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Immune repertoire fingerprinting by principal component analysis reveals shared features in subject groups with common exposures.
Sevy AM, Soto C, Bombardi RG, Meiler J, Crowe JE
(2019) BMC Bioinformatics 20: 629
MeSH Terms: Adult, Antibodies, Cohort Studies, Fetal Blood, HIV Infections, High-Throughput Nucleotide Sequencing, Humans, Influenza, Human, Middle Aged, Principal Component Analysis, Vaccination
Show Abstract · Added March 21, 2020
BACKGROUND - Advances in next-generation sequencing (NGS) of antibody repertoires have led to an explosion in B cell receptor sequence data from donors with many different disease states. These data have the potential to detect patterns of immune response across populations. However, to this point it has been difficult to interpret such patterns of immune response between disease states in the absence of functional data. There is a need for a robust method that can be used to distinguish general patterns of immune responses at the antibody repertoire level.
RESULTS - We developed a method for reducing the complexity of antibody repertoire datasets using principal component analysis (PCA) and refer to our method as "repertoire fingerprinting." We reduce the high dimensional space of an antibody repertoire to just two principal components that explain the majority of variation in those repertoires. We show that repertoires from individuals with a common experience or disease state can be clustered by their repertoire fingerprints to identify common antibody responses.
CONCLUSIONS - Our repertoire fingerprinting method for distinguishing immune repertoires has implications for characterizing an individual disease state. Methods to distinguish disease states based on pattern recognition in the adaptive immune response could be used to develop biomarkers with diagnostic or prognostic utility in patient care. Extending our analysis to larger cohorts of patients in the future should permit us to define more precisely those characteristics of the immune response that result from natural infection or autoimmunity.
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MeSH Terms
Influenza H7N9 Virus Neuraminidase-Specific Human Monoclonal Antibodies Inhibit Viral Egress and Protect from Lethal Influenza Infection in Mice.
Gilchuk IM, Bangaru S, Gilchuk P, Irving RP, Kose N, Bombardi RG, Thornburg NJ, Creech CB, Edwards KM, Li S, Turner HL, Yu W, Zhu X, Wilson IA, Ward AB, Crowe JE
(2019) Cell Host Microbe 26: 715-728.e8
MeSH Terms: Animals, Antibodies, Heterophile, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Birds, Epitopes, Humans, Influenza A Virus, H7N9 Subtype, Influenza Vaccines, Influenza in Birds, Influenza, Human, Mice, Neuraminidase, Orthomyxoviridae Infections, Pre-Exposure Prophylaxis, Vaccination, Vaccines, Inactivated, Viral Proteins, Virus Release
Show Abstract · Added March 31, 2020
H7N9 avian influenza virus causes severe infections and might have the potential to trigger a major pandemic. Molecular determinants of human humoral immune response to N9 neuraminidase (NA) proteins, which exhibit unusual features compared with seasonal influenza virus NA proteins, are ill-defined. We isolated 35 human monoclonal antibodies (mAbs) from two H7N9 survivors and two vaccinees. These mAbs react to NA in a subtype-specific manner and recognize diverse antigenic sites on the surface of N9 NA, including epitopes overlapping with, or distinct from, the enzyme active site. Despite recognizing multiple antigenic sites, the mAbs use a common mechanism of action by blocking egress of nascent virions from infected cells, thereby providing an antiviral prophylactic and therapeutic protection in vivo in mice. Studies of breadth, potency, and diversity of antigenic recognition from four subjects suggest that vaccination with inactivated adjuvanted vaccine induce NA-reactive responses comparable to that of H7N9 natural infection.
Copyright © 2019 Elsevier Inc. All rights reserved.
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20 MeSH Terms
Immune-mediated adverse reactions to vaccines.
Stone CA, Rukasin CRF, Beachkofsky TM, Phillips EJ
(2019) Br J Clin Pharmacol 85: 2694-2706
MeSH Terms: Guillain-Barre Syndrome, Humans, Hypersensitivity, Delayed, Hypersensitivity, Immediate, Immunocompromised Host, Immunoglobulin E, Skin Tests, T-Lymphocytes, Vaccination, Vaccine Excipients, Vaccines
Show Abstract · Added March 30, 2020
Vaccination continues to be the single most important and successful public health intervention, due to its prevention of morbidity and mortality from prevalent infectious diseases. Severe immunologically mediated reactions are rare and less common with the vaccine than the true infection. However, these events can cause public fearfulness and loss of confidence in the safety of vaccination. In this paper, we perform a systematic literature search and narrative review of immune-mediated vaccine adverse events and their known and proposed mechanisms, and outline directions for future research. Improving our knowledge base of severe immunologically mediated vaccine reactions and their management drives better vaccine safety and efficacy outcomes.
© 2019 The British Pharmacological Society.
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11 MeSH Terms
Human papillomavirus vaccination completion rates among gynecological providers: an institutional retrospective review.
Elsamadicy EA, Schneiter MK, Hull PC, Khabele D
(2019) Hum Vaccin Immunother 15: 1851-1855
MeSH Terms: Adult, Female, Gynecology, Health Knowledge, Attitudes, Practice, Humans, Papillomavirus Infections, Papillomavirus Vaccines, Patient Acceptance of Health Care, Physicians, Practice Patterns, Physicians', Retrospective Studies, Vaccination, Young Adult
Show Abstract · Added July 11, 2019
: The primary aim of this study is to assess and characterize correlates of human papillomavirus (HPV) vaccine series completion among young adult women evaluated by gynecological (GYN) providers at a single institution and to measure changes over 4-y period. : At a major academic center, the medical records of 845 women administered the HPV vaccine series by a GYN provider were retrospectively reviewed from 2006 to 2010 and 2014 to 2015. Patients were grouped based on the date of vaccine initiation into "earlier" (2006-2010) and "later" (2014-2015) cohorts. Patient demographics, dates of vaccine administration, and practice locations where vaccines were administered were collected. Patients who received all 3 vaccines within 6 months were deemed "complete". Patients seen by a provider but did not receive the vaccination were deemed "missed opportunities". The primary outcome was completion of HPV vaccination according to the ACIP guidelines. : The 845 patients were divided into earlier (n = 399) and later (n = 446) cohorts. There was no statistically significant difference in completion rates between the earlier-cohort compared to the later-cohort (). Age at initiation were similar (), with the complete cohort having a significantly lower body mass index (BMI) than the incomplete cohort (). There was a significant difference between the completion rates among race/ethnic groups ( = .036). African-American and Hispanic ( patient-populations had the lowest completion rates and higher missed opportunities. : Our study found an overall low completion rate in both earlier and later cohorts. Additionally, higher BMI and African-American and Hispanic race/ethnicity were associated with low vaccine completion.
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13 MeSH Terms
Influenza vaccination and myocarditis among patients receiving immune checkpoint inhibitors.
Awadalla M, Golden DLA, Mahmood SS, Alvi RM, Mercaldo ND, Hassan MZO, Banerji D, Rokicki A, Mulligan C, Murphy SPT, Jones-O'Connor M, Cohen JV, Heinzerling LM, Armanious M, Sullivan RJ, Damrongwatanasuk R, Chen CL, Gupta D, Kirchberger MC, Moslehi JJ, Shah SP, Ganatra S, Thavendiranathan P, Rizvi MA, Sahni G, Lyon AR, Tocchetti CG, Mercurio V, Thuny F, Ederhy S, Mahmoudi M, Lawrence DP, Groarke JD, Nohria A, Fradley MG, Reynolds KL, Neilan TG
(2019) J Immunother Cancer 7: 53
MeSH Terms: Aged, Aged, 80 and over, Antineoplastic Agents, Immunological, Female, Humans, Influenza Vaccines, Influenza, Human, Male, Middle Aged, Myocarditis, Neoplasms, Registries, Vaccination
Show Abstract · Added February 24, 2019
BACKGROUND - Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs.
METHODS - Patients on ICIs who developed myocarditis (n = 101) (cases) were compared to ICI-treated patients (n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death.
RESULTS - The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002).
CONCLUSION - The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV.
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13 MeSH Terms
Antibody Determinants of Influenza Immunity.
Crowe JE
(2019) J Infect Dis 219: S21-S29
MeSH Terms: Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Antigens, Viral, B-Lymphocytes, Cross Reactions, Genetic Drift, Hemagglutinin Glycoproteins, Influenza Virus, Humans, Immunologic Memory, Influenza A virus, Influenza Vaccines, Influenza, Human, Neuraminidase, Point Mutation, Vaccination, Vaccines, Inactivated
Show Abstract · Added March 31, 2019
Understanding antigenic variation in influenza virus strains and how the human immune system recognizes strains are central challenges for vaccinologists. Antibodies directed to the 2 major viral surface membrane proteins, hemagglutinin (HA) and neuraminidase (NA), mediate protection against reinfection following natural infection or vaccination, but HA and NA protein sequences in field strains are highly variable. The central questions are how to achieve protective antibody responses in a higher proportion of individuals and how to induce responses with more breadth and durability. Studies using isolation of human monoclonal antibodies followed by structural and functional characterization revealed conserved antigenic sites recognized by broadly cross-reactive antibodies. The antigenic landscape on HA and NA proteins is coming into focus to inform studies of the correlates and mechanisms of immunity. Understanding the antibody determinants of influenza immunity points the way toward development and testing of next-generation vaccines with potential to confer broadly protective immunity.
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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17 MeSH Terms
Structural basis of a potent human monoclonal antibody against Zika virus targeting a quaternary epitope.
Long F, Doyle M, Fernandez E, Miller AS, Klose T, Sevvana M, Bryan A, Davidson E, Doranz BJ, Kuhn RJ, Diamond MS, Crowe JE, Rossmann MG
(2019) Proc Natl Acad Sci U S A 116: 1591-1596
MeSH Terms: Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Cryoelectron Microscopy, Disease Models, Animal, Epitopes, Humans, Male, Mice, Mice, Inbred C57BL, Vaccination, Viral Envelope Proteins, Zika Virus, Zika Virus Infection
Show Abstract · Added March 31, 2019
Zika virus (ZIKV) is a major human pathogen and member of the genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and from mother to fetus in humans. During recent outbreaks, ZIKV infections have been linked to microcephaly, congenital disease, and Guillain-Barré syndrome. Neutralizing antibodies have potential as therapeutic agents. We report here a 4-Å-resolution cryo-electron microscopy structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195. The footprint of the ZIKV-195 Fab fragment expands across two adjacent envelope (E) protein protomers. ZIKV neutralization by this antibody is presumably accomplished by cross-linking the E proteins, which likely prevents formation of E protein trimers required for fusion of the viral and cellular membranes. A single dose of ZIKV-195 administered 5 days after virus inoculation showed marked protection against lethality in a stringent mouse model of infection.
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Current Understanding of Humoral Immunity to Enterovirus D68.
Vogt MR, Crowe JE
(2018) J Pediatric Infect Dis Soc 7: S49-S53
MeSH Terms: Animals, Antibodies, Neutralizing, Disease Models, Animal, Enterovirus D, Human, Enterovirus Infections, Epitopes, Humans, Immunity, Humoral, Nervous System Diseases, Respiratory Tract Infections, Seroepidemiologic Studies, Vaccination, Viral Vaccines
Show Abstract · Added March 31, 2019
Enterovirus D68 (EV-D68) is a pathogen that causes outbreaks of respiratory illness across the world, mostly in children, and can be especially severe in those with asthma. Clusters of acute flaccid myelitis, a poliomyelitis-like neuromuscular weakness syndrome, often occur concurrent with EV-D68 respiratory outbreaks. Seroepidemiologic studies have found that the serum of nearly everyone older than 2 to 5 years contains anti-EV-D68 neutralizing antibodies, which suggests that EV-D68 is a ubiquitous pathogen of childhood. However, knowledge of the viral epitopes against which the humoral immune response is directed is only inferred from previous studies of related viruses. Although neutralizing antibodies protect newborn mice from lethal EV-D68 inoculation via nonphysiologic routes, cotton rats have a mixed phenotype of both benefit and possible exacerbation when inoculated intranasally. The human antibody response to EV-D68 needs to be studied further to clarify the role of antibodies in protection versus pathogenesis, which might differ among respiratory and neurologic disease phenotypes.
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Survivorship, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.
Denlinger CS, Sanft T, Baker KS, Broderick G, Demark-Wahnefried W, Friedman DL, Goldman M, Hudson M, Khakpour N, King A, Koura D, Lally RM, Langbaum TS, McDonough AL, Melisko M, Montoya JG, Mooney K, Moslehi JJ, O'Connor T, Overholser L, Paskett ED, Peppercorn J, Pirl W, Rodriguez MA, Ruddy KJ, Silverman P, Smith S, Syrjala KL, Tevaarwerk A, Urba SG, Wakabayashi MT, Zee P, McMillian NR, Freedman-Cass DA
(2018) J Natl Compr Canc Netw 16: 1216-1247
MeSH Terms: Anthracyclines, Antibiotics, Antineoplastic, Antineoplastic Agents, Immunological, Bacterial Infections, Cancer Survivors, Cardiotoxicity, Humans, Immunocompromised Host, Lymphedema, Mass Screening, Medical Oncology, Neoplasms, Risk Assessment, Societies, Medical, Survivorship, United States, Vaccination, Virus Diseases
Show Abstract · Added December 13, 2018
The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period. This portion of the guidelines describes recommendations regarding the management of anthracycline-induced cardiotoxicity and lymphedema. In addition, recommendations regarding immunizations and the prevention of infections in cancer survivors are included.
Copyright © 2018 by the National Comprehensive Cancer Network.
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18 MeSH Terms
Anaphylaxis after vaccination in a pediatric patient: further implicating alpha-gal allergy.
Stone CA, Commins SP, Choudhary S, Vethody C, Heavrin JL, Wingerter J, Hemler JA, Babe K, Phillips EJ, Norton AE
(2019) J Allergy Clin Immunol Pract 7: 322-324.e2
MeSH Terms: Allergens, Anaphylaxis, Angioedema, Animals, Cattle, Chickenpox Vaccine, Child, Preschool, Dyspnea, Food Hypersensitivity, Gelatin, Humans, Immunoglobulin E, Male, Mass Vaccination, Measles-Mumps-Rubella Vaccine, Skin Tests, Urticaria
Added March 30, 2020
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17 MeSH Terms