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  1. Article ; Online: Monitored COVID-19 vaccine humoral response in immunocompromised solid organ transplant recipients.

    Nikaein, Afzal / Chemmalakuzhy, Ashley / Khan, Salman / Hunt, Judson / Haumpy, Derek / Choudhary, Alok / Pinter, Abraham / Sanchez, Ayrton / Lerman, Mark

    Human immunology

    2024  Volume 85, Issue 2, Page(s) 110760

    Abstract: The SARS-CoV-2 pandemic has resulted in rapid research and vaccine development to help curtail unchecked transmission. However, these studies cannot be applied as easily among every population, such as immunocompromised individuals. In this study, we ... ...

    Abstract The SARS-CoV-2 pandemic has resulted in rapid research and vaccine development to help curtail unchecked transmission. However, these studies cannot be applied as easily among every population, such as immunocompromised individuals. In this study, we observed the humoral response of 70 total heart and renal transplant patients to mRNA SARS-CoV-2 vaccinations to help further understand the effectiveness of vaccination in post-transplant patients following second or booster vaccinations. Antibodies were measured by bead technology to detect IgG, as well as IgG/IgM Rapid Cassette tests for confirmation. Immunocompromised patients had a noticeably lower humoral response than non-immunocompromised populations, with an even lower response among Black patients. Our findings also show for the first time various antibody responses to different motifs of the virus, with the lowest being against the S2 motif. A potential link between the duration of immunosuppression and vaccine response was also observed, where patients on immunosuppressants for longer had a stronger response to vaccination compared to recent transplant patients in our study. In addition, younger transplant recipients had a better humoral response to vaccination, and vaccine effectiveness was disproportionate between races. This finding reinforces the continuation of the guidelines for accelerated vaccination schedules for immunocompromised patients.
    MeSH term(s) Humans ; COVID-19 Vaccines ; Transplant Recipients ; COVID-19 ; SARS-CoV-2 ; Immunocompromised Host ; Kidney Transplantation ; Immunoglobulin G ; Antibodies, Viral ; Vaccination
    Chemical Substances COVID-19 Vaccines ; Immunoglobulin G ; Antibodies, Viral
    Language English
    Publishing date 2024-02-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 801524-7
    ISSN 1879-1166 ; 0198-8859
    ISSN (online) 1879-1166
    ISSN 0198-8859
    DOI 10.1016/j.humimm.2024.110760
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Roles of HIV-1 Env variable regions in viral neutralization and vaccine development.

    Pinter, Abraham

    Current HIV research

    2007  Volume 5, Issue 6, Page(s) 542–553

    Abstract: A major focus of HIV-1 vaccine development has been directed towards a limited number of broadly conserved epitopes in the Envelope (Env) proteins that are sensitive neutralization targets in many primary isolates. However, evidence suggests that these ... ...

    Abstract A major focus of HIV-1 vaccine development has been directed towards a limited number of broadly conserved epitopes in the Envelope (Env) proteins that are sensitive neutralization targets in many primary isolates. However, evidence suggests that these epitopes are poorly immunogenic; similar antibodies are rarely produced by infected subjects, nor are they induced by various immunogens designed to express these epitopes. On the other hand, the major variable domains of Env are highly immunogenic; antibodies against these regions are common in sera of infected patients and easily generated upon immunization. Although these epitopes are extremely sensitive neutralization targets in some laboratory strains and primary isolates, the neutralization range of antibodies against these sites is limited. This review describes potent neutralization epitopes located in the variable regions of Env and discusses the bases for the limited neutralization breadth of antibodies against these targets. Strategies are discussed for using available information to design immunogens capable of exploiting the potential of these regions as vaccine targets.
    MeSH term(s) AIDS Vaccines/immunology ; Amino Acid Sequence ; Antigen-Antibody Reactions ; Epitope Mapping ; Epitopes/immunology ; HIV Envelope Protein gp120/chemistry ; HIV Envelope Protein gp120/immunology ; HIV Envelope Protein gp41/immunology ; HIV Infections/immunology ; HIV Infections/prevention & control ; HIV-1/immunology ; Humans ; Molecular Sequence Data ; Peptide Fragments/chemistry ; Peptide Fragments/immunology ; env Gene Products, Human Immunodeficiency Virus/immunology
    Chemical Substances AIDS Vaccines ; Epitopes ; HIV Envelope Protein gp120 ; HIV Envelope Protein gp41 ; HIV envelope protein gp120 (135-148) ; HIV envelope protein gp120 (305-321) ; Peptide Fragments ; env Gene Products, Human Immunodeficiency Virus
    Language English
    Publishing date 2007-11-26
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2192348-6
    ISSN 1873-4251 ; 1570-162X
    ISSN (online) 1873-4251
    ISSN 1570-162X
    DOI 10.2174/157016207782418470
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Brilacidin, a Non-Peptide Defensin-Mimetic Molecule, Inhibits SARS-CoV-2 Infection by Blocking Viral Entry.

    Xu, Chuan / Wang, Annie / Honnen, William / Pinter, Abraham / Weston, Warren K / Harness, Jane A / Narayanan, Aarthi / Chang, Theresa L

    EC microbiology

    2022  Volume 18, Issue 4, Page(s) 1–12

    Abstract: Brilacidin (PMX-30063), a non-peptide defensin-mimetic small molecule, inhibits SARS-CoV-2 viral infection but the anti-viral mechanism is not defined. Here we determined its effect on the specific step of the viral life cycle. Brilacidin blocked SARS- ... ...

    Abstract Brilacidin (PMX-30063), a non-peptide defensin-mimetic small molecule, inhibits SARS-CoV-2 viral infection but the anti-viral mechanism is not defined. Here we determined its effect on the specific step of the viral life cycle. Brilacidin blocked SARS-CoV-2 infection but had no effect after viral entry. Brilacidin inhibited pseudotyped SARS-CoV-2 viruses expressing spike proteins from the P.1 Brazil strain and the B.1.1.7 UK strain. Brilacidin affected viral attachment in hACE2-dependent and independent manners depending on the concentrations. The inhibitory effect on viral entry was not mediated through blocking the binding of either the spike receptor-binding domain or the spike S1 protein to hACE2 proteins. Taken together, brilacidin inhibits SARS-CoV-2 infection by blocking viral entry and is active against SARS-CoV-2 variants.
    Language English
    Publishing date 2022-03-08
    Publishing country Scotland
    Document type Journal Article
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Author Correction: Insights into next generation sequencing guided antibody selection strategies.

    Erasmus, M Frank / Ferrara, Fortunato / D'Angelo, Sara / Spector, Laura / Leal-Lopes, Camila / Teixeira, André A / Sørensen, Jesper / Nagpal, Suhani / Perea-Schmittle, Kathryn / Choudhary, Alok / Honnen, William / Calianese, David / Antonio Rodriguez Carnero, Luis / Cocklin, Simon / Greiff, Victor / Pinter, Abraham / Bradbury, Andrew R M

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 3090

    Language English
    Publishing date 2024-02-07
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-53751-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Correction: Performance of novel antibodies for lipoarabinomannan to develop diagnostic tests for Mycobacterium tuberculosis.

    Cantera, Jason L / Lillis, Lorraine M / Peck, Roger B / Moreau, Emmanuel / Schouten, James A / Davis, Paul / Zheng, Ruixiang B / Lowary, Todd L / Drain, Paul K / Andama, Alfred / Pinter, Abraham / Kawasaki, Masanori / Källenius, Gunilla / Sundling, Christopher / Dobos, Karen M / Flores, Danara / Chatterjee, Delphi / Murphy, Eileen / Halas, Olivia R /
    Boyle, David S

    PloS one

    2024  Volume 19, Issue 1, Page(s) e0297828

    Abstract: This corrects the article DOI: 10.1371/journal.pone.0274415.]. ...

    Abstract [This corrects the article DOI: 10.1371/journal.pone.0274415.].
    Language English
    Publishing date 2024-01-23
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0297828
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Human Defensins Inhibit SARS-CoV-2 Infection by Blocking Viral Entry

    Xu, Chuan / Wang, Annie / Marin, Mariana / Honnen, William / Ramasamy, Santhamani / Porter, Edith / Subbian, Selvakumar / Pinter, Abraham / Melikyan, Gregory B. / Lu, Wuyuan / Chang, Theresa L.

    Viruses. 2021 June 26, v. 13, no. 7

    2021  

    Abstract: Innate immunity during acute infection plays a critical role in the disease severity of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and is likely to contribute to COVID-19 disease outcomes. Defensins are highly ... ...

    Abstract Innate immunity during acute infection plays a critical role in the disease severity of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and is likely to contribute to COVID-19 disease outcomes. Defensins are highly abundant innate immune factors in neutrophils and epithelial cells, including intestinal Paneth cells, and exhibit antimicrobial and immune-modulatory activities. In this study, we investigated the effects of human α- and β-defensins and RC101, a θ-defensin analog, on SARS-CoV-2 infection. We found that human neutrophil peptides (HNPs) 1–3, human defensin (HD) 5 and RC101 exhibited potent antiviral activity against pseudotyped viruses expressing SARS-CoV-2 spike proteins. HNP4 and HD6 had weak anti-SARS-CoV-2 activity, whereas human β-defensins (HBD2, HBD5 and HBD6) had no effect. HNP1, HD5 and RC101 also inhibited infection by replication-competent SARS-CoV-2 viruses and SARS-CoV-2 variants. Pretreatment of cells with HNP1, HD5 or RC101 provided some protection against viral infection. These defensins did not have an effect when provided post-infection, indicating their effect was directed towards viral entry. Indeed, HNP1 inhibited viral fusion but not the binding of the spike receptor-binding domain to hACE2. The anti-SARS-CoV-2 effect of defensins was influenced by the structure of the peptides, as linear unstructured forms of HNP1 and HD5 lost their antiviral function. Pro-HD5, the precursor of HD5, did not block infection by SARS-CoV-2. High virus titers overcame the effect of low levels of HNP1, indicating that defensins act on the virion. HNP1, HD5 and RC101 also blocked viral infection of intestinal and lung epithelial cells. The protective effects of defensins reported here suggest that they may be useful additives to the antivirus arsenal and should be thoroughly studied.
    Keywords COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; antiviral properties ; epithelium ; humans ; innate immunity ; intestines ; lungs ; neutrophils ; peptides ; virion ; viruses
    Language English
    Dates of publication 2021-0626
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13071246
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Insights into next generation sequencing guided antibody selection strategies.

    Erasmus, M Frank / Ferrara, Fortunato / D'Angelo, Sara / Spector, Laura / Leal-Lopes, Camila / Teixeira, André A / Sørensen, Jesper / Nagpal, Suhani / Perea-Schmittle, Kathryn / Choudhary, Alok / Honnen, William / Calianese, David / Antonio Rodriguez Carnero, Luis / Cocklin, Simon / Greiff, Victor / Pinter, Abraham / Bradbury, Andrew R M

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 18370

    Abstract: Therapeutic antibody discovery often relies on in-vitro display methods to identify lead candidates. Assessing selected output diversity traditionally involves random colony picking and Sanger sequencing, which has limitations. Next-generation sequencing ...

    Abstract Therapeutic antibody discovery often relies on in-vitro display methods to identify lead candidates. Assessing selected output diversity traditionally involves random colony picking and Sanger sequencing, which has limitations. Next-generation sequencing (NGS) offers a cost-effective solution with increased read depth, allowing a comprehensive understanding of diversity. Our study establishes NGS guidelines for antibody drug discovery, demonstrating its advantages in expanding the number of unique HCDR3 clusters, broadening the number of high affinity antibodies, expanding the total number of antibodies recognizing different epitopes, and improving lead prioritization. Surprisingly, our investigation into the correlation between NGS-derived frequencies of CDRs and affinity revealed a lack of association, although this limitation could be moderately mitigated by leveraging NGS clustering, enrichment and/or relative abundance across different regions to enhance lead prioritization. This study highlights NGS benefits, offering insights, recommendations, and the most effective approach to leverage NGS in therapeutic antibody discovery.
    MeSH term(s) High-Throughput Nucleotide Sequencing/methods ; Antibodies/genetics ; Epitopes
    Chemical Substances Antibodies ; Epitopes
    Language English
    Publishing date 2023-10-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-45538-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Author Correction: Insights into next generation sequencing guided antibody selection strategies.

    Erasmus, M Frank / Ferrara, Fortunato / D'Angelo, Sara / Spector, Laura / Leal-Lopes, Camila / Teixeira, André A / Sørensen, Jesper / Nagpal, Suhani / Perea-Schmittle, Kathryn / Choudhary, Alok / Honnen, William / Calianese, David / Antonio Rodriguez Carnero, Luis / Cocklin, Simon / Greiff, Victor / Pinter, Abraham / Bradbury, Andrew R M

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 22616

    Language English
    Publishing date 2023-12-18
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-49214-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Predictors of chronic COVID-19 symptoms in a community-based cohort of adults.

    Silverberg, Jonathan I / Zyskind, Israel / Naiditch, Hiam / Zimmerman, Jason / Glatt, Aaron E / Pinter, Abraham / Theel, Elitza S / Joyner, Michael J / Hill, D Ashley / Lieberman, Miriam R / Bigajer, Elliot / Stok, Daniel / Frank, Elliot / Rosenberg, Avi Z

    PloS one

    2022  Volume 17, Issue 8, Page(s) e0271310

    Abstract: Background: COVID-19 can cause some individuals to experience chronic symptoms. Rates and predictors of chronic COVID-19 symptoms are not fully elucidated.: Objective: To examine occurrence and patterns of post-acute sequelae of SARS-CoV2 infection ( ... ...

    Abstract Background: COVID-19 can cause some individuals to experience chronic symptoms. Rates and predictors of chronic COVID-19 symptoms are not fully elucidated.
    Objective: To examine occurrence and patterns of post-acute sequelae of SARS-CoV2 infection (PASC) symptomatology and their relationship with demographics, acute COVID-19 symptoms and anti-SARS-CoV-2 IgG antibody responses.
    Methods: A multi-stage observational study was performed of adults (≥18 years) from 5 US states. Participants completed two rounds of electronic surveys (May-July 2020; April-May 2021) and underwent testing to anti-SARS-CoV-2 nucleocapsid protein IgG antibody testing. Latent Class Analysis was used to identify clusters of chronic COVID-19 symptoms.
    Results: Overall, 390 adults (median [25%ile, 75%ile] age: 42 [31, 54] years) with positive SARS-CoV-2 antibodies completed the follow-up survey; 92 (24.7%) had ≥1 chronic COVID-19 symptom, with 11-month median duration of persistent symptoms (range: 1-12 months). The most common chronic COVID-19 symptoms were fatigue (11.3%), change in smell (9.5%) or taste (5.6%), muscle or joint aches (5.4%) and weakness (4.6%). There were significantly higher proportions of ≥1 persistent COVID-19 symptom (31.5% vs. 18.6%; Chi-square, P = 0.004), and particularly fatigue (15.8% vs. 7.3%, P = 0.008) and headaches (5.4% vs. 1.0%, P = 0.011) in females compared to males. Chronic COVID-19 symptoms were also increased in individuals with ≥6 acute COVID-19 symptoms, Latent class analysis revealed 4 classes of symptoms. Latent class-1 (change of smell and taste) was associated with lower anti-SARS-CoV-2 antibody levels; class-2 and 3 (multiple chronic symptoms) were associated with higher anti-SARS-CoV-2 antibody levels and more severe acute COVID-19 infection.
    Limitations: Ambulatory cohort with less severe acute disease.
    Conclusion: Individuals with SARS-CoV-2 infection commonly experience chronic symptoms, most commonly fatigue, changes in smell or taste and muscle/joint aches. Female sex, severity of acute COVID-19 infection, and higher anti-SARS-CoV-2 IgG levels were associated with the highest risk of having chronic COVID-19 symptoms.
    MeSH term(s) Adult ; Antibodies, Viral ; COVID-19 ; Fatigue ; Female ; Humans ; Immunoglobulin G ; Male ; Pain ; RNA, Viral ; SARS-CoV-2
    Chemical Substances Antibodies, Viral ; Immunoglobulin G ; RNA, Viral
    Language English
    Publishing date 2022-08-04
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0271310
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Dichotomy between the humoral and cellular responses elicited by mRNA and adenoviral vector vaccines against SARS-CoV-2.

    Ukey, Rahul / Bruiners, Natalie / Mishra, Hridesh / Mishra, Pankaj K / McCloskey, Deborah / Onyuka, Alberta / Chen, Fei / Pinter, Abraham / Weiskopf, Daniela / Sette, Alessandro / Roy, Jason / Gaur, Sunanda / Gennaro, Maria Laura

    BMC medicine

    2022  Volume 20, Issue 1, Page(s) 32

    Abstract: Background: Protection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based ... ...

    Abstract Background: Protection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines.
    Main body: We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class 5 months earlier on average. After controlling for the time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in the mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between the two groups.
    Conclusions: A dichotomy exists between the humoral and cellular responses elicited by the two vaccine classes. Testing only for humoral responses to compare the durability of SARS-CoV-2 vaccine-induced responses, as typically performed for public health and research purposes, is insufficient.
    MeSH term(s) Ad26COVS1 ; Antibodies, Viral ; COVID-19 ; COVID-19 Vaccines ; Humans ; Immunity, Humoral ; RNA, Messenger/genetics ; SARS-CoV-2 ; Vaccination ; mRNA Vaccines
    Chemical Substances Ad26COVS1 ; Antibodies, Viral ; COVID-19 Vaccines ; RNA, Messenger ; mRNA Vaccines
    Language English
    Publishing date 2022-01-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2131669-7
    ISSN 1741-7015 ; 1741-7015
    ISSN (online) 1741-7015
    ISSN 1741-7015
    DOI 10.1186/s12916-022-02252-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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