ABSTRACT

AIM: We wanted to examine the impact of the Covid-19 pandemic on mental health in Danish school children in 5th to 7th grade (11 to 15 years), and whether the impact differed across age and sex. METHODS: We included 793 and 391 school children from winter 2020 and winter 2021, respectively. Mental health was measured using the Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS), Strengths and Difficulties Questionnaire (SDQ), and Brief Resilience Scale (BRS). Data were analyzed by sex using linear regression models adjusting for grade (age), cohabitation, geographical region, employment status of parents, and schools as clusters. RESULTS: Girls in 5th grade and boys in 6th grade during Covid-19 had statistically significant lower well-being (SWEMWBS) compared with before Covid-19. Girls in 5th and 6th grade during Covid-19 had non-statistically significant lower scores on all subscales of SDQ compared with girls before Covid-19. Girls in 7th grade during Covid-19 had statistically significant lower total difficulty score (SDQ) and fewer conduct problems (SDQ) compared with girls before Covid-19. Boys in 5th grade during Covid-19 had statistically significant fewer conduct problems (SDQ) compared with boys before Covid-19. CONCLUSIONS: This study indicates that the Covid-19 pandemic impacted Danish school children differently across sex and grade (age). During Covid-19, mental health tended to be better among the oldest girls and worse among the youngest girls compared with girls before Covid-19. Boys in 6th grade had poorer mental well-being, and boys in 5th grade had fewer conduct problems during Covid-19 compared with before Covid-19.


Subject(s)
COVID-19 , Mental Health , Humans , COVID-19/epidemiology , Denmark/epidemiology , Male , Female , Child , Adolescent , Schools , Students/psychology , Students/statistics & numerical data , Surveys and Questionnaires , Pandemics , Sex Factors
4.
Cancer Med ; 12(3): 3477-3487, 2023 02.
Article in English | MEDLINE | ID: mdl-36812121

ABSTRACT

BACKGROUND: The treatment of most esophageal cancer patients includes chemo(radio)therapy and extensive surgery, causing physical decline with loss of muscles. This trial aimed to test the hypothesis that a tailored home-based physical activity (PA) intervention improves muscle strength and mass in patients having undergone curative treatment for esophageal cancer. METHODS: Patients operated for esophageal cancer 1 year earlier were included in a nationwide randomized controlled trial in Sweden in 2016-2020. The intervention group was randomized to a 12-week home-based exercise program, while the control group was encouraged to maintain routine daily PA. The primary outcomes were changes in maximal/average hand grip strength measured with hand grip dynamometer and lower extremity strength measured using 30-second chair stand test and muscle mass measured using a portable bio-impedance analysis monitor. Intention-to-treat analysis was used, and results were presented as mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Among 161 randomized patients, 134 completed the study, 64 in the intervention group and 70 in the control group. Compared with the control group (MD 2.73; 95% CI 1.75-3.71), patients in the intervention group (MD 4.48; 95% CI 3.18-5.80) had statistically significantly (p = 0.03) improved lower extremity strength. No differences were seen for hand grip strength or muscle mass. CONCLUSION: A home-based PA intervention 1 year after surgery for esophageal cancer improves lower extremity muscle strength.


Subject(s)
Esophageal Neoplasms , Hand Strength , Humans , Exercise/physiology , Exercise Therapy/methods , Muscle Strength/physiology
5.
Ugeskr Laeger ; 184(15)2022 04 11.
Article in Danish | MEDLINE | ID: mdl-35410644

ABSTRACT

Cognitive sequelae of COVID-19 including memory and concentration difficulties have been observed in 40-65% of persons who have been hospitalised with COVID-19 and 27-50% of non-hospitalised individuals. The cognitive impairments are associated with reduced work function and quality of life. This review recommends systematic cognition screening at long-COVID clinics using brief and feasible objective cognitive screeners, such as the Screen for Cognitive Impairment in Psychiatry (SCIP) and Trail Making Test B or similar tests with sensitivity to cognitive impairment in young populations.


Subject(s)
COVID-19 , COVID-19/complications , Cognition , Humans , Neuropsychological Tests , Quality of Life , Post-Acute COVID-19 Syndrome
6.
Cell ; 185(6): 1025-1040.e14, 2022 03 17.
Article in English | MEDLINE | ID: mdl-35148837

ABSTRACT

During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination.


Subject(s)
Antibodies, Viral , BNT162 Vaccine , COVID-19 , Germinal Center , Antigens, Viral , COVID-19/prevention & control , Humans , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Vaccination
7.
Vaccines (Basel) ; 11(1)2022 Dec 20.
Article in English | MEDLINE | ID: mdl-36679852

ABSTRACT

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a different strain harboring the spike variant D614G. This case of reinfection was one of the first cases of reinfection reported in 2020. With antibody, B cell and T cell analytics, we show correlates of adaptive immunity at reinfection, including a differential response in neutralizing antibodies to a D614G pseudovirus. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.

8.
J Immunol ; 207(10): 2445-2455, 2021 11 15.
Article in English | MEDLINE | ID: mdl-34654689

ABSTRACT

Preterm labor (PTL) is the leading cause of neonatal morbidity and mortality worldwide. Whereas many studies have investigated the maternal immune responses that cause PTL, fetal immune cell activation has recently been raised as an important contributor to the pathogenesis of PTL. In this study, we analyzed lymphocyte receptor repertoires in maternal and cord blood from 14 term and 10 preterm deliveries, hypothesizing that the high prevalence of infection in patients with PTL may result in specific changes in the T cell and B cell repertoires. We analyzed TCR ß-chain (TCR-ß) and IgH diversity, CDR3 lengths, clonal sharing, and preferential usage of variable and joining gene segments. Both TCR-ß and IgH repertoires had shorter CDR3s compared with those in maternal blood. In cord blood samples, we found that CDR3 lengths correlated with gestational age, with shorter CDR3s in preterm neonates suggesting a less developed repertoire. Preterm cord blood displayed preferential usage of a number of genes. In preterm pregnancies, we observed significantly higher prevalence of convergent clones between mother/baby pairs than in term pregnancies. Together, our results suggest the repertoire of preterm infants displays a combination of immature features and convergence with maternal TCR-ß clones compared with that of term infants. The higher clonal convergence in PTL could represent mother and fetus both responding to a shared stimulus like an infection. These data provide a detailed analysis of the maternal-fetal immune repertoire in term and preterm patients and contribute to a better understanding of neonate immune repertoire development and potential changes associated with PTL.


Subject(s)
Immunoglobulin Heavy Chains/immunology , Infant, Newborn/immunology , Obstetric Labor, Premature/immunology , Premature Birth/immunology , Receptors, Antigen, T-Cell/immunology , Complementarity Determining Regions/immunology , Female , Humans , Infant, Premature/immunology , Pregnancy
9.
Eur J Oncol Nurs ; 54: 101983, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34333385

ABSTRACT

PURPOSE: Little is known about how patient's experience-based knowledge and advice after oesophageal cancer surgery may contribute to the understanding of how to improve HRQOL for future patients. In this study the advice that patients who were surgically treated for oesophageal cancer would like to share to future peers, based on their lived experiences were examined. METHOD: A qualitative inductive content analysis was used to analyse one open-ended question from 63 transcribed interviews performed during 2019, within the nationwide Swedish prospective cohort study OSCAR (Oesophageal Surgery on Cancer patients - Adaption and Recovery study). RESULTS: Patients had a broad range of advice to give from their experiences of oesophageal cancer surgery and recovery thereafter. Based on the analysis, three main categories were identified on the advice they wanted to pass on to future peers; health promoting advice, acknowledging the new situation, and advice on embracing support from others. The importance of being physically active, to maintain a positive mind set and to embrace support from both health care professionals as well as family and friends were central experiences that former patients wanted to share with their future peers. CONCLUSION: This study sheds a light on the experiences that patients who have undergone oesophageal cancer surgery have, and what advice they would give to future patients going through the same procedure. The analysis reveals that patients have a variety of advice from their experiences that they want to pass on to future patients. Further studies are needed in order to examine how these advice are received by and can benefit future patients, as well as the pathways of how peer advice is best communicated.


Subject(s)
Esophageal Neoplasms , Esophageal Neoplasms/surgery , Humans , Prospective Studies , Qualitative Research , Quality of Life , Sweden
10.
medRxiv ; 2021 Apr 07.
Article in English | MEDLINE | ID: mdl-33851181

ABSTRACT

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, new vaccine strategies including lipid nanoparticle delivery of antigen encoding RNA have been deployed globally. The BioNTech/Pfizer mRNA vaccine BNT162b2 encoding SARS-CoV-2 spike protein shows 95% efficacy in preventing disease, but it is unclear how the antibody responses to vaccination differ from those generated by infection. Here we compare the magnitude and breadth of antibodies targeting SARS-CoV-2, SARS-CoV-2 variants of concern, and endemic coronaviruses, in vaccinees and infected patients. We find that vaccination differs from infection in the dominance of IgG over IgM and IgA responses, with IgG reaching levels similar to those of severely ill COVID-19 patients and shows decreased breadth of the antibody response targeting endemic coronaviruses. Viral variants of concern from B.1.1.7 to P.1 to B.1.351 form a remarkably consistent hierarchy of progressively decreasing antibody recognition by both vaccinees and infected patients exposed to Wuhan-Hu-1 antigens.

11.
Science ; 372(6543): 738-741, 2021 05 14.
Article in English | MEDLINE | ID: mdl-33846272

ABSTRACT

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated pediatric and adult blood and deceased adult organ donor tissues to determine convergent antigen-specific antibody genes of similar sequences shared between individuals. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults had higher clone frequencies and greater class switching in lymphoid tissues than blood, while pediatric blood had abundant class-switched convergent clones. Consistent with reported serology, prepandemic children had class-switched convergent clones to severe acute respiratory syndrome coronavirus 2 with weak cross-reactivity to other coronaviruses, while adult blood or tissues showed few such clones. These results highlight the prominence of early childhood B cell clonal expansions and cross-reactivity for future responses to novel pathogens.


Subject(s)
Antibodies, Viral/immunology , B-Lymphocytes/immunology , Coronavirus/immunology , Immunologic Memory , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Aging , Child, Preschool , Cross Reactions , Ebolavirus/immunology , Female , Fetal Blood/immunology , Genes, Immunoglobulin , Humans , Immunoglobulin Class Switching , Immunoglobulin D/genetics , Immunoglobulin D/immunology , Immunoglobulin Heavy Chains/immunology , Immunoglobulin M/genetics , Immunoglobulin M/immunology , Infant , Lymph Nodes/immunology , Male , Middle Aged , Receptors, Antigen, B-Cell/immunology , Somatic Hypermutation, Immunoglobulin , Spleen/immunology , Young Adult
12.
Nurse Educ ; 46(2): 116-120, 2021.
Article in English | MEDLINE | ID: mdl-32511116

ABSTRACT

BACKGROUND: Nurse educators are challenged to ensure clinical education meets the changing health care environments and needs. PROBLEM: New nurses remain unprepared for practice, have insufficient foundational leadership capacities, and lack systems-thinking awareness. APPROACH: Responding to educational gaps, increased enrollment, and scarce clinical placements, faculty used an eclectic education model to develop a new capstone leadership clinical course that included 5 types of experiences. The total acute care clinical hours were reduced, while adding leadership-focused experiences and simulated learning. OUTCOMES: Stakeholders' evaluations indicate the pilot provided opportunities to strengthen students' leadership capacity, systems thinking, and professional identity while still providing sufficient practice managing care of multiple patients, engaging in teamwork, and applying evidence. CONCLUSION: The new clinical course addressed students' transition into practice needs and enrollment capacity issues. Thoughtful planning by invested stakeholders, communication among faculty, and clear expectations are necessary to implement eclectic clinical models.


Subject(s)
Curriculum , Education, Nursing , Leadership , Students, Nursing , Education, Nursing/organization & administration , Humans , Nursing Education Research , Students, Nursing/psychology
13.
medRxiv ; 2020 Sep 25.
Article in English | MEDLINE | ID: mdl-32995830

ABSTRACT

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a new strain harboring the spike variant D614G. With antibody and B cell analytics, we show correlates of adaptive immunity, including a differential response to D614G. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.

14.
Cell Host Microbe ; 28(4): 516-525.e5, 2020 10 07.
Article in English | MEDLINE | ID: mdl-32941787

ABSTRACT

B cells are critical for the production of antibodies and protective immunity to viruses. Here we show that patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) display early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify convergence of antibody sequences across SARS-CoV-2-infected patients, highlighting stereotyped naive responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and SARS-CoV.


Subject(s)
Antibodies, Viral/immunology , B-Lymphocytes/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/genetics , Antibody Formation , Betacoronavirus/genetics , COVID-19 , Female , HEK293 Cells , Humans , Immunogenetics , Immunoglobulin A/genetics , Immunoglobulin A/immunology , Immunoglobulin G/genetics , Immunoglobulin G/immunology , Male , Middle Aged , Pandemics , SARS-CoV-2 , Sequence Analysis , Spike Glycoprotein, Coronavirus/immunology
15.
Res Sq ; 2020 May 06.
Article in English | MEDLINE | ID: mdl-32702737

ABSTRACT

During virus infection B cells are critical for the production of antibodies and protective immunity. Establishment of a diverse antibody repertoire occurs by rearrangement of germline DNA at the immunoglobulin heavy and light chain loci to encode the membrane-bound form of antibodies, the B cell antigen receptor. Little is known about the B cells and antigen receptors stimulated by the novel human coronavirus SARS-CoV-2. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of V genes, and extensive activation of IgG and IgA subclasses without significant somatic mutation. We detect expansion of B cell clones as well as convergent antibodies with highly similar sequences across SARS-CoV-2 patients, highlighting stereotyped naïve responses to this virus. A shared convergent B cell clonotype in SARS-CoV-2 infected patients was previously seen in patients with SARS. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and other zoonotic spillover coronaviruses.

16.
bioRxiv ; 2020 Jul 09.
Article in English | MEDLINE | ID: mdl-32676593

ABSTRACT

During virus infection B cells are critical for the production of antibodies and protective immunity. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify extensive convergence of antibody sequences across SARS-CoV-2 patients, highlighting stereotyped naïve responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and other zoonotic spillover coronaviruses.

17.
J Prof Nurs ; 36(3): 106-110, 2020.
Article in English | MEDLINE | ID: mdl-32527630

ABSTRACT

This paper describes a three-semester hour applied research course taught over three semesters in a revamped PhD research curriculum at a Midwestern high research activity (R2) university-based nursing program. Faculty developed this strategy to help students become adequately prepared nurse scientists. Students and faculty engaged in a collaborative research project to provide students with opportunities to develop, integrate, and apply research knowledge, skills, and attitudes while concurrently advancing through the related research courses. A summary of these experiences and what was learned is organized within a knowledge, skills, and attitudes (KSA) framework. The collaboration between faculty and student peers was essential to students' success in the course. Student and faculty perspectives were used to describe what was learned during the first year this course was taught, together with future recommendations.


Subject(s)
Faculty, Nursing , Health Knowledge, Attitudes, Practice , Nursing Research , Research Design , Students, Nursing , Curriculum , Education, Nursing, Graduate , Humans
18.
Sci Immunol ; 5(45)2020 03 06.
Article in English | MEDLINE | ID: mdl-32139586

ABSTRACT

B cells in human food allergy have been studied predominantly in the blood. Little is known about IgE+ B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE+ clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing. IgE+ cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell phenotype. Clonally related IgE+ and non-IgE-expressing cell frequencies in tissues suggest local isotype switching, including transitions between IgA and IgE isotypes. Highly similar antibody sequences specific for peanut allergen Ara h 2 are shared between patients, indicating that common immunoglobulin genetic rearrangements may contribute to pathogenesis. These data define the gastrointestinal tract as a reservoir of IgE+ B lineage cells in food allergy.


Subject(s)
2S Albumins, Plant/immunology , Antigens, Plant/immunology , B-Lymphocytes/immunology , Gastrointestinal Tract/immunology , Immunoglobulin E/immunology , Peanut Hypersensitivity/immunology , Adult , Female , High-Throughput Nucleotide Sequencing , Humans , Immobilized Nucleic Acids/analysis , Immobilized Nucleic Acids/immunology , Male , Middle Aged
19.
Ugeskr Laeger ; 181(45)2019 Nov 04.
Article in Danish | MEDLINE | ID: mdl-31791452

ABSTRACT

Many patients with affective disorders have cognitive impairments during remission, which impede their functional recovery and quality of life. The International Society for Bipolar Disorders Targeting Cognition Task Force recommends that clinicians screen for cognitive impairments, when patients are in remission using subjective and objective screening tools. Clinicians should evaluate, whether any impairments are secondary to comorbidity, medication or unhealthy lifestyle. Information to patients and their relatives about how to tackle cognitive impairments can improve daily life functioning.


Subject(s)
Cognition Disorders , Cognitive Dysfunction , Mood Disorders , Cognition , Cognition Disorders/complications , Cognition Disorders/diagnosis , Cognition Disorders/therapy , Humans , Mood Disorders/complications , Neuropsychological Tests , Quality of Life
20.
Cell ; 177(6): 1566-1582.e17, 2019 05 30.
Article in English | MEDLINE | ID: mdl-31104840

ABSTRACT

Ebola virus (EBOV) remains a public health threat. We performed a longitudinal study of B cell responses to EBOV in four survivors of the 2014 West African outbreak. Infection induced lasting EBOV-specific immunoglobulin G (IgG) antibodies, but their subclass composition changed over time, with IgG1 persisting, IgG3 rapidly declining, and IgG4 appearing late. Striking changes occurred in the immunoglobulin repertoire, with massive recruitment of naive B cells that subsequently underwent hypermutation. We characterized a large panel of EBOV glycoprotein-specific monoclonal antibodies (mAbs). Only a small subset of mAbs that bound glycoprotein by ELISA recognized cell-surface glycoprotein. However, this subset contained all neutralizing mAbs. Several mAbs protected against EBOV disease in animals, including one mAb that targeted an epitope under evolutionary selection during the 2014 outbreak. Convergent antibody evolution was seen across multiple donors, particularly among VH3-13 neutralizing antibodies specific for the GP1 core. Our study provides a benchmark for assessing EBOV vaccine-induced immunity.


Subject(s)
Antibodies, Monoclonal/immunology , B-Lymphocytes/physiology , Hemorrhagic Fever, Ebola/immunology , Adult , Amino Acid Sequence/genetics , Animals , Antibodies, Monoclonal/isolation & purification , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , B-Lymphocytes/metabolism , Chlorocebus aethiops , Ebola Vaccines/immunology , Ebolavirus/genetics , Ebolavirus/metabolism , Ebolavirus/pathogenicity , Epitopes/blood , Female , Glycoproteins/genetics , Hemorrhagic Fever, Ebola/metabolism , Hemorrhagic Fever, Ebola/virology , Humans , Immunoglobulin G/immunology , Jurkat Cells , Longitudinal Studies , Male , Mice , Mice, Inbred BALB C , Survivors , Vero Cells , Viral Envelope Proteins/genetics
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