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  1. AU="Climent, Consuelo"
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  6. AU="Maria Camilla Cipriani"
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  34. AU=Meares Gordon P.
  35. AU="Gawron, Lori M"
  36. AU=Guettari Moez
  37. AU=Ma Xingcong
  38. AU="Greene, Kerrie" AU="Greene, Kerrie"
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  1. Artikel ; Online: Breast Cancer in a Caribbean Population in Transition: Design and Implementation of the Atabey Population-Based Case-Control Study of Women in the San Juan Metropolitan Area in Puerto Rico.

    Rosario-Rosado, Rosa V / Nazario, Cruz M / Hernández-Santiago, Johan / Schelske-Santos, Michelle / Mansilla-Rivera, Imar / Ramírez-Marrero, Farah A / Ramos-Valencia, Gilberto / Climent, Consuelo / Nie, Jing / Freudenheim, Jo L

    International journal of environmental research and public health

    2020  Band 17, Heft 4

    Abstract: Global breast cancer incidence varies considerably, particularly in comparisons of low- and high-income countries; rates may vary even within regions. Breast cancer rates for Caribbean countries are generally lower than for North America and Europe. ... ...

    Abstract Global breast cancer incidence varies considerably, particularly in comparisons of low- and high-income countries; rates may vary even within regions. Breast cancer rates for Caribbean countries are generally lower than for North America and Europe. Rates in Puerto Rico are in the middle of the range between the highest and the lowest Caribbean countries. Populations in transition, with greater variability in risk factor exposures, provide an important opportunity to better understand breast cancer etiology and as potential sources of variation in rates. Understanding of exposures across the life span can potentially contribute to understanding regional differences in rates. We describe here the design and implementation of a population-based, case-control study in the San Juan Metropolitan Area (SJMA) of Puerto Rico, the Atabey Epidemiology of Breast Cancer Study. We describe steps taken to ensure that the study was culturally appropriate, leveraging the Atabey researchers' understanding of the culture, local health system, and other required resources to effectively recruit participants. A standardized, in-person interview was developed, with attention to life course events customized to the study population. In order to understand variation in global breast cancer rates, studies customized to the populations outside of North America and Europe are required.
    Mesh-Begriff(e) Breast Neoplasms/epidemiology ; Case-Control Studies ; Female ; Humans ; Pregnancy ; Puerto Rico/epidemiology ; Risk Factors
    Sprache Englisch
    Erscheinungsdatum 2020-02-19
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1660-4601
    ISSN (online) 1660-4601
    DOI 10.3390/ijerph17041333
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination.

    Sariol, Carlos A A / Pantoja, Petraleigh / Serrano-Collazo, Crisanta / Rosa-Arocho, Tiffany / Armina-Rodríguez, Albersy / Cruz, Lorna / Stone, E Taylor Taylor / Arana, Teresa / Climent, Consuelo / Latoni, Gerardo / Atehortua, Dianne / Pabon-Carrero, Christina / Pinto, Amelia K K / Brien, James D D / Espino, Ana M M

    Viruses

    2021  Band 13, Heft 10

    Abstract: Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important ... ...

    Abstract Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients-despite a decline in total S-specific antibodies-neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. Our data suggest that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from ten out of the 59 subjects which received mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for the induction of a neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern observed after natural infection, the total anti-S antibodies titers declined after the second vaccine dose; however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. Furthermore, our data indicates that-compared with mRNA vaccination-natural infection induces a more robust humoral immune response in unexposed subjects. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies.
    Mesh-Begriff(e) Adult ; Aged ; Antibodies, Neutralizing/analysis ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; COVID-19/immunology ; COVID-19/physiopathology ; COVID-19 Vaccines/immunology ; Female ; Follow-Up Studies ; Humans ; Immunity, Humoral/genetics ; Immunity, Humoral/immunology ; Immunity, Humoral/physiology ; Male ; Middle Aged ; Protein Binding/genetics ; Protein Domains/genetics ; Puerto Rico/epidemiology ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/immunology ; Spike Glycoprotein, Coronavirus/physiology ; Vaccination
    Chemische Substanzen Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Sprache Englisch
    Erscheinungsdatum 2021-09-30
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13101972
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: Function is more reliable than quantity to follow up the humoral response to the Receptor Binding Domain of SARS- CoV-2 Spike protein after natural infection or COVID-19 vaccination.

    Sariol, Carlos A / Pantoja, Petraleigh / Serrano-Collazo, Crisanta / Rosa-Arocho, Tiffany / Armina, Albersy / Cruz, Lorna / Stone, E Taylor / Arana, Teresa / Climent, Consuelo / Latoni, Gerardo / Atehortua, Dianne / Pabon-Carrero, Christina / Pinto, Amelia K / Brien, James D / Espino, Ana M

    medRxiv : the preprint server for health sciences

    2021  

    Abstract: Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important ... ...

    Abstract Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients-despite a decline in total S-specific antibodies-neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. We also report that serum neutralization capacity correlates with IgG titers, wherein IgG1 was the predominant isotype (62.71%), followed by IgG4 (15.25%), IgG3 (13.56%), and IgG2 (8.47%) at the earliest tested timepoint. IgA titers were detectable in just 28.81% of subjects, and only 62.71% of subjects had detectable IgM in the first sample despite confirmation of infection by a molecular diagnostic assay. Our data suggests that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from 10 out of the 59 subjects which had received an initial first dose of mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for induction of neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern seen after natural infection, after the second vaccine dose, the total anti-S antibodies titers declined, however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. The decline in anti-S antibody titer, however, was significantly less in pre-exposed individuals, highlighting the potential for natural infection to prime a more robust immune response to the vaccine. Furthermore, our data indicates that-compared with mRNA vaccination-natural infection induces a more robust humoral immune response in unexposed subjects. However, this difference was significant only when neutralizing antibody titers were compared among the two groups. No differences were observed between naturally infected and vaccinated individuals when total anti-S antibodies and IgG titers were measured. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that a functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies. In this context, our results also support standardizing methods of assessing the humoral response to SARS-CoV-2 when determining vaccine efficacy and describing the immune correlates of protection for SARS-CoV-2.
    Sprache Englisch
    Erscheinungsdatum 2021-08-10
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2021.06.02.21257975
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: Expression of Basal-like Biomarkers in Triple Negative Invasive Breast Carcinoma in Puerto Rico.

    Agosto-Arroyo, Emmanuel / Climent, Consuelo / Vélez, Román / Nazario, Cruz M / Díaz, Mary V

    Puerto Rico health sciences journal

    2015  Band 34, Heft 2, Seite(n) 89–92

    Abstract: Objective: Routine Progesterone and Estrogen hormone receptor proteins and human epidermal growth factor receptor 2 (HER-2) analysis on invasive breast carcinomas provide therapeutic and prognostic values, revealing significant subgroups: luminal A, ... ...

    Abstract Objective: Routine Progesterone and Estrogen hormone receptor proteins and human epidermal growth factor receptor 2 (HER-2) analysis on invasive breast carcinomas provide therapeutic and prognostic values, revealing significant subgroups: luminal A, luminal B, HER-2 and the "triple negative" tumors. The aim of this study was to determine the expression of basal cytokeratins and Epidermal Growth Factor Receptor in "triple negative" invasive breast carcinomas in Puerto Rico women.
    Methods: All invasive breast carcinoma cases received from 2008 to 2010 were included. Assessment of tumoral expression of Estrogen Receptor, Progesterone Receptor and HER-2 was performed. The cases were divided into groups based on their molecular categories and analyzed according to the age. "Triple negative" tumors were further analyzed according to their expression of Epidermal Growth Factor Receptor and cytokeratins 5/6 and 14.
    Results: From 717 cases reviewed, 487 cases of invasive breast carcinoma were included. The molecular categories were 66%, 10%, 9% and 15% for the luminal A, luminal B, Her-2 and "triple negative" groups, respectively. No significant difference (p= 0.64) was observed between the molecular categories and the age of the patients. Assessment of basal cytokeratins and Epidermal Growth Factor Receptor expression was performed on 41 "triple negative" tumors; 71% expressed at least one basal cytokeratin or Epidermal Growth Factor Receptor and 29% were negative to all markers.
    Conclusion: Prevalence and relation between the molecular categories and the expression of basal cytokeratins in "triple negative" tumors in our population is comparable to other published data.
    Mesh-Begriff(e) Adult ; Aged ; Biomarkers, Tumor/biosynthesis ; ErbB Receptors/biosynthesis ; Female ; Humans ; Keratins/biosynthesis ; Middle Aged ; Neoplasm Invasiveness ; Puerto Rico ; Retrospective Studies ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/pathology
    Chemische Substanzen Biomarkers, Tumor ; Keratins (68238-35-7) ; ErbB Receptors (EC 2.7.10.1)
    Sprache Englisch
    Erscheinungsdatum 2015-06
    Erscheinungsland Puerto Rico
    Dokumenttyp Journal Article
    ZDB-ID 639137-0
    ISSN 0738-0658
    ISSN 0738-0658
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel: Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination

    Sariol, Carlos A. A. / Pantoja, Petraleigh / Serrano-Collazo, Crisanta / Rosa-Arocho, Tiffany / Armina-Rodríguez, Albersy / Cruz, Lorna / Stone, E. Taylor Taylor / Arana, Teresa / Climent, Consuelo / Latoni, Gerardo / Atehortua, Dianne / Pabon-Carrero, Christina / Pinto, Amelia K. K. / Brien, James D. D. / Espino, Ana M. M.

    Viruses. 2021 Sept. 30, v. 13, no. 10

    2021  

    Abstract: Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important ... ...

    Abstract Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients—despite a decline in total S-specific antibodies—neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. Our data suggest that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from ten out of the 59 subjects which received mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for the induction of a neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern observed after natural infection, the total anti-S antibodies titers declined after the second vaccine dose; however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. Furthermore, our data indicates that—compared with mRNA vaccination—natural infection induces a more robust humoral immune response in unexposed subjects. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies.
    Schlagwörter COVID-19 infection ; Latinos ; Severe acute respiratory syndrome coronavirus 2 ; antibody formation ; humoral immunity ; neutralization tests ; pandemic ; vaccination ; vaccines
    Sprache Englisch
    Erscheinungsverlauf 2021-0930
    Erscheinungsort Multidisciplinary Digital Publishing Institute
    Dokumenttyp Artikel
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13101972
    Datenquelle NAL Katalog (AGRICOLA)

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  6. Artikel: Comparison of outpatient point of care glucose testing vs venous glucose in the clinical laboratory.

    Velázquez Medina, Diana / Climent, Consuelo

    Puerto Rico health sciences journal

    2003  Band 22, Heft 4, Seite(n) 385–389

    Abstract: The purpose of this study was to evaluate the accuracy of glucometers in assessing glucose levels in outpatients. The investigation consisted in the analysis of retrospective validation data (obtained at the Clinical Laboratory of the Puerto Rico Medical ...

    Abstract The purpose of this study was to evaluate the accuracy of glucometers in assessing glucose levels in outpatients. The investigation consisted in the analysis of retrospective validation data (obtained at the Clinical Laboratory of the Puerto Rico Medical Services Administration) and the analysis of data obtained from forty outpatients. Glucose concentration was obtained from these outpatient samples using the patients' glucometers and a clinical laboratory analyzer (hexokinase method). Statistical analysis included descriptive and correlation measures and t-test. Results revealed that accurate glucose values were obtained by the glucometers utilized in both the validation process and the outpatients (POCT) procedure. The investigation also demonstrated the need by outpatients to receive proper training in handling their glucometers.
    Mesh-Begriff(e) Blood Chemical Analysis/instrumentation ; Blood Chemical Analysis/methods ; Blood Glucose/analysis ; Clinical Laboratory Techniques ; Humans ; Outpatients ; Point-of-Care Systems/standards ; Quality Control ; Reference Standards ; Reproducibility of Results
    Chemische Substanzen Blood Glucose
    Sprache Englisch
    Erscheinungsdatum 2003-12
    Erscheinungsland Puerto Rico
    Dokumenttyp Comparative Study ; Journal Article
    ZDB-ID 639137-0
    ISSN 0738-0658
    ISSN 0738-0658
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: H intragenic polymorphisms and haplotype analysis in the ornithine transcarbamylase (OTC) gene and their relevance for tracking the inheritance of OTC deficiency.

    Climent, Consuelo / Rubio, Vicente

    Human mutation

    2002  Band 20, Heft 5, Seite(n) 407–408

    Abstract: The "private" nature of most mutations causing ornithine transcarbamylase (OTC) deficiency makes mutation identification in the patients difficult. Further, the PCR-amplification technology generally used for the genetic diagnosis of the deficiency ... ...

    Abstract The "private" nature of most mutations causing ornithine transcarbamylase (OTC) deficiency makes mutation identification in the patients difficult. Further, the PCR-amplification technology generally used for the genetic diagnosis of the deficiency misses large deletions in carrier females. Intragenic OTC polymorphisms may allow detection of these deletions and may represent an alternative to mutation detection for prenatal diagnosis and carrier identification in families with a history of inherited OTC deficiency. A new highly informative polymorphism (allele frequencies, 0.66/0.34) in intron 3 of the OTC gene (IVS3-39_40insT) is reported here, and allelic frequencies of 16 additional intragenic OTC polymorphisms are determined in 133-35 (average per polymorphism, 72) unrelated chromosomes. In addition to the novel polymorphism, only three of the studied polymorphisms (Lys46Arg, allelic frequency 0.68/0.32; IVS3-8A>T, 0.34/0.66; Gln270Arg, 0.97/0.03) are confirmed to be informative. These provide, together with another reported polymorphism (IVS4-7A>G; reported allelic frequency 0.71/0.29; Plante and Tuchman, 1998), a set of highly valuable markers of the OTC gene. Nevertheless, the combined informativity of the studied polymorphisms is limited by their distribution in only four haplotypes with one of them predominating (65% of the sampled chromosomes). Although this haplotype composition may be restricted to the Iberian peninsula (the origin of the samples), more informative polymorphisms are required to increase the diagnostic potential and, particularly, to identify large deletions affecting OTC gene exons 5-10, where only one polymorphism of weak diagnostic value is known.
    Mesh-Begriff(e) Base Sequence ; Gene Frequency ; Haplotypes ; Humans ; Introns ; Molecular Sequence Data ; Ornithine Carbamoyltransferase/genetics ; Ornithine Carbamoyltransferase Deficiency Disease/diagnosis ; Ornithine Carbamoyltransferase Deficiency Disease/genetics ; Polymorphism, Genetic ; Sequence Analysis, DNA ; Sequence Deletion
    Chemische Substanzen Ornithine Carbamoyltransferase (EC 2.1.3.3)
    Sprache Englisch
    Erscheinungsdatum 2002-11
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1126646-6
    ISSN 1098-1004 ; 1059-7794
    ISSN (online) 1098-1004
    ISSN 1059-7794
    DOI 10.1002/humu.9076
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: Identification of seven novel missense mutations, two splice-site mutations, two microdeletions and a polymorphic amino acid substitution in the gene for ornithine transcarbamylase (OTC) in patients with OTC deficiency.

    Climent, Consuelo / Rubio, Vicente

    Human mutation

    2002  Band 19, Heft 2, Seite(n) 185–186

    Abstract: Ornithine transcarbamylase (OTC) deficiency, a X-linked disorder, is the most frequent inborn error of the urea cycle. Point mutations and small deletions/insertions in the OTC gene are responsible for the majority of the cases and have a "private" ... ...

    Abstract Ornithine transcarbamylase (OTC) deficiency, a X-linked disorder, is the most frequent inborn error of the urea cycle. Point mutations and small deletions/insertions in the OTC gene are responsible for the majority of the cases and have a "private" character with little recurrence. We report on eleven pathological changes in the OTC gene sequence detected in three males with mild clinical presentations, and in eight symptomatic females. All of these mutations are novel. Only one mutation affects a CpG mutational hot spot, whereas all but one of the mutations caused an abnormal SSCP of the corresponding PCR-amplified exon. Two mutations occurring in females involved one or two base deletions in codons 196 and 330, respectively, causing frameshift changes and premature termination. Another two mutations in a female and a male affected acceptor splice sites at bases -1 and -3 of the intron 6/exon 7 and intron 9/exon 10 junctions, respectively. All other mutations were point changes causing the simple amino acid substitutions (M1I, I160S, L191F, M206I, L301F, P305H and L341P), although the mutation M1I may abolish translation of the OTC polypeptide. This mutation coexisted in a female patient with the change T333A that appears to be a previously unreported polymorphism. The three male patients but only four of the eight female patients inherited the mutation.
    Mesh-Begriff(e) Adult ; Age of Onset ; Child ; Child, Preschool ; CpG Islands/genetics ; Exons/genetics ; Female ; Humans ; Infant ; Introns/genetics ; Male ; Mutation, Missense/genetics ; Ornithine Carbamoyltransferase/genetics ; Ornithine Carbamoyltransferase Deficiency Disease/enzymology ; Ornithine Carbamoyltransferase Deficiency Disease/genetics ; Polymorphism, Genetic/genetics ; Polymorphism, Single-Stranded Conformational ; RNA Splice Sites/genetics ; Sequence Deletion/genetics
    Chemische Substanzen RNA Splice Sites ; Ornithine Carbamoyltransferase (EC 2.1.3.3)
    Sprache Englisch
    Erscheinungsdatum 2002-02
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1126646-6
    ISSN 1098-1004 ; 1059-7794
    ISSN (online) 1098-1004
    ISSN 1059-7794
    DOI 10.1002/humu.9011
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: The receptor binding domain of SARS-CoV-2 spike is the key target of neutralizing antibody in human polyclonal sera

    Steffen, Tara L. / Stone, E. Taylor / Hassert, Mariah / Geerling, Elizabeth / Grimberg, Brian T. / Espino, Ana M. / Pantoja, Petraleigh / Climent, Consuelo / Hoft, Daniel F. / George, Sarah L. / Sariol, Carlos A. / Pinto, Amelia K. / Brien, James D.

    bioRxiv

    Abstract: Natural infection of SARS-CoV-2 in humans leads to the development of a strong neutralizing antibody response, however the immunodominant targets of the polyclonal neutralizing antibody response are still unknown. Here, we functionally define the role ... ...

    Abstract Natural infection of SARS-CoV-2 in humans leads to the development of a strong neutralizing antibody response, however the immunodominant targets of the polyclonal neutralizing antibody response are still unknown. Here, we functionally define the role SARS-CoV-2 spike plays as a target of the human neutralizing antibody response. In this study, we identify the spike protein subunits that contain antigenic determinants and examine the neutralization capacity of polyclonal sera from a cohort of patients that tested qRT-PCR-positive for SARS-CoV-2. Using an ELISA format, we assessed binding of human sera to spike subunit 1 (S1), spike subunit 2 (S2) and the receptor binding domain (RBD) of spike. To functionally identify the key target of neutralizing antibody, we depleted sera of subunit-specific antibodies to determine the contribution of these individual subunits to the antigen-specific neutralizing antibody response. We show that epitopes within RBD are the target of a majority of the neutralizing antibodies in the human polyclonal antibody response. These data provide critical information for vaccine development and development of sensitive and specific serological testing.
    Schlagwörter covid19
    Verlag BioRxiv; WHO
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2020.08.21.261727
    Datenquelle COVID19

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  10. Artikel ; Online: Function is more reliable than quantity to follow up the humoral response to the Receptor Binding Domain of SARS- CoV-2 Spike Protein after Natural Infection or COVID-19 vaccination

    Sariol, Carlos A / Pantoja, Petraleigh / Serrano-Collazo, Crisanta / Rosa-Arocho, Tiffant / Armina, Albersy / Cruz, Lorna / Stone, E. Taylor / Arana, Teresa / Climent, Consuelo / Latoni, Gerardo / Atheortua, Dianne / Pabon-Carrero, Christina / Pinto, Amelia K / Brien, James D / Espino, Ana M

    medRxiv

    Abstract: On this work we report that despite of a decline in the total anti-Spike antibodies the neutralizing antibodies remains at a similar level for an average of 98 days in a longitudinal cohort of 59 Hispanic/Latino exposed to SARS-CoV-2. We are also ... ...

    Abstract On this work we report that despite of a decline in the total anti-Spike antibodies the neutralizing antibodies remains at a similar level for an average of 98 days in a longitudinal cohort of 59 Hispanic/Latino exposed to SARS-CoV-2. We are also reporting that the percentage of neutralization correlates with the IgG titers and that in the first collected samples, IgG1 was the predominant isotype (62.71%), followed by IgG4 (15.25%), IgG3 (13.56%), and IgG2 (8.47%) during the tested period. The IgA was detectable in 28.81% of subjects. Only 62.71% of all subjects have detectable IgM in the first sample despite of confirmed infection by a molecular method. Our data suggests that 100% that seroconvert make detectable neutralizing antibody responses measured by a surrogate viral neutralization test. We also found that the IgG titers and neutralizing activity were higher after the first dose in 10 vaccinated subjects out of the 59 with prior infection compare to a subgroup of 21 subjects naive to SARS-CoV-2. One dose was enough but two were necessary to reach the maximum percentage of neutralization in subjects with previous natural infection or naive to SARS-CoV-2 respectively. Like the pattern seen after the natural infection, after the second vaccine dose, the total anti-S antibodies and titers declined but not the neutralizing activity which remains at same levels for more than 80 days after the first vaccine dose. That decline, however, was significantly lower in pre-exposed individuals which denotes the contribution of the natural infection priming a more robust immune response to the vaccine. Also, our data indicates that the natural infection induces a more robust humoral immune response than the first vaccine dose in unexposed subjects. However, the difference was significant only when the neutralization was measured but not by assessing the total anti-S antibodies or the IgG titers. This work is an important contribution to understand the natural immune response to the novel coronavirus in a population severely hit by the virus. Also provide an invaluable data by comparing the dynamic of the immune response after the natural infection vs. the vaccination and suggesting that a functional test is a better marker than the presence or not of antibodies. On this context our results are also highly relevant to consider standardizing methods that in addition to serve as a tool to follow up the immune response to the vaccines may also provide a correlate of protection.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2021-06-03
    Verlag Cold Spring Harbor Laboratory Press
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2021.06.02.21257975
    Datenquelle COVID19

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