Digital Commons Network^™

Hippocampus Guides Adaptive Learning During Dynamic Social Interactions, Oriel Feldmanhall, David F. Montez, Elizabeth A. Phelps, Lila Davachi, Vishnu P. Murty

Open Access Publications

How do we evaluate whether someone will make a good friend or collaborative peer? A hallmark of human cognition is the ability to make adaptive decisions based on information garnered from limited prior experiences. Using an interactive social task measuring adaptive choice (deciding who to reengage or avoid) in male and female participants, we find the hippocampus supports value-based social choices following single-shot learning. These adaptive choices elicited a suppression signal in the hippocampus, revealing sensitivity for the subjective perception of a person and how well they treat you during choice. The extent to which the hippocampus was suppressed was …

Trim67 Regulates Exocytic Mode And Neuronal Morphogenesis Via Snap47, Fabio L Urbina, Shalini Menon, Dennis Goldfarb, Reginald Edwards, M Ben Major, Patrick Brennwald, Stephanie L Gupton

Open Access Publications

Neuronal morphogenesis involves dramatic plasma membrane expansion, fueled by soluble N-ethylmaleimide-sensitive factor attachment protein eceptors (SNARE)-mediated exocytosis. Distinct fusion modes described at synapses include full-vesicle fusion (FVF) and kiss-and-run fusion (KNR). During FVF, lumenal cargo is secreted and vesicle membrane incorporates into the plasma membrane. During KNR, a transient fusion pore secretes cargo but closes without membrane addition. In contrast, fusion modes are not described in developing neurons. Here, we resolve individual exocytic events in developing murine cortical neurons and use classification tools to identify four distinguishable fusion modes: two FVF-like modes that insert membrane material and two KNR-like modes …

Rates Of Gene Conversions Between Escherichia Coli Ribosomal Operons, Isaac Gifford, Aurko Dasgupta, Jeffrey E Barrick

Open Access Publications

Due to their universal presence and high sequence conservation, ribosomal RNA (rRNA) sequences are used widely in phylogenetics for inferring evolutionary relationships between microbes and in metagenomics for analyzing the composition of microbial communities. Most microbial genomes encode multiple copies of rRNA genes to supply cells with sufficient capacity for protein synthesis. These copies typically undergo concerted evolution that keeps their sequences identical, or nearly so, due to gene conversion, a type of intragenomic recombination that changes one copy of a homologous sequence to exactly match another. Widely varying rates of rRNA gene conversion have previously been estimated by comparative …

Controlling Opioid Receptor Functional Selectivity By Targeting Distinct Subpockets Of The Orthosteric Site, Rajendra Uprety, Tao Che, Balázs R. Varga, Abdelfattah Faouzi, Sarah M. Bernhard, Susruta Majumdar, Et Al

Open Access Publications

Controlling receptor functional selectivity profiles for opioid receptors is a promising approach for discovering safer analgesics; however, the structural determinants conferring functional selectivity are not well understood. Here, we used crystal structures of opioid receptors, including the recently solved active state kappa opioid complex with

Treatment Of Patients With Chronic Pruritus Of Unknown Origin With Dupilumab, Jiehyun Jeon, Fang Wang, Asima Badic, Brian S Kim

Open Access Publications

BACKGROUND: Chronic pruritus of unknown origin (CPUO) is a highly debilitating disease that lacks effective treatments. This study explores a new therapeutic strategy with dupilumab.

OBJECTIVES: To examine whether patients with CPUO demonstrate clinical response to dupilumab.

PATIENTS AND METHODS: This is a retrospective case series examining all patients with CPUO who were treated with dupilumab from March 2017 to December 2019 at a tertiary referral clinic at Washington University School of Medicine in St. Louis, MO. Numerical rating scale (NRS) itch score changes over time were recorded and analyzed.

RESULTS: Fifteen patients (67% women; mean [SD] age, 68.7 [12.6] …

Sympathetic Stimulation Increases Serum Lactate Concentrations In Patients Admitted With Sepsis: Implications For Resuscitation Strategies, Nikhil Jagan, Lee E Morrow, Ryan W Walters, Robert W Plambeck, Tej M Patel, Douglas R Moore, Mark A Malesker

Open Access Publications

BACKGROUND: Diametrically opposed positions exist regarding the deleterious effects of elevated lactate. There are data suggesting that it is a detrimental proxy for tissue hypoperfusion and anaerobic metabolism in sepsis and an alternative viewpoint is that some of the hyperlactatemia produced maybe adaptive. This study was conducted to explore the relationship between serum lactate levels, mean arterial blood pressure (MAP), and sympathetic stimulation in patients with sepsis.

METHODS: Retrospective analysis of prospectively collected clinical data from four community-based hospitals and one academic medical center. 8173 adults were included. Heart rate (HR) was used as a surrogate marker of sympathetic stimulation. …

Biomarkers Associated With Blinatumomab Outcomes In Acute Lymphoblastic Leukemia, Andrew H Wei, Josep-Maria Ribera, Richard A Larson, David Ritchie, Armin Ghobadi, Yuqi Chen, Abraham Anderson, Cedric E Dos Santos, Janet Franklin, Hagop Kantarjian

Open Access Publications

This study aimed to identify biomarkers for clinical outcomes in a phase 3 clinical study of blinatumomab or chemotherapy in adults with Philadelphia chromosome-negative relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Patients were randomized 2:1 to receive blinatumomab, a BiTE

Seroprevalence Of Sars-Cov-2 Antibodies In Children And Adults In St. Louis, Missouri, Usa, Brittany K Smith, Andrew B Janowski, Jonathan E Danis, Ian B Harvey, Haiyan Zhao, Ya-Nan Dai, Christopher W Farnsworth, Ann M Gronowski, Stephen Roper, Daved H Fremont, David Wang

Open Access Publications

Reported coronavirus disease 2019 (COVID-19) case counts likely underestimate the true prevalence because mild or asymptomatic cases often go untested. Here, we use a sero-survey to estimate the seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the St. Louis, MO, metropolitan area in a symptom-independent manner. Five hundred three adult and 555 pediatric serum/plasma samples were collected from patients presenting to Barnes-Jewish Hospital or St. Louis Children's Hospital between 14 April 2020 and 12 May 2020. We developed protocols for in-house enzyme-linked immunosorbent assays (ELISAs) using spike and nucleoprotein and used the assays to estimate …

Gut Helicobacter Presentation By Multiple Dendritic Cell Subsets Enables Context-Specific Regulatory T Cell Generation, Emilie V. Russler-Germain, Jaeu Yi, Shannon Young, Katherine Nutsch, Harikesh S. Wong, Teresa L. Ai, Jiani N. Chai, Vivek Durai, Daniel H. Kaplan, Ronald N. Germain, Kenneth M. Murphy, Chyi-Song Hsieh

Open Access Publications

Generation of tolerogenic peripheral regulatory T (pTreg) cells is commonly thought to involve CD103

Enhanced Efficacy And Increased Long-Term Toxicity Of Cns-Directed, Aav-Based Combination Therapy For Krabbe Disease, Yedda Li, Christopher A Miller, Lauren K Shea, Xuntian Jiang, Miguel A Guzman, Randy J Chandler, Sai M Ramakrishnan, Stephanie N Smith, Charles P Venditti, Carole A Vogler, Daniel S Ory, Timothy J Ley, Mark S Sands

Open Access Publications

Infantile globoid cell leukodystrophy (GLD, Krabbe disease) is a demyelinating disease caused by the deficiency of the lysosomal enzyme galactosylceramidase (GALC) and the progressive accumulation of the toxic metabolite psychosine. We showed previously that central nervous system (CNS)-directed, adeno-associated virus (AAV)2/5-mediated gene therapy synergized with bone marrow transplantation and substrate reduction therapy (SRT) to greatly increase therapeutic efficacy in the murine model of Krabbe disease (Twitcher). However, motor deficits remained largely refractory to treatment. In the current study, we replaced AAV2/5 with an AAV2/9 vector. This single change significantly improved several endpoints primarily associated with motor function. However, nearly all …

Satb2 Induction Of A Neural Crest Mesenchyme-Like Program Drives Melanoma Invasion And Drug Resistance, Maurizio Fazio, Charles K. Kaufman, Et Al

Open Access Publications

Recent genomic and scRNA-seq analyses of melanoma demonstrated a lack of recurrent genetic drivers of metastasis, while identifying common transcriptional states correlating with invasion or drug resistance. To test whether transcriptional adaptation can drive melanoma progression, we made use of a zebrafish mitfa:

The Role Of Endometrial Sampling For Surveillance Of Recurrence In Postmenopausal Patients With Medically Inoperable Stage I Endometrial Cancer, Angelina Carey-Love, Mary M Mullen, Abigail Zamorano, Stephanie Markovina, Andrea R Hagemann, Katherine C Fuh, Premal H Thaker, David G Mutch, Matthew A Powell, Lindsay M Kuroki

Open Access Publications

It is unclear if surveillance for postmenopausal women with medically inoperable stage 1 endometrial cancer (EC) should differ depending on their management strategy. Thus, we investigated the utility of surveillance endometrial sampling among 53 postmenopausal women with medically inoperable, clinical stage I, grade 1 endometrioid EC who received either progestin therapy or radiation between 2009 and 2018, at a single academic institution. Frequency and results of endometrial sampling, as well as recurrence and survival rates were studied. Of 53 patients, 18 (34.0%) received progestin therapy and 35 (66.0%) radiation. Medically managed patients were treated with megestrol acetate (27.7%), a levonorgestrel …

Polygenic Burden Has Broader Impact On Health, Cognition, And Socioeconomic Outcomes Than Most Rare And High-Risk Copy Number Variants, Elmo Christian Saarentaus, Lei Chen, Ira M Hall, Et Al

Open Access Publications

Copy number variants (CNVs) are associated with syndromic and severe neurological and psychiatric disorders (SNPDs), such as intellectual disability, epilepsy, schizophrenia, and bipolar disorder. Although considered high-impact, CNVs are also observed in the general population. This presents a diagnostic challenge in evaluating their clinical significance. To estimate the phenotypic differences between CNV carriers and non-carriers regarding general health and well-being, we compared the impact of SNPD-associated CNVs on health, cognition, and socioeconomic phenotypes to the impact of three genome-wide polygenic risk score (PRS) in two Finnish cohorts (FINRISK, n = 23,053 and NFBC1966, n = 4895). The focus was on …

Capsule Carbohydrate Structure Determines Virulence In Acinetobacter Baumannii, Yuli Talyansky, Travis B. Nielsen, Jun Yan, Ulrike Carlino-Macdonald, Gisela Di Venanzio, Somnath Chakravorty, Amber Ulhaq, Mario F. Feldman, Thomas A. Russo, Evgeny Vinogradov, Brian Luna, Meredith S. Wright, Mark D. Adams, Brad Spellberg

Open Access Publications

Acinetobacter baumannii is a highly antibiotic-resistant bacterial pathogen for which novel therapeutic approaches are needed. Unfortunately, the drivers of virulence in A. baumannii remain uncertain. By comparing genomes among a panel of A. baumannii strains we identified a specific gene variation in the capsule locus that correlated with altered virulence. While less virulent strains possessed the intact gene gtr6, a hypervirulent clinical isolate contained a spontaneous transposon insertion in the same gene, resulting in the loss of a branchpoint in capsular carbohydrate structure. By constructing isogenic gtr6 mutants, we confirmed that gtr6-disrupted strains were protected from phagocytosis in vitro and …

Quantitative Proteomic Analysis Of Diabetes Mellitus In Heart Failure With Preserved Ejection Fraction, Thomas C Hanff, Ali Javaheri, Et Al

Open Access Publications

Diabetes mellitus (DM) is associated with a higher risk of heart failure hospitalization and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Using SomaScan assays and proteomics analysis of plasma from participants in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial and the Penn Heart Failure Study, this study identified 10 proteins with significantly different expression in patients with HFpEF and DM. Of these, apolipoprotein M was found to mediate 72% (95% CI: 36% to 100%; p < 0.001) of the association between DM and the risk of cardiovascular death, aborted cardiac arrest, and heart failure hospitalization.

Liver Transplantation: Expanding The Donor And Recipient Pool, Ola Ahmed, M. B. Majella Doyle

Open Access Publications

Liver transplantation is an exemplar model of complex surgery and the only curative option for patients with end-stage liver disease. Although historically associated with poor outcomes, liver cancer management has also been revolutionised with liver transplantation and in some instances, survival outcomes are comparable to surgical resection. As such, the key elements underpinning the major advances in surgical technique, immunological therapies and allocation policies combined with improved patient and graft survival outcomes have created a huge demand for organ donation. Despite improvements in donor and recipient selection, there is a persistent disparity between organ supply and demand. Candidate wait-list mortality …

Prognostic And Predictive Effect Of Kras Gene Copy Number And Mutation Status In Early Stage Non-Small Cell Lung Cancer Patients, Andrea S. Fung, Maryam Karimi, Stefan Michiels, Lesley Seymour, Elisabeth Brambilla, Thierry Le-Chevalier, Jean-Charles Soria, Robert Kratzke, Stephen L. Graziano, Siddhartha Devarakonda, Ramaswamy Govindan, Ming-Sound Tsao, Frances A. Shepherd, Lace-Bio Collaborative Group

Open Access Publications

Background: In the current analysis, we characterize the prognostic significance of

Methods: Clinical and genomic data from the LACE (Lung Adjuvant Cisplatin Evaluation)-Bio consortium was utilized. CNAs were categorized as Gain (CN ≥2) or Neutral (Neut)/Loss;

Results: Of the 946 (399 adenocarcinoma) NSCLC patients, 41 [30] had MUT + Gain, 145 [99] MUT + Neut/Loss, 125 [16] WT + Gain, and 635 [254] WT + Neut/Loss. A non-significant trend towards worse lung cancer-specific survival (LCSS; HR =1.34; 95% CI, 0.83-2.17, P=0.232), DFS (HR =1.34; 95% CI, 0.86-2.09, P=0.202) and OS (HR =1.59; 95% CI, 0.99-2.54, P=0.055) was seen in

Conclusions: …

Suspected Metal Allergy And Femoral Loosening After Total Knee Arthroplasty: A Diagnostic Dilemma, Elizabeth G Lieberman, Robert L Barrack, Thomas P Schmalzried

Open Access Publications

Metal sensitivity is increasingly prevalent and is associated with negative outcomes after total knee arthroplasty (TKA). Currently, there is no consensus on diagnostic criteria for TKA failure from immune reaction. We present a patient who had pain and aseptic effusion 2 years after TKA. Radiographs were concerning femoral loosening. Lymphocyte transformation testing showed nickel sensitivity. During revision surgery, the femoral component was loose. The histologic aseptic lymphocyte-dominated vasculitis-associated lesion score was 4 with elevated CD4+ lymphocytes, consistent with sensitization. Nickel-free revision implants were used. One year after surgery, the patient is symptom-free. This case has features suggestive of an immune …

Evaluation Of Tumor Immunity After Administration Of Conditionally Replicative Adenoviral Vector In Canine Osteosarcoma Patients, Payal Agarwal, Elizabeth A Gammon, Maninder Sandey, Stephanie S Lindley, Jey W Koehler, Brad M Matz, Annette N Smith, Elena A Kashentseva, Igor P Dmitriev, David T Curiel, Bruce F Smith

Open Access Publications

Osteosarcoma is one among the most common neoplasms in dogs. Current treatments show limited efficacy and fail to prevent metastasis. Conditionally replicative adenoviruses (CRAd) replicate exclusively in targeted tumor cells and release new virus particles to infect additional cells. We proposed that OC-CAVE1 (CAV2 with the E1A promoter replaced with the osteocalcin promotor) may also enhance existing immunity against tumors by overcoming immune tolerance via exposure of new epitopes and cytokine signaling. Eleven client-owned dogs with spontaneously occurring osteosarcomas were enrolled in a pilot study. All dogs were injected with OC-CAVE1 following amputation of the affected limb or limb-sparing surgery. …

The Effect Of The Covid-19 Pandemic On Hip And Knee Arthroplasty Patients In The United States: A Multicenter Update To The Previous Survey, Timothy S Brown, Christopher A Anthony, Et Al

Open Access Publications

Background: In March 2020, elective total hip and knee arthroplasty (THA and TKA) were suspended across the United States in response to the COVID-19 pandemic. We had previously published the results of a survey to the affected patients from 6 institutions. We now present the results of a larger distribution of this survey, through May and June 2020, to electively scheduled patients representing different regions of the United States.

Methods: Fifteen centers identified through the American Association of Hip and Knee Surgeons Research Committee participated in a survey study of THA and TKA patients. Patients scheduled for primary elective THA …

Ccr5 Inhibition In Critical Covid-19 Patients Decreases Inflammatory Cytokines, Increases Cd8 T-Cells, And Decreases Sars-Cov2 Rna In Plasma By Day 14, Bruce K Patterson, Philip A Mudd, Et Al

Open Access Publications

OBJECTIVE: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global pandemic. Emerging results indicate a dysregulated immune response. Given the role of CCR5 in immune cell migration and inflammation, we investigated the impact of CCR5 blockade via the CCR5-specific antibody leronlimab on clinical, immunological, and virological parameters in severe COVID-19 patients.

METHODS: In March 2020, 10 terminally ill, critical COVID-19 patients received two doses of leronlimab via individual emergency use indication. We analyzed changes in clinical presentation, immune cell populations, inflammation, as well as SARS-CoV-2 plasma viremia before and 14 days after treatment.

RESULTS: Over the …

Flortaucipir (Tau) Pet In Lgi1 Antibody Encephalitis, Gregory S Day, Brian A Gordon, Austin Mccullough, Robert C Bucelli, Richard J Perrin, Tammie L S Benzinger, Beau M Ances

Open Access Publications

The contributors to persistent cognitive impairment and hippocampal atrophy in leucine-rich glioma-inactivated 1 antibody encephalitis (LGI1) patients are unknown. We evaluated whether tau neuropathology measured with [

Ana Webinars: Implementation Of A Conference-Based Virtual Networking Event, Bhooma Aravamuthan, Eric C Landsness, Elizabeth Silbermann

Open Access Publications

OBJECTIVE: To describe the design and implementation of a virtual network event at the American Neurological Association (ANA) annual meeting led by the Junior and Early Career Member (JECM) Committee.

METHODS: We designed a one-hour virtual networking session featuring three 15-minute small group meetings preceded and followed by general remarks. Each small group session consisted of one senior mentor, a junior/early career faculty moderator, and three to four junior/early career mentees. All participants completed an exit survey to evaluate perceived benefit of this event.

RESULTS: We recruited 103 mentees, 26 moderators, and 26 mentors for the event. Mentees were primarily …

Evaluating Cognitive Relationships With Resting-State And Task-Driven Blood Oxygen Level-Dependent Variability, Peter R Millar, Beau M Ances, Brian A Gordon, Tammie L S Benzinger, John C Morris, David A Balota

Open Access Publications

Recent functional magnetic resonance imaging studies have reported that moment-to-moment variability in the blood oxygen level-dependent (BOLD) signal is positively associated with task performance and, thus, may reflect a behaviorally sensitive signal. However, it is not clear whether estimates of resting-state and task-driven BOLD variability are differentially related to cognition, as they may be driven by distinct sources of variance in the BOLD signal. Moreover, other studies have suggested that age differences in resting-state BOLD variability may be particularly sensitive to individual differences in cardiovascular, rather than neural, factors. In this study, we tested relationships between measures of behavioral task …

Global, Cell Non-Autonomous Gene Regulation Drives Individual Lifespan Among Isogenic C. Elegans, Holly E. Kinser, Matthew C. Mosley, Isaac B. Plutzer, Zachary Pincus

Open Access Publications

Across species, lifespan is highly variable among individuals within a population. Even genetically identical

Progress Towards Onchocerciasis Elimination In Côte D'Ivoire: A Geospatial Modelling Study, Obiora A. Eneanya, Benjamin G. Koudou, Meite Aboulaye, Aba Ange Elvis, Yeo Souleymane, Marie-Madeleine Kouakou, Gary J. Weil, Peter U. Fischer

Open Access Publications

BACKGROUND: Côte d'Ivoire has had 45 years of intervention for onchocerciasis by vector control (from 1975 to 1991), ivermectin mass drug administration (MDA) (from 1992 to 1994) and community directed treatment with ivermectin (CDTi) from 1995 to the present. We modeled onchocerciasis endemicity during two time periods that correspond to the scale up of vector control and ivermectin distribution, respectively. This analysis illustrates progress towards elimination during these periods, and it has identified potential hotspots areas that are at risk for ongoing transmission.

METHODS AND FINDINGS: The analysis used Ministry of Health skin snip microfilaria (MF) prevalence and intensity data …

"It's Way More Than Just Writing A Prescription": A Qualitative Study Of Preferences For Integrated Versus Non-Integrated Treatment Models Among Individuals With Opioid Use Disorder, Elizabeth C Saunders, Sarah K Moore, Olivia Walsh, Stephen A Metcalf, Alan J Budney, Patricia Cavazos-Rehg, Emily Scherer, Lisa A Marsch

Open Access Publications

BACKGROUND: Increasingly, treatment for opioid use disorder (OUD) is offered in integrated treatment models addressing both substance use and other health conditions within the same system. This often includes offering medications for OUD in general medical settings. It remains uncertain whether integrated OUD treatment models are preferred to non-integrated models, where treatment is provided within a distinct treatment system. This study aimed to explore preferences for integrated versus non-integrated treatment models among people with OUD and examine what factors may influence preferences.

METHODS: This qualitative study recruited participants (n = 40) through Craigslist advertisements and flyers posted in treatment programs …

Mapping The Immune Environment In Clear Cell Renal Carcinoma By Single-Cell Genomics, Nicholas Borcherding, Ajaykumar Vishwakarma, Andrew P Voigt, Andrew Bellizzi, Jacob Kaplan, Kenneth Nepple, Aliasger K Salem, Russell W Jenkins, Yousef Zakharia, Weizhou Zhang

Open Access Publications

Clear cell renal cell carcinoma (ccRCC) is one of the most immunologically distinct tumor types due to high response rate to immunotherapies, despite low tumor mutational burden. To characterize the tumor immune microenvironment of ccRCC, we applied single-cell-RNA sequencing (SCRS) along with T-cell-receptor (TCR) sequencing to map the transcriptomic heterogeneity of 25,688 individual CD45

Metabolic Compensation Activates Pro-Survival Mtorc1 Signaling Upon 3-Phosphoglycerate Dehydrogenase Inhibition In Osteosarcoma, Richa Rathore, Katharine E Caldwell, Charles Schutt, Caitlyn B Brashears, Bethany C Prudner, William R Ehrhardt, Cheuk Hong Leung, Heather Lin, Najat C Daw, Hannah C Beird, Abigail Giles, Wei-Lien Wang, Alexander J Lazar, John S A Chrisinger, J Andrew Livingston, Brian A Van Tine

Open Access Publications

Osteosarcoma is the most common pediatric and adult primary malignant bone cancer. Curative regimens target the folate pathway, downstream of serine metabolism, with high-dose methotrexate. Here, the rate-limiting enzyme in the biosynthesis of serine from glucose, 3-phosphoglycerate dehydrogenase (PHGDH), is examined, and an inverse correlation between PHGDH expression and relapse-free and overall survival in osteosarcoma patients is found. PHGDH inhibition in osteosarcoma cell lines attenuated cellular proliferation without causing cell death, prompting a robust metabolic analysis to characterize pro-survival compensation. Using metabolomic and lipidomic profiling, cellular response to PHGDH inhibition is identified as accumulation of unsaturated lipids, branched chain amino …

Polyclonal Epitope Mapping Reveals Temporal Dynamics And Diversity Of Human Antibody Responses To H5n1 Vaccination, Julianna Han, Aaron J Schmitz, Sara T Richey, Ya-Nan Dai, Hannah L Turner, Bassem M Mohammed, Daved H Fremont, Ali H Ellebedy, Andrew B Ward

Open Access Publications

Novel influenza A virus (IAV) strains elicit recall immune responses to conserved epitopes, making them favorable antigenic choices for universal influenza virus vaccines. Evaluating these immunogens requires a thorough understanding of the antigenic sites targeted by the polyclonal antibody (pAb) response, which single-particle electron microscopy (EM) can sensitively detect. In this study, we employ EM polyclonal epitope mapping (EMPEM) to extensively characterize the pAb response to hemagglutinin (HA) after H5N1 immunization in humans. Cross-reactive pAbs originating from memory B cells immediately bound the stem of HA and persisted for more than a year after vaccination. In contrast, de novo pAb …