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  1. Artikel ; Online: Severe dengue progression beyond enhancement.

    Odio, Camila D / Aogo, Rosemary A / Lowman, Kelsey E / Katzelnick, Leah C

    Nature immunology

    2023  Band 24, Heft 12, Seite(n) 1967–1969

    Mesh-Begriff(e) Humans ; Severe Dengue ; Dengue ; Dengue Virus ; Antibody-Dependent Enhancement ; Antibodies, Viral
    Chemische Substanzen Antibodies, Viral
    Sprache Englisch
    Erscheinungsdatum 2023-11-25
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-023-01680-1
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  2. Artikel ; Online: Spatial dynamics of inflammation-causing and commensal bacteria in the gastrointestinal tract.

    Aogo, Rosemary A / Tanaka, Mark M / Penington, Catherine J

    Journal of theoretical biology

    2022  Band 548, Seite(n) 111194

    Abstract: In recent years, new research programmes have been initiated to understand the role of gut bacteria in health and disease, enabled in large part by the emergence of high-throughput sequencing. As new genomic and other data emerge it will become important ...

    Abstract In recent years, new research programmes have been initiated to understand the role of gut bacteria in health and disease, enabled in large part by the emergence of high-throughput sequencing. As new genomic and other data emerge it will become important to explain observations in terms of underlying population mechanisms; for instance, it is of interest to understand how resident bacteria interact with their hosts and pathogens, and how they play a protective role. Connecting underlying processes with observed patterns is aided by the development of mathematical models. Here, we develop a spatial model of microbial populations in the gastrointestinal tract to explore conditions under which inflammation-causing bacteria can invade the gut and under which such pathogens become persistent. We find that pathogens invade both small and large intestine from even a relatively small inoculum size but are usually eliminated by the host response. When the immune response is weak, the pathogen is able to persist for a long period. Spatial structure affects these dynamics by creating moving refugia which facilitate bouts of pathogen resurgence and inflammation in persistent infections. Space also plays a role in repopulation by commensals after infection. We further find that the rate of decay of inflammation has a stronger effect on outcomes than the initiation of inflammation or other parameters. Finally, we explore the impact of partially inflammation-resistant commensals on these dynamics.
    Mesh-Begriff(e) Bacteria ; Gastrointestinal Tract ; Humans ; Immunity ; Inflammation ; Symbiosis
    Sprache Englisch
    Erscheinungsdatum 2022-06-20
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2972-5
    ISSN 1095-8541 ; 0022-5193
    ISSN (online) 1095-8541
    ISSN 0022-5193
    DOI 10.1016/j.jtbi.2022.111194
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  3. Artikel: High transmission of endemic human coronaviruses before and during the COVID-19 pandemic in adolescents in Cebu, Philippines.

    Joseph, Janet O / Ylade, Michelle / Daag, Jedas Veronica / Aogo, Rosemary / Crisostomo, Maria Vinna / Mpingabo, Patrick / Premkumar, Lakshmanane / Deen, Jacqueline / Katzelnick, Leah

    Research square

    2023  

    Abstract: Background: SARS-CoV-2, the causative agent of COVID-19, is a betacoronavirus belonging to the same genus as endemic human coronaviruses (hCoVs) OC43 and HKU1 and is distinct from alpha hCoVs 229E and NL63. In a study of adolescents in the Philippines, ... ...

    Abstract Background: SARS-CoV-2, the causative agent of COVID-19, is a betacoronavirus belonging to the same genus as endemic human coronaviruses (hCoVs) OC43 and HKU1 and is distinct from alpha hCoVs 229E and NL63. In a study of adolescents in the Philippines, we evaluated the seroprevalence to hCoVs, whether pre-pandemic hCoV immunity modulated subsequent risk of SARS-CoV-2 infection, and if SARS-CoV-2 infection affected the transmission of the hCoVs.
    Methods: From 499 samples collected in 2021 and screened by SARS-CoV-2 receptor binding domain (RBD) enzyme-linked immunosorbent assay (ELISA), we randomly selected 59 SARS-CoV-2 negative and 61 positive individuals for further serological evaluation. We measured RBD and spike antibodies to the four hCoVs and SARS-CoV-2 by ELISA in samples from the same participants collected pre-pandemic (2018-2019) and mid-pandemic (2021), before COVID-19 vaccination.
    Results: We observed over 72% seropositivity to the four hCoVs pre-pandemic. Binding antibodies increased with age to 229E and OC43, suggesting endemic circulation, while immunity was flat across ages for HKU1 and NL63. During the COVID-19 pandemic, antibody level increased significantly to the RBDs of OC43, NL63, and 229E and spikes of all four hCoVs in both SARS-CoV-2 negative and positive adolescents. Those aged 12-15 years old in 2021 had higher antibodies to RBD and spike of OC43, NL63, and 229E than adolescents the same age in 2019, further demonstrating intense transmission of the hCoVs during the pandemic.
    Conclusions: We observe a limited impact of the COVID-19 pandemic on endemic hCoV transmission. This study provides insight into co-circulation of hCoVs and SARS-CoV-2.
    Sprache Englisch
    Erscheinungsdatum 2023-11-16
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.21203/rs.3.rs-3581033/v1
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  4. Artikel ; Online: Effects of boosting and waning in highly exposed populations on dengue epidemic dynamics.

    Aogo, Rosemary A / Zambrana, Jose Victor / Sanchez, Nery / Ojeda, Sergio / Kuan, Guillermina / Balmaseda, Angel / Gordon, Aubree / Harris, Eva / Katzelnick, Leah C

    Science translational medicine

    2023  Band 15, Heft 722, Seite(n) eadi1734

    Abstract: Sequential infection with multiple dengue virus (DENV) serotypes is thought to induce enduring protection against dengue disease. However, long-term antibody waning has been observed after repeated DENV infection. Here, we provide evidence that highly ... ...

    Abstract Sequential infection with multiple dengue virus (DENV) serotypes is thought to induce enduring protection against dengue disease. However, long-term antibody waning has been observed after repeated DENV infection. Here, we provide evidence that highly immune Nicaraguan children and adults (
    Mesh-Begriff(e) Adult ; Child ; Humans ; Dengue/epidemiology ; Dengue Virus ; Antibodies, Viral ; Cross Reactions ; Zika Virus Infection ; Zika Virus
    Chemische Substanzen Antibodies, Viral
    Sprache Englisch
    Erscheinungsdatum 2023-11-15
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.adi1734
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  5. Artikel: Envelope-dimer epitope-like broadly protective antibodies against dengue in children following natural infection and vaccination.

    Mpingabo, Patrick I / Ylade, Michelle / Aogo, Rosemary A / Crisostomo, Maria Vinna / Thiono, Devina J / Daag, Jedas Veronica / Agrupis, Kristal-An / Escoto, Ana Coello / Raimundi-Rodriguez, Guillermo L / Odio, Camila D / Fernandez, Maria Abad / White, Laura / de Silva, Aravinda M / Deen, Jacqueline / Katzelnick, Leah C

    medRxiv : the preprint server for health sciences

    2024  

    Abstract: Cross-reactive antibodies (Abs) to epitopes that span envelope proteins on the virion surface are hypothesized to protect against dengue. Here, we measured Abs targeting the quaternary envelope dimer epitope (EDE) as well as neutralizing and binding Abs ... ...

    Abstract Cross-reactive antibodies (Abs) to epitopes that span envelope proteins on the virion surface are hypothesized to protect against dengue. Here, we measured Abs targeting the quaternary envelope dimer epitope (EDE) as well as neutralizing and binding Abs and evaluate their association with dengue virus (DENV) infection, vaccine response, and disease outcome in dengue vaccinated and unvaccinated children (n=252) within a longitudinal cohort in Cebu, Philippines (n=2,996). Abs targeting EDE were prevalent and strongly associated with broad neutralization of DENV1-4 in those with baseline multitypic immunity. Subsequent natural infection and vaccination boosted EDE-like, neutralizing, and binding Abs. EDE-like Abs were associated with reduced dengue risk and mediated the protective effect of binding and neutralizing Abs on symptomatic and severe dengue. Thus, Abs targeting quaternary epitopes help explain broad cross protection in those with multiple prior DENV exposures, making them useful for evaluation and development of future vaccines and therapeutics.
    Sprache Englisch
    Erscheinungsdatum 2024-05-01
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2024.04.30.24306574
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  6. Artikel: Dengue virus IgG and serotype-specific neutralizing antibody titers measured with standard and mature viruses are associated with protection.

    Katzelnick, Leah / Odio, Camila / Daag, Jedas / Crisostomo, Maria Vinna / Voirin, Charlie / Escoto, Ana Coello / Adams, Cameron / Hein, Lindsay Dahora / Aogo, Rosemary / Mpingabo, Patrick / Rodriguez, Guillermo Raimundi / Firdous, Saba / Fernandez, Maria Abad / White, Laura / Agrupis, Kristal-An / Deen, Jacqueline / de Silva, Aravinda / Ylade, Michelle

    Research square

    2024  

    Abstract: Recent work demonstrates the limitations of the standard dengue virus (DENV) neutralization assay to predict protection against dengue. We perform studies to compare how a commercial IgG ELISA, envelope domain III (EDIII) or non-structural protein 1 (NS1) ...

    Abstract Recent work demonstrates the limitations of the standard dengue virus (DENV) neutralization assay to predict protection against dengue. We perform studies to compare how a commercial IgG ELISA, envelope domain III (EDIII) or non-structural protein 1 (NS1) binding antibodies, and titers from plaque reduction neutralization tests (PRNTs) using reference standard and clinical mature viruses are associated with dengue disease. Healthy children (n = 1,206) in Cebu, Philippines were followed for 5 years. High ELISA values (≥3) were associated with reduced dengue probability relative to naïve children (3% vs. 10%, p = 0.008), but antibody binding EDIII or NS1 from each serotype had no association. High standard and mature geometric mean PRNT titers were associated with reduced dengue disease overall (p < 0.01), and high DENV2 and DENV3 titers in both assays provided protection against the matched serotype (p < 0.02). However, while 52% of dengue cases had standard virus PRNT titers > 100, only 2% of cases had mature virus PRNT titers > 100 (p < 0.001), indicating a lower, more consistent threshold for protection. Each assay may be useful for different purposes as correlates of protection in population and vaccine trials.
    Sprache Englisch
    Erscheinungsdatum 2024-04-12
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.21203/rs.3.rs-4145863/v1
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  7. Artikel: Leveraging Computational Modeling to Understand Infectious Diseases.

    Jenner, Adrianne L / Aogo, Rosemary A / Davis, Courtney L / Smith, Amber M / Craig, Morgan

    Current pathobiology reports

    2020  Band 8, Heft 4, Seite(n) 149–161

    Abstract: Purpose of review: Computational and mathematical modeling have become a critical part of understanding in-host infectious disease dynamics and predicting effective treatments. In this review, we discuss recent findings pertaining to the biological ... ...

    Abstract Purpose of review: Computational and mathematical modeling have become a critical part of understanding in-host infectious disease dynamics and predicting effective treatments. In this review, we discuss recent findings pertaining to the biological mechanisms underlying infectious diseases, including etiology, pathogenesis, and the cellular interactions with infectious agents. We present advances in modeling techniques that have led to fundamental disease discoveries and impacted clinical translation.
    Recent findings: Combining mechanistic models and machine learning algorithms has led to improvements in the treatment of
    Summary: Computational modeling is now more than ever at the forefront of infectious disease research due to the COVID-19 pandemic. This review highlights how infectious diseases can be better understood by connecting scientists from medicine and molecular biology with those in computer science and applied mathematics.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2020-09-24
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ISSN 2167-485X
    ISSN 2167-485X
    DOI 10.1007/s40139-020-00213-x
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  8. Artikel: Primary exposure to Zika virus increases risk of symptomatic dengue virus infection with serotypes 2, 3, and 4 but not serotype 1.

    Zambrana, Jose Victor / Hasund, Chloe M / Aogo, Rosemary A / Bos, Sandra / Arguello, Sonia / Gonzalez, Karla / Collado, Damaris / Miranda, Tatiana / Kuan, Guillermina / Gordon, Aubree / Balmaseda, Angel / Katzelnick, Leah / Harris, Eva

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: Infection with any of the four dengue virus serotypes (DENV1-4) can protect against or enhance subsequent dengue depending on pre-existing antibodies and the subsequent infecting serotype. Additionally, primary infection with the related flavivirus Zika ... ...

    Abstract Infection with any of the four dengue virus serotypes (DENV1-4) can protect against or enhance subsequent dengue depending on pre-existing antibodies and the subsequent infecting serotype. Additionally, primary infection with the related flavivirus Zika virus (ZIKV) has been shown to increase DENV2 disease. Here, we measured how prior DENV and ZIKV immunity influenced risk of disease caused by all four serotypes in a pediatric Nicaraguan cohort. Of 3,412 participants in 2022, 10.6% experienced symptomatic DENV infections caused by DENV1 (n=139), DENV4 (n=133), DENV3 (n=54), DENV2 (n=9), or an undetermined serotype (n=39). Longitudinal clinical and serological data were used to define infection histories, and generalized linear and additive models adjusted for age, sex, time since the last infection, cohort year, and repeat measurements were used to predict disease risk. Compared to flavivirus-naïve participants, primary ZIKV infection increased disease risk of DENV4 (relative risk = 2.62, 95% confidence interval: 1.48-4.63) and DENV3 (2.90, 1.34-6.27) but not DENV1 (1.20, 0.72-1.99). Primary DENV infection or a DENV followed by ZIKV infection also increased DENV4 risk. We re-analyzed 19 years of cohort data and demonstrated that prior flavivirus-immunity and pre-existing antibody titer differentially affected disease risk for incoming serotypes, increasing risk of DENV2 and DENV4, protecting against DENV1, and protecting at high titers but enhancing at low titers against DENV3. We thus find that prior ZIKV infection, like prior DENV infection, increases risk of certain DENV serotypes. Cross-reactivity among flaviviruses should be carefully considered when assessing vaccine safety and efficacy.
    Sprache Englisch
    Erscheinungsdatum 2023-11-30
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.11.29.23299187
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  9. Artikel ; Online: Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine.

    Odio, Camila D / Lowman, Kelsey E / Law, Melissa / Aogo, Rosemary A / Hunsberger, Sally / Wood, Brad J / Kassin, Michael / Levy, Elliot / Callier, Viviane / Firdous, Saba / Hasund, Chloe M / Voirin, Charlie / Kattappuram, Robbie / Yek, Christina / Manning, Jessica / Durbin, Anna / Whitehead, Stephen S / Katzelnick, Leah C

    BMC infectious diseases

    2023  Band 23, Heft 1, Seite(n) 345

    Abstract: Background: The four co-circulating and immunologically interactive dengue virus serotypes (DENV1-4) pose a unique challenge to vaccine design because sub-protective immunity can increase the risk of severe dengue disease. Existing dengue vaccines have ... ...

    Abstract Background: The four co-circulating and immunologically interactive dengue virus serotypes (DENV1-4) pose a unique challenge to vaccine design because sub-protective immunity can increase the risk of severe dengue disease. Existing dengue vaccines have lower efficacy in DENV seronegative individuals but higher efficacy in DENV exposed individuals. There is an urgent need to identify immunological measures that are strongly associated with protection against viral replication and disease following sequential exposure to distinct serotypes.
    Methods/design: This is a phase 1 trial wherein healthy adults with neutralizing antibodies to zero (seronegative), one non-DENV3 (heterotypic), or more than one (polytypic) DENV serotype will be vaccinated with the live attenuated DENV3 monovalent vaccine rDEN3Δ30/31-7164. We will examine how pre-vaccine host immunity influences the safety and immunogenicity of DENV3 vaccination in a non-endemic population. We hypothesize that the vaccine will be safe and well tolerated, and all groups will have a significant increase in the DENV1-4 neutralizing antibody geometric mean titer between days 0 and 28. Compared to the seronegative group, the polytypic group will have lower mean peak vaccine viremia, due to protection conferred by prior DENV exposure, while the heterotypic group will have higher mean peak viremia, due to mild enhancement. Secondary and exploratory endpoints include characterizing serological, innate, and adaptive cell responses; evaluating proviral or antiviral contributions of DENV-infected cells; and immunologically profiling the transcriptome, surface proteins, and B and T cell receptor sequences and affinities of single cells in both peripheral blood and draining lymph nodes sampled via serial image-guided fine needle aspiration.
    Discussion: This trial will compare the immune responses after primary, secondary, and tertiary DENV exposure in naturally infected humans living in non-endemic areas. By evaluating dengue vaccines in a new population and modeling the induction of cross-serotypic immunity, this work may inform vaccine evaluation and broaden potential target populations.
    Trial registration: NCT05691530 registered on January 20, 2023.
    Mesh-Begriff(e) Adult ; Humans ; Dengue Vaccines ; Viremia ; Vaccines, Attenuated ; Vaccination ; Antibodies, Neutralizing ; Severe Dengue
    Chemische Substanzen Dengue Vaccines ; Vaccines, Attenuated ; Antibodies, Neutralizing
    Sprache Englisch
    Erscheinungsdatum 2023-05-23
    Erscheinungsland England
    Dokumenttyp Clinical Trial, Phase I ; Journal Article
    ZDB-ID 2041550-3
    ISSN 1471-2334 ; 1471-2334
    ISSN (online) 1471-2334
    ISSN 1471-2334
    DOI 10.1186/s12879-023-08299-5
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  10. Artikel ; Online: Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice.

    SheelaNair, Arya / Romanczuk, Aleksandra S / Aogo, Rosemary A / Haldar, Rohit Nemai / Lansink, Lianne I M / Cromer, Deborah / Salinas, Yandira G / Guy, R Kiplin / McCarthy, James S / Davenport, Miles P / Haque, Ashraful / Khoury, David S

    Malaria journal

    2022  Band 21, Heft 1, Seite(n) 49

    Abstract: Background: Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized ... ...

    Abstract Background: Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the "parasite clearance curve", has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation.
    Methods: In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound's capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication.
    Results: These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal.
    Conclusions: Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites.
    Mesh-Begriff(e) Animals ; Antimalarials/pharmacology ; Antimalarials/therapeutic use ; Drug Combinations ; Heterocyclic Compounds, 4 or More Rings ; Isoquinolines ; Malaria/drug therapy ; Malaria/parasitology ; Mice ; Naphthyridines ; Parasites
    Chemische Substanzen Antimalarials ; Drug Combinations ; Heterocyclic Compounds, 4 or More Rings ; Isoquinolines ; Naphthyridines ; SJ733 ; pyronaridine (TD3P7Q3SG6)
    Sprache Englisch
    Erscheinungsdatum 2022-02-16
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2091229-8
    ISSN 1475-2875 ; 1475-2875
    ISSN (online) 1475-2875
    ISSN 1475-2875
    DOI 10.1186/s12936-022-04075-z
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