19 results on '"Rebeca Santano"'
Search Results
2. Immunogenicity and crossreactivity of antibodies to the nucleocapsid protein of SARS-CoV-2: utility and limitations in seroprevalence and immunity studies
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Rubén López-Aladid, Luis Izquierdo, Francisco Carmona-Torre, Gemma Moncunill, Ruth Aguilar, Antoni Torres, Carlo Carolis, Natalia Rodrigo Melero, Matija Popovic, Alberto L. García-Basteiro, Alfredo Mayor, Jordi Chi, Laia Fernández-Barat, Marta Vidal, Carlota Dobaño, Alfons Jiménez, Marta Tortajada, Gabriel Reina, and Rebeca Santano
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Male ,0301 basic medicine ,MFI, median fluorescence intensity ,Rhinovirus ,viruses ,LOESS, locally estimated scatterplot smoothing ,Antibodies, Viral ,medicine.disease_cause ,0302 clinical medicine ,Seroepidemiologic Studies ,FL, full-length ,skin and connective tissue diseases ,COVID-19, coronavirus disease 2019 ,biology ,Immunogenicity ,RBD, receptor-binding domain ,virus diseases ,Common cold ,General Medicine ,CT, C-terminus ,030220 oncology & carcinogenesis ,ADE, antibody-dependent disease enhancement ,Female ,Antibody ,S, spike ,Alpha (ethology) ,Cross Reactions ,SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 ,Article ,rRT-PCR, real-time reverse-transcriptase polymerase chain reaction ,NT, N-terminus ,03 medical and health sciences ,Immunity ,Physiology (medical) ,medicine ,Coronavirus Nucleocapsid Proteins ,Humans ,Seroprevalence ,Biochemistry, medical ,SARS-CoV-2 ,M, month ,fungi ,Biochemistry (medical) ,Public Health, Environmental and Occupational Health ,COVID-19 ,HCoV, common cold human coronavirus ,medicine.disease ,Virology ,body regions ,030104 developmental biology ,Immunoglobulin G ,biology.protein ,N, nucleocapsid - Abstract
COVID-19 patients elicit strong responses to the nucleocapsid (N) protein of SARS-CoV-2 but binding antibodies are also detected in prepandemic individuals, indicating potential crossreactivity with common cold human coronaviruses (HCoV) and questioning its utility in seroprevalence studies. We investigated the immunogenicity of the full-length and shorter fragments of the SARS-CoV-2 N protein, and the crossreactivity of antibodies with HCoV. We identified a C-terminus region in SARS-CoV2 N of minimal sequence homology with HCoV that was more specific for SARS-CoV-2 and highly immunogenic. IgGs to the full-length SARS-CoV-2 N also recognized N229E N, and IgGs to HKU1 N recognized SARS-CoV-2 N. Crossreactivity with SARS-CoV-2 was stronger for alpha- rather than beta-HCoV despite having less sequence identity, revealing the importance of conformational recognition. Higher preexisting IgG to OC43 N correlated with lower IgG to SARS-CoV-2 N in rRT-PCR negative individuals, reflecting less exposure and indicating a potential protective association. Antibodies to SARS-CoV-2 N were higher in patients with more severe and longer duration of symptoms and in females. IgGs remained stable for at least 3 months, while IgAs and IgMs declined faster. In conclusion, N protein is a primary target of SARS-CoV-2-specific and HCoV crossreactive antibodies, both of which may affect the acquisition of immunity to COVID-19.
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- 2021
3. SARS-CoV-2 Seroprevalence and Antibody Kinetics Among Health Care Workers in a Spanish Hospital After 3 Months of Follow-up
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Patricia Sotomayor, Neus Rosell, Antoni Trilla, Alfons Jiménez, Sarah R. Williams, M. Martinez, Angeline Cruz, Gemma Moncunill, Rebeca Santano, Robert A. Mitchell, Pilar Varela, Sergi Sanz, Diana Barrios, Selena Alonso, Montserrat Lamoglia, Javier Rodríguez Moreno, Anna Vilella, Marta Vidal, Alfredo Mayor, Alberto L. García-Basteiro, Laura Puyol, Jochen Hecht, Sara Torres, Nuria Pey, Carlo Carolis, Eugenia Chóliz, Marta Ribes, Susana Méndez, Carlota Dobaño, Antía Figueroa-Romero, Natalia Ortega, Pau Cisteró, Anna Llupià, Silvia Fochs, Sonia Barroso, Chenjerai Jairoce, Marta Tortajada, and Ruth Aguilar
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Adult ,Male ,0301 basic medicine ,Immunoglobulin A ,medicine.medical_specialty ,Health Personnel ,Antibodies, Viral ,health care workers ,Immunoglobulin G ,Subclass ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Seroepidemiologic Studies ,Internal medicine ,Major Article ,medicine ,Humans ,antibodies ,Immunology and Allergy ,Seroprevalence ,030212 general & internal medicine ,seroprevalence ,biology ,SARS-CoV-2 ,business.industry ,longitudinal cohort ,COVID-19 ,Middle Aged ,Kinetics ,Cross-Sectional Studies ,AcademicSubjects/MED00290 ,030104 developmental biology ,Infectious Diseases ,Immunoglobulin M ,Seroconversion ,Spain ,Cohort ,biology.protein ,Female ,Antibody ,business ,Follow-Up Studies - Abstract
Background At the COVID-19 spring 2020 pandemic peak in Spain, prevalence of SARS-CoV-2 infection in a cohort of 578 randomly selected health care workers (HCWs) from Hospital Clínic de Barcelona was 11.2%. Methods A follow-up survey 1 month later (April-May 2020) measured infection by rRT-PCR and IgM, IgA, and IgG to the receptor-binding domain of the spike protein by Luminex. Antibody kinetics, including IgG subclasses, was assessed until month 3. Results At month 1, the prevalence of infection measured by rRT-PCR and serology was 14.9% (84/565) and seroprevalence 14.5% (82/565). We found 25 (5%) new infections in 501 participants without previous evidence of infection. IgM, IgG, and IgA levels declined in 3 months (antibody decay rates 0.15 [95% CI, .11–.19], 0.66 [95% CI, .54–.82], and 0.12 [95% CI, .09–.16], respectively), and 68.33% of HCWs had seroreverted for IgM, 3.08% for IgG, and 24.29% for IgA. The most frequent subclass responses were IgG1 (highest levels) and IgG2, followed by IgG3, and only IgA1 but no IgA2 was detected. Conclusions Continuous and improved surveillance of SARS-CoV-2 infections in HCWs remains critical, particularly in high-risk groups. The observed fast decay of IgA and IgM levels has implications for seroprevalence studies using these isotypes., SARS-CoV-2 prevalence in 578 health care workers increased from 11.2% at the COVID-19 pandemic peak to 14.9% 1 month later. IgM, IgG, and IgA levels declined over 3 months of follow-up with 68.33%, 3.08%, and 24.29% of seroreversions, respectively.
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- 2020
4. Evaluation of antibody serology to determine current helminth and Plasmodium falciparum infections in a co-endemic area in Southern Mozambique
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Rebeca Santano, Rocío Rubio, Berta Grau-Pujol, Valdemiro Escola, Osvaldo Muchisse, Inocência Cuamba, Marta Vidal, Gemma Ruiz-Olalla, Ruth Aguilar, Javier Gandasegui, Maria Demontis, Jose Carlos Jamine, Anélsio Cossa, Charfudin Sacoor, Jorge Cano, Luis Izquierdo, Chetan E. Chitnis, Ross L Coppel, Virander Chauhan, David Cavanagh, Sheetij Dutta, Evelina Angov, Lisette van Lieshout, Bin Zhan, José Muñoz, Carlota Dobaño, and Gemma Moncunill
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parasitic diseases - Abstract
BackgroundSoil-transmitted helminths (STH), Schistosoma spp. and Plasmodium falciparum are parasites of major public health importance and co-endemic in many sub-Saharan African countries. Management of these infections requires detection and treatment of infected people and evaluation of large-scale measures implemented. Diagnostic tools are available but their low sensitivity, especially for low intensity helminth infections, leaves room for improvement. Antibody serology could be a useful approach thanks to its potential to detect both current infection and past exposure.MethodologyWe evaluated total IgE responses and specific-IgG levels to 9 antigens from STH, 2 from Schistosoma spp., and 16 from P. falciparum, as potential markers of current infection in a population of children and adults from Southern Mozambique (N = 715). Antibody responses were measured by quantitative suspension array Luminex technology and their performance was evaluated by ROC curve analysis using microscopic and molecular detection of infections as reference.Principal findingsIgG against the combination of EXP1, AMA1 and MSP2 (P. falciparum) in children and NIE (Strongyloides stercoralis) in adults and children had the highest accuracies (AUC = 0.942 and AUC = 0.872, respectively) as markers of current infection. IgG against the combination of MEA and Sm25 (Schistosoma spp.) were also reliable markers of current infection (AUC = 0.779). In addition, IgG seropositivity against 20 out of the 27 antigens in the panel differentiated the seropositive endemic population from the non-endemic population, suggesting a possible role as markers of exposure.ConclusionsWe provided evidence for the utility of antibody serology to detect current infection with parasites causing tropical diseases in endemic populations. In addition, most of the markers could be used as markers of exposure. We also showed the feasibility of measuring antibody serology with a platform that allows the integration of control and elimination programs for different pathogens.AUTHOR SUMMARYParasitic worms and Plasmodium falciparum, the causal agent of malaria, are among the most relevant parasitic diseases of our time and efforts are under way for their control and, ultimately, elimination. An accurate diagnosis is relevant for case management, but also allows calculating the prevalence and evaluating the effectiveness of treatment and control measures. Unfortunately, current diagnostic methods for parasitic worms are not optimal and many infections remain undetected. As for P. falciparum, current diagnostic techniques are satisfactory but do not allow for ascertaining exposure, which is relevant for evaluating control measures. Here we investigated the utility of measuring antibodies to these parasites as a diagnostic method. Our results indicate that it is possible to detect current infection with parasitic worms and P. falciparum using antibody detection with a moderate to high accuracy. We also show that antibodies could distinguish a population from Southern Mozambique, where these infections are prevalent, from a Spanish population never exposed to those parasites. Importantly, we used a platform that allows for the simultaneous detection of immunoglobulins to different parasites, which would be extremely useful as a tool to integrate control and elimination programs for several pathogens.
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- 2022
5. Antibody conversion rates to SARS-CoV-2 in saliva from children attending summer schools in Barcelona, Spain
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Laura Puyol, Gemma Pons Tomas, Marta Vidal, Rebeca Santano, Gemma Moncunill, Gemma Ruiz-Olalla, Luis Izquierdo, Iolanda Jordan, María Melé Casas, Robert A. Mitchell, Quique Bassat, Ruth Aguilar, Cristina Jou, Diana Barrios, Leonie Mayer, María Hernández García, Eduard Gratacós, Monica Girona-Alarcon, Jordi Chi, Claudia Fortuny, Selena Alonso, Rocío Rubio, Natalia Rodrigo Melero, Marta Cubells, Juan José García-García, Carmen Muñoz-Almagro, Mariona Fernández de Sevilla, Chenjerai Jairoce, Alfons Jiménez, Elisenda Bonet-Carne, Carlota Dobaño, Aleix Garcia-Miquel, Joana Claverol, Carlo Carolis, and Victoria Fumadó
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Saliva ,Antígens ,Antibodies, Viral ,COVID-19 (Malaltia) ,Pandemic ,Schools ,Child ,Children ,Conversión de anticuerpos ,biology ,Entorn escolar ,General Medicine ,SARS-CoV-2 ,Child, Preschool ,Spike Glycoprotein, Coronavirus ,Medicine ,Female ,Antibody ,medicine.symptom ,Escuelas ,Infants ,Viral load ,Research Article ,Adult ,616.9 ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Conversió d'anticossos ,Asymptomatic ,Nens ,Antigen ,medicine ,Humans ,Antigens ,Pandemics ,Niños ,business.industry ,Antibody conversion ,COVID-19 ,Escoles ,School environment ,Spain ,Immunoglobulin G ,Immunology ,biology.protein ,business - Abstract
Background: Surveillance tools to estimate viral transmission dynamics in young populations are essential to guide recommendations for school opening and management during viral epidemics. Ideally, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We aimed to estimate SARS-CoV-2 infection rates in children and adult populations in a school-like environment during the initial COVID-19 pandemic waves using an antibody-based field-deployable and non-invasive approach. Methods: Saliva antibody conversion defined as ≥ 4-fold increase in IgM, IgA, and/or IgG levels to five SARS-CoV-2 antigens including spike and nucleocapsid constructs was evaluated in 1509 children and 396 adults by high-throughput Luminex assays in samples collected weekly in 22 summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29th to July 31st, 2020. Results: Saliva antibody conversion between two visits over a 5-week period was 3.22% (49/1518) or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) assessed by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19. Conclusion: Saliva antibody profiling including three isotypes and multiplexing antigens is a useful and user-friendlier tool for screening pediatric populations to detect low viral load exposures among children, particularly while they are not vaccinated and vulnerable to highly contagious variants, and to recommend public health policies during pandemics. This work was supported by the Departament de Salut, Generalitat de Catalunya (grant number SLT006/17/00109). L.I. work was supported by PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400008C). ISGlobal receives support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program
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- 2021
6. Publisher Correction: Agreement between commercially available ELISA and in-house Luminex SARS-CoV-2 antibody immunoassays
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Eduard Gratacós, Gemma Moncunill, Rebeca Santano, Jordi Chi, Francesca Crovetto, Fatima Crispi, Carlota Dobaño, Diana Barrios, Marta Vidal, and Luis Izquierdo
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2019-20 coronavirus outbreak ,Multidisciplinary ,biology ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Virology ,biology.protein ,Medicine ,Antibody ,business - Published
- 2021
7. Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses
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Selena Alonso, Luis Izquierdo, Robert A. Mitchell, Benjamin Trinité, Alfons Jiménez, Pablo Engel, Pau Serra, Pablo Hernández-Luis, Laura Puyol, Pere Santamaria, Rebeca Santano, Natalia Rodrigo Melero, Carlota Dobaño, Montserrat Lamoglia, Natalia Ortega, Neus Rosell, Daniel Parras, Julià Blanco, Edwards Pradenas, Marta Ribes, Antoni Trilla, Angeline Cruz, Diana Barrios, Sarah R. Williams, Carlo Carolis, Marta Vidal, Rocío Rubio, Susana Méndez, Sonia Barroso, Pilar Varela, Alfredo Mayor, Ana Angulo, Ruth Aguilar, Gemma Moncunill, Chenjerai Jairoce, Marta Tortajada, Alberto L. García-Basteiro, Jordi Chi, Anna Vilella, and Anna Llupià
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Cross Protection ,viruses ,Science ,Common Cold ,General Physics and Astronomy ,Antibodies, Viral ,Asymptomatic ,Article ,General Biochemistry, Genetics and Molecular Biology ,Neutralization ,Immune system ,Antigen ,Coronavirus 229E, Human ,Immunity ,medicine ,Humans ,Seroprevalence ,Antigens, Viral ,Multidisciplinary ,biology ,SARS-CoV-2 ,business.industry ,COVID-19 ,virus diseases ,Common cold ,General Chemistry ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Antibodies, Neutralizing ,Immunoglobulin A ,Coronavirus NL63, Human ,Immunoglobulin M ,Viral infection ,Immunoglobulin G ,Immunology ,biology.protein ,medicine.symptom ,Antibody ,Infection ,business - Abstract
Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months (N = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease., Long-term characterisation of SARS-CoV-2 antibody kinetics is needed to understand the protective role of the immune response. Here the authors describe antibody levels and neutralisation activity in healthcare workers over seven months and investigate the role of immunity to endemic human coronaviruses.
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- 2021
8. Plasmodium falciparumand helminth coinfections increase IgE and parasite-specific IgG responses
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Rebeca Santano, Evelina Angov, Ross L. Coppel, Chauhan, Bin Zhan, Escola, Demontis M, Jose Muñoz, Jorge Cano, Pau Cisteró, Chetan E. Chitnis, Inocencia Cuamba, van Lieshout L, Gemma Ruiz-Olalla, Deepak Gaur, Gemma Moncunill, Anelsio Cossa, David R. Cavanagh, Ruth Aguilar, Carlota Dobaño, Jose Carlos Jamine, Berta Grau-Pujol, Rocío Rubio, Charfudin Sacoor, Marta Vidal, Muchisse O, Sheetij Dutta, and Luis Izquierdo
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biology ,Plasmodium falciparum ,Parasitemia ,Immunoglobulin E ,medicine.disease ,biology.organism_classification ,Serology ,Antigen ,parasitic diseases ,Immunology ,biology.protein ,medicine ,Coinfection ,Helminths ,Ascaris lumbricoides - Abstract
Coinfection withPlasmodium falciparumand helminths may impact the immune response to these parasites since they induce different immune profiles. We studied the effects of coinfections on the antibody profile in a cohort of 715 Mozambican children and adults using the Luminex technology with a panel of 16 antigens fromP. falciparumand 11 antigens from helminths (Ascaris lumbricoides, hookworm,Trichuris trichiura,Strongyloides stercoralisandSchistosomaspp.) and measured antigen-specific IgG and total IgE responses. We compared the antibody profile between groups defined byP. falciparumand helminth previous exposure (based on serology) and/or current infection (determined by microscopy and/or qPCR). In multivariable regression models adjusted by demographic, socioeconomic, water and sanitation variables, individuals exposed/infected withP. falciparumand helminths had significantly higher total IgE and antigen-specific IgG levels, magnitude (sum of all levels) and breadth of response to both types of parasites compared to individuals exposed/infected with only one type of parasite (p≤ 0.05). There was a positive association between exposure/infection toP. falciparumand exposure/infection to helminths or the number of helminth species, andvice versa(p≤ 0.001). In addition, children coexposed/coinfected tended (p= 0.062) to have higherP. falciparumparasitemia than those single exposed/infected. Our results suggest that an increase in the antibody responses in coexposed/coinfected individuals may reflect higher exposure and be due to a more permissive immune environment to infection in the host.GRAPHICAL ABSTRACT
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- 2021
9. SARS-CoV-2 seroprevalence and characteristics of post-infection immunity in a general population cohort study in Catalonia, Spain
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Serena Fossati, Manolis Kogevinas, Gemma Moncunill, Rebeca Santano, Leonie Mayer, Gemma Castaño-Vinyals, Martine Vrijheid, Diana Barrios, Marta Vidal, Vanessa Pleguezuelos, Rafael de Cid, Marianna Karachaliou, Beatriz Cortés, Rocío Rubio, Anna Carreras, Laura Puyol, Ioar Rivas, Carlota Dobaño, Alfons Jiménez, Cristina O'Callaghan-Gordo, Luis Izquierdo, Delphine Casabonne, Judith Garcia-Aymerich, Xavier Basagaña, Ruth Aguilar, and Ana Espinosa
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business.industry ,Immunity ,Environmental health ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,General Population Cohort ,Medicine ,Seroprevalence ,business ,Post infection - Abstract
Sparse data exist on the complex natural immunity to SARS-CoV-2 at the population level. We applied a well-validated multiplex serology test in 5000 participants of a general population study in Catalonia in blood samples collected from end June to mid November 2020. Based on responses to fifteen isotype-antigen combinations, we detected a seroprevalence of 18.1% in adults (n=4740), and modeled extrapolation to the general population of Catalonia indicated a 15.3% seroprevalence. Antibodies persistedup to 9 months after infection. Immune profiling of infected individuals revealed that with increasing severity of infection (asymptomatic, 1-3 symptoms, ≥4 symptoms, admitted to hospital/ICU), seroresponses were more robust and rich with a shift towardsIgG over IgA and anti-spike over anti-nucleocapsid responses. Among seropositive participants, lower antibody levels were observed for those ≥60 years vs
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- 2021
10. Antibody Conversion rates to SARS-CoV-2 in Saliva from Children Attending Summer Schools in Barcelona, Spain
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Laura Puyol, Claudia Fortuny, Rebeca Santano, Carlo Carolis, Monica Girona-Alarcon, Joana Claverol, Luis Izquierdo, Alonso Selena, Elisenda Bonet-Carne, Iolanda Jordan, Victoria Fumadó, Ruth Aguilar, Chenjerai Jairoce, Jordi Chi, Aleix Garcia-Miquel, Marta Cubells, Leonie Mayer, María Hernández García, Carmen Muñoz-Almagro, Natalia Rodrigo Melero, Marta Vidal, Juan José García-García, Eduard Gratacós, Mariona Fernández de Sevilla, Gemma Ruiz-Olalla, Rocío Rubio, Cristina Jou, Diana Barrios, Gemma Pons Tomas, Robert A. Mitchell, Alfons Jiménez, María Melé Casas, Gemma Moncunill, Carlota Dobaño, and Quique Bassat
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Saliva ,biology ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Asymptomatic ,Antigen ,Pandemic ,Immunology ,biology.protein ,medicine ,Antibody ,medicine.symptom ,business ,Viral load - Abstract
Surveillance tools to estimate infection rates in young populations are essential to guide recommendations for school reopening and management during viral epidemics. Ideally, field-deployable non-invasive, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We determined SARS-CoV-2 antibody conversion by high-throughput Luminex assays in saliva samples collected weekly in 1,509 children and 396 adults in 22 Summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29thto July 31st2020, between the first and second COVID-19 pandemic waves. Saliva antibody conversion defined as ≥4-fold increase in IgM, IgA and/or IgG levels to SARS-CoV-2 antigens between two visits over a 5-week period was 3.22% (49/1518), or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19. To conclude, saliva antibody profiling including three isotypes and multiplexing antigens is a useful and more user-friendly tool for screening pediatric populations to determine SARS-CoV-2 exposure and guide public health policies during pandemics.
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- 2021
11. Evaluation of antibody serology to determine current helminth and Plasmodium falciparum infections in a co-endemic area in Southern Mozambique
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Rebeca Santano, Rocío Rubio, Berta Grau-Pujol, Valdemiro Escola, Osvaldo Muchisse, Inocência Cuamba, Marta Vidal, Gemma Ruiz-Olalla, Ruth Aguilar, Javier Gandasegui, Maria Demontis, Jose Carlos Jamine, Anélsio Cossa, Charfudin Sacoor, Jorge Cano, Luis Izquierdo, Chetan E. Chitnis, Ross L. Coppel, Virander Chauhan, David Cavanagh, Sheetij Dutta, Evelina Angov, Lisette van Lieshout, Bin Zhan, José Muñoz, Carlota Dobaño, Gemma Moncunill, and Mahanty, Siddhartha
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Adult ,Infectious Diseases ,Helminths ,Immunoglobulin G ,Plasmodium falciparum ,Public Health, Environmental and Occupational Health ,Animals ,Humans ,Schistosoma ,Malaria, Falciparum ,Child ,Mozambique - Abstract
Background Soil-transmitted helminths (STH), Schistosoma spp. and Plasmodium falciparum are parasites of major public health importance and co-endemic in many sub-Saharan African countries. Management of these infections requires detection and treatment of infected people and evaluation of large-scale measures implemented. Diagnostic tools are available but their low sensitivity, especially for low intensity helminth infections, leaves room for improvement. Antibody serology could be a useful approach thanks to its potential to detect both current infection and past exposure. Methodology We evaluated total IgE responses and specific-IgG levels to 9 antigens from STH, 2 from Schistosoma spp., and 16 from P. falciparum, as potential markers of current infection in a population of children and adults from Southern Mozambique (N = 715). Antibody responses were measured by quantitative suspension array Luminex technology and their performance was evaluated by ROC curve analysis using microscopic and molecular detection of infections as reference. Principal findings IgG against the combination of EXP1, AMA1 and MSP2 (P. falciparum) in children and NIE (Strongyloides stercoralis) in adults and children had the highest accuracies (AUC = 0.942 and AUC = 0.872, respectively) as markers of current infection. IgG against the combination of MEA and Sm25 (Schistosoma spp.) were also reliable markers of current infection (AUC = 0.779). In addition, IgG seropositivity against 20 out of the 27 antigens in the panel differentiated the seropositive endemic population from the non-endemic population, suggesting a possible role as markers of exposure although sensitivity could not be assessed. Conclusions We provided evidence for the utility of antibody serology to detect current infection with parasites causing tropical diseases in endemic populations. In addition, most of the markers have potential good specificity as markers of exposure. We also showed the feasibility of measuring antibody serology with a platform that allows the integration of control and elimination programs for different pathogens.
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- 2022
12. Multiplex Antibody Analysis of IgM, IgA and IgG to SARS-CoV-2 in Saliva and Serum from Infected Children and their Close Contacts
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Luis Izquierdo, Laura Puyol, Marta Vidal, María Melé Casas, Victoria Fumadó, Rebeca Santano, Eduard Gratacós, Iolanda Jordan, Mariona Fernández de Sevilla, Alfons Jiménez, Carlota Dobaño, Anna Codina, Marta Cubells, Joana Claverol, María Hernández García, Quique Bassat, Diana Barrios, Carlo Carolis, Carmen Muñoz-Almagro, Gemma Pons Tomas, Juan José García-García, Gemma Moncunill, Rocío Rubio, Aleix Garcia-Miquel, Selena Alonso, Monica Girona-Alarcon, Natalia Rodrigo Melero, Claudia Fortuny, Elisenda Bonet-Carne, and Ruth Aguilar
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Infectivity ,Saliva ,biology ,business.industry ,Context (language use) ,Asymptomatic ,Serology ,Vaccination ,Antigen ,Immunology ,biology.protein ,Medicine ,Antibody ,medicine.symptom ,business - Abstract
COVID-19 affects children to a lesser extent than adults but they can still get infected and transmit SARS-CoV-2 to their contacts. Field deployable non-invasive sensitive diagnostic techniques are needed to evaluate the infectivity dynamics of the coronavirus in pediatric populations and guide public health interventions.We evaluated the utility of high-throughput Luminex-based assays applied to saliva samples to quantify IgM, IgA and IgG antibodies against five SARS-CoV-2 spike (S) and nucleocapsid (N) antigens in the context of a contacts and infectivity longitudinal study. We compared the antibody levels obtained in saliva versus serum/plasma samples from a group of children and adults tested weekly by RT-PCR over 35 days and diagnosed as positive (n=58), and a group of children and adults who consistently tested negative over the follow up period (n=61), in the Summer of 2020 in Barcelona, Spain.Antibody levels in saliva samples from individuals with confirmed RT-PCR diagnosis of SARS-CoV-2 infection were significantly higher than in negative individuals and correlated with those measured in sera/plasmas. Higher levels of anti-S IgG were found in asymptomatic individuals that could indicate protection against disease in infected individuals. Higher anti-S IgG and IgM levels in serum/plasma and saliva, respectively, in infected children compared to infected adults could also be related to stronger clinical immunity in them. Among infected children, males had higher levels of saliva IgG to N and RBD than females. Despite overall correlation, individual clustering analysis suggested that responses that may not be detected in blood could be patent in saliva, and vice versa, and therefore that both measurements are complementary.In addition to serum/plasma, measurement of SARS-CoV-2-specific saliva antibodies should be considered as a complementary non-invasive assay to better estimate the percentage of individuals who have experienced coronavirus infection. Saliva antibody detection could allow determining COVID-19 prevalence in pediatric populations, alternative to bleeding or nasal swab, and serological diagnosis following vaccination.
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- 2021
13. Agreement between commercially available ELISA and in-house Luminex SARS-CoV-2 antibody immunoassays
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Eduard Gratacós, Rebeca Santano, Jordi Chi, Gemma Moncunill, Francesca Crovetto, Carlota Dobaño, Marta Vidal, Diana Barrios, Fatima Crispi, and Luis Izquierdo
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Coronavirus disease 2019 (COVID-19) ,Science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Context (language use) ,Enzyme-Linked Immunosorbent Assay ,medicine.disease_cause ,Antibodies, Viral ,Sensitivity and Specificity ,Immunoglobulin G ,Article ,Serology ,COVID-19 Serological Testing ,Pregnancy ,medicine ,Humans ,Serologic Tests ,Pandemics ,Coronavirus ,Immunoassay ,Multidisciplinary ,biology ,medicine.diagnostic_test ,business.industry ,SARS-CoV-2 ,Diagnostic test ,COVID-19 ,Fetal Blood ,Publisher Correction ,Immunoglobulin A ,Immunoglobulin M ,Viral infection ,Immunology ,biology.protein ,Medicine ,Female ,Antibody ,business - Abstract
Serological diagnostic of the severe respiratory distress syndrome coronavirus 2 (SARS-CoV-2) is a valuable tool for the determination of immunity and surveillance of exposure to the virus. In the context of an ongoing pandemic, it is essential to externally validate widely used tests to assure correct diagnostics and epidemiological estimations. We evaluated the performance of the COVID-19 ELISA IgG and the COVID-19 ELISA IgM/A (Vircell, S.L.) against a highly specific and sensitive in-house Luminex immunoassay in a set of samples from pregnant women and cord blood. The agreement between both assays was moderate to high for IgG but low for IgM/A. Considering seropositivity by either IgG and/or IgM/A, the technical performance of the ELISA was highly imbalanced, with 96% sensitivity at the expense of 22% specificity. As for the clinical performance, the negative predictive value reached 87% while the positive predictive value was 51%. Our results stress the need for highly specific and sensitive assays and external validation of diagnostic tests with different sets of samples to avoid the clinical, epidemiological and personal disturbances derived from serological misdiagnosis.
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- 2021
14. Seven-month kinetics of SARS-CoV-2 antibodies and protective role of pre-existing antibodies to seasonal human coronaviruses on COVID-19
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Laura Puyol, Pere Santamaria, Antoni Trilla, Daniel Parras, Natalia Ortega, Angeline Cruz, Sarah R. Williams, Alfons Jiménez, Pilar Varela, Diana Barrios, Benjamin Trinité, Rebeca Santano, Gemma Moncunill, Pau Serra, Marta Vidal, Marta Ribes, Edwards Pradenas, Luis Izquierdo, Robert A. Mitchell, Carlota Dobaño, Pablo Engel, Natalia Rodrigo, Pablo Hernández-Luis, Neus Rosell, Sonia Barroso, Rocío Rubio, Ana Angulo, Selena Alonso, Chenjerai Jairoce, Marta Tortajada, Montserrat Lamoglia, Ruth Aguilar, Carlo Carolis, Susana Méndez, Alfredo Mayor, Anna Vilella, Alberto L. García-Basteiro, Jordi Chi, Anna Llupià, and Julià Blanco
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biology ,business.industry ,virus diseases ,Common cold ,Disease ,medicine.disease ,Asymptomatic ,Neutralization ,Antigen ,Immunology ,Cohort ,biology.protein ,Medicine ,Seroprevalence ,Antibody ,medicine.symptom ,business - Abstract
Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and its determinants, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E,NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed-up for 6 months (N = 578). Seroprevalence increased over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, were stable over time, except IgG to nucleocapsid antigen and IgM levels that waned. After the peak response, anti-spike antibody levels increased from ∼150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. Pre-existing antibodies to alpha-HCoV were lower in individuals who subsequently seroconverted for SARS-CoV-2. IgG and IgA to HCoV were significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.
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- 2021
15. Ambient Air Pollution in Relation to SARS-CoV-2 Infection, Antibody Response, and COVID-19 Disease: A Cohort Study in Catalonia, Spain (COVICAT Study)
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Ana Espinosa, Marta Cirach, Gemma Moncunill, Gemma Castaño-Vinyals, Mark J. Nieuwenhuijsen, Cathryn Tonne, Anna Carreras, Rebeca Santano, Alfons Jiménez, Ruth Aguilar, Vanessa Pleguezuelos, Rafael de Cid, Rocío Rubio, Beatriz Cortés, Payam Dadvand, Marianna Karachaliou, Carlota Dobaño, Luis Izquierdo, Cristina O'Callaghan-Gordo, Judith Garcia-Aymerich, Laura Puyol, Marta Vidal, Diana Barrios, and Manolis Kogevinas
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2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Ambient air pollution ,SARS-CoV-2 ,business.industry ,Aire--Contaminació ,Research ,Health, Toxicology and Mutagenesis ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Public Health, Environmental and Occupational Health ,COVID-19 ,COVID-19 (Malaltia) -- Catalunya ,Disease ,medicine.disease_cause ,Antibody response ,Air Pollution ,Environmental health ,Humans ,Medicine ,Particulate Matter ,Public Health ,Immunoglobulines ,business ,Cohort study ,Coronavirus - Abstract
Background: emerging evidence links ambient air pollution with coronavirus 2019 (COVID-19) disease, an association that is methodologically challenging to investigate. Objectives: we examined the association between long-term exposure to air pollution with SARS-CoV-2 infection measured through antibody response, level of antibody response among those infected, and COVID-19 disease. Methods: we contacted 9,605 adult participants from a population-based cohort study in Catalonia between June and November 2020; most participants were between 40 and 65 years of age. We drew blood samples from 4,103 participants and measured immunoglobulin M (IgM), IgA, and IgG antibodies against five viral target antigens to establish infection to the virus and levels of antibody response among those infected. We defined COVID-19 disease using self-reported hospital admission, prior positive diagnostic test, or more than three self-reported COVID-19 symptoms after contact with a COVID-19 case. We estimated prepandemic (2018-2019) exposure to fine particulate matter [PM with an aerodynamic diameter of ≤2.5μ m ( PM 2.5 )], nitrogen dioxide ( NO2 ), black carbon (BC), and ozone ( O3 ) at the residential address using hybrid land-use regression models. We calculated log-binomial risk ratios (RRs), adjusting for individual- and area-level covariates. Results: among those tested for SARS-CoV-2 antibodies, 743 (18.1%) were seropositive. Air pollution levels were not statistically significantly associated with SARS-CoV-2 infection: Adjusted RRs per interquartile range were 1.07 (95% CI: 0.97, 1.18) for NO 2, 1.04 (95% CI: 0.94, 1.14) for PM 2.5 , 1.00 (95% CI: 0.92, 1.09) for BC, and 0.97 (95% CI: 0.89, 1.06) for O3. Among infected participants, exposure to NO2 and PM 2.5 were positively associated with IgG levels for all viral target antigens. Among all participants, 481 (5.0%) had COVID-19 disease. Air pollution levels were associated with COVID-19 disease: adjusted RRs = 1.14 (95% CI: 1.00, 1.29) for NO2 and 1.17 (95% CI: 1.03, 1.32) for PM 2.5. Exposure to O3 was associated with a slightly decreased risk (RR = 0.92; 95% CI: 0.83, 1.03). Associations of air pollution with COVID-19 disease were more pronounced for severe COVID-19, with RRs = 1.26 (95% CI: 0.89, 1.79) for NO 2 and 1.51 (95% CI: 1.06, 2.16) for PM 2.5. Discussion: exposure to air pollution was associated with a higher risk of COVID-19 disease and level of antibody response among infected but not with SARS-CoV-2 infection. https://doi.org/10.1289/EHP9726.
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- 2021
16. Immunogenicity and crossreactivity of antibodies to SARS-CoV-2 nucleocapsid protein
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Natalia Rodrigo Melero, Gemma Moncunill, Carlota Dobaño, Rebeca Santano, Alberto L. García-Basteiro, Jordi Chi, Alfons Jiménez, Luis Izquierdo, Ruth Aguilar, Francisco Carmona-Torre, Alfredo Mayor, Marta Vidal, Marta Tortajada, Gabriel Reina, Antoni Torres, Matija Popovic, Laia Fernández-Barat, Rubén López-Aladid, and Carlo Carolis
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biology ,Coronavirus disease 2019 (COVID-19) ,viruses ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunogenicity ,fungi ,virus diseases ,Common cold ,medicine.disease ,Virology ,body regions ,Immunity ,biology.protein ,medicine ,Seroprevalence ,In patient ,Antibody ,skin and connective tissue diseases - Abstract
COVID-19 patients elicit strong responses to the nucleocapsid (N) protein of SARS-CoV-2 but binding antibodies are also detected in prepandemic individuals, indicating potential crossreactivity with common cold human coronaviruses (HCoV) and questioning its utility in seroprevalence studies. We investigated the immunogenicity of the full-length and shorter fragments of the SARS-CoV-2 N protein, and the crossreactivity of antibodies with HCoV. We indentified a C-terminus region in SARS-CoV2 N of minimal sequence homology with HCoV that was more specific and highly immunogenic. IgGs to the full-length SARS-CoV-2 N also recognised N229E N, and IgGs to HKU1 N recognised SARS-CoV-2 N. Crossreactivity with SARS-CoV-2 was stronger for alpha-rather than beta-HCoV despite having less sequence identity, revealing the importance of conformational recognition. Higher preexisting IgG to OC43 N correlated with lower IgG to SARS-CoV-2 in rRT-PCR negative individuals, reflecting less exposure and indicating a potential protective association. Antibodies to SARS-CoV-2 N were higher in patients with more severe and longer symptoms and in females. IgGs remained stable for at least 3 months, while IgAs and IgMs declined faster. In conclusion, N is a primary target of SARS-CoV-2-specific and HCoV crossreactive antibodies, both of which may affect the acquisition of immunity to COVID-19.
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- 2020
17. SARS-CoV-2 infections and antibody responses among health care workers in a Spanish hospital after a month of follow-up
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Rebeca Santano, Natalia Ortega, Jochen Hecht, Sergi Sanz, Angeline Cruz, Alberto L. García-Basteiro, Neus Rosell, Sara Torres, Carlo Carolis, Pilar Varela, Alfons Jiménez, Eugenia Chóliz, M. Martinez, Sonia Barroso, Silvia Fochs, Laura Puyol, Marta Ribes, Patricia Sotomayor, Anna Llupià, Robert A. Mitchell, Javier Rodríguez Moreno, Antoni Trilla, Ruth Aguilar, Gemma Moncunill, Sarah R. Williams, Anna Vilella, Alfredo Mayor, Selena Alonso, Pau Cisteró, Carlota Dobaño, Chenjerai Jairoce, Marta Tortajada, Susana Méndez, Montserrat Lamoglia, Nuria Pey, Diana Barrios, and Marta Vidal
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medicine.medical_specialty ,biology ,business.industry ,Risk of infection ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Subclass ,Antibody response ,Internal medicine ,Health care ,Cohort ,medicine ,biology.protein ,Seroprevalence ,Antibody ,business - Abstract
BackgroundAt the peak of the COVID-19 pandemic in Spain, cumulative prevalence of SARS-CoV-2 infection in a cohort of 578 randomly selected health care workers (HCW) from Hospital Clínic de Barcelona was 11.2%.MethodsA follow-up survey one month after the baseline (April-May 2020) measured SARS-CoV-2 infection by real time reverse-transcriptase polymerase chain reaction (rRT-PCR) and IgM, IgA, IgG and subclasses to the receptor-binding domain of the SARS-CoV-2 spike protein by Luminex. Prevalence of infection was defined by a positive SARS-CoV-2 rRT-PCR and/or antibody seropositivity.ResultsThe cumulative prevalence of infection at month 1 was 14.9% (84/565) and the seroprevalence 14.5% (82/565) for IgM and/or IgG and/or IgA. We found 25 (5%) new infections in participants without previous evidence of infection at baseline (501) and two participants seroreverted for IgM and/or IgG and/or IgA. Among seropositive participants at baseline, IgM and IgA levels generally declined at month 1 (antibody decay rates of 0.49 (95% CI, 0.40-0.60) and 0.34 (95% CI, 0.26-0.44)), respectively. Eight percent of the participants seroreverted for IgM and 11% for IgA. Subjects reporting COVID-19-like symptoms and laboratory and other technicians had higher risk of infection. The most frequent subclass responses were IgG1 and IgG2, followed by IgG3, with higher levels of IgG1, and only IgA1 but no IgA2 was detected.ConclusionsOur findings highlight the importance of a continuous and improved surveillance of SARS-CoV-2 infections in HCW, particularly in high risk groups. The decay of IgA and IgM levels have implications for seroprevalence studies using these isotypes.
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- 2020
18. RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study
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Núria Díez-Padrisa, Chenjerai Jairoce, Nana Aba Williams, Benoit Gamain, Ben Gyan, James G. Beeson, Alfons Jiménez, Evelina Angov, Kwaku Poku Asante, Rebeca Santano, Deepak Gaur, Ruth Aguilar, Aintzane Ayestaran, Clarissa Valim, Ross L. Coppel, David Dosoo, Seth Owusu-Agyei, Joseph J. Campo, David E. Lanar, Itziar Ubillos, Marta Vidal, David R. Cavanagh, Augusto Nhabomba, Virander S. Chauhan, Sheetij Dutta, Carlota Dobaño, Gemma Moncunill, Chetan E. Chitnis, Universitat de Barcelona (UB), Centro de Investigação em Saúde de Manhiça [Maputo, Mozambique] (CISM), University of Ghana, Kintampo Health Research Centre, Ghana, CIBER de Epidemiología y Salud Pública (CIBERESP), Walter Reed Army Institute of Research, International Centre for Genetic Engineering and Biotechnology [New Delhi] (ICGEB), Biologie de Plasmodium et Vaccins - Malaria Parasite Biology and Vaccines, Institut Pasteur [Paris], Jawaharlal Nehru University (JNU), Department of Immunology and Infectious Diseases (IID), Harvard T.H. Chan School of Public Health, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Monash University [Melbourne], University of Edinburgh, The Macfarlane Burnet Institute for Medical Research and Public Health [Melbourne], Funding was obtained from the NIH-NIAID (R01AI095789), PATH Malaria Vaccine Initiative (MVI), Ministerio de Economía y Competitividad (Instituto de Salud Carlos III, PI11/00423 and PI14/01422), and EVIMalaR and AGAUR-Catalonia (2014 SGR991). GM was a recipient of a Sara Borrell—ISCIII fellowship (CD010/00156) and had the support of the Department of Health, Catalan Government (SLT006/17/00109). ISGlobal is a member of the CERCA Program, Generalitat de Catalunya., Biologie de Plasmodium et Vaccins, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), Institut Pasteur [Paris] (IP), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)
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Male ,lcsh:Medicine ,Antibodies, Protozoan ,0302 clinical medicine ,Pre-erythrocytic antigens ,antibody ,RTS,S ,Medicine ,030212 general & internal medicine ,Malaria, Falciparum ,Child ,Children ,Protection ,biology ,Malaria vaccine ,Vaccination ,General Medicine ,Acquired immune system ,protection ,3. Good health ,Blood-stage antigens ,Child, Preschool ,Female ,Infants ,Research Article ,Naturally acquired immunity ,Plasmodium falciparum ,malaria ,Malària ,Àfrica ,Antigens, Protozoan ,RTS ,03 medical and health sciences ,Immune system ,Antigen ,parasitic diseases ,Malaria Vaccines ,Humans ,Antibody ,Maternal antibodies ,business.industry ,lcsh:R ,Infant ,biology.organism_classification ,medicine.disease ,Malaria ,maternal antibodies ,Case-Control Studies ,Immunology ,Africa ,Antibody Formation ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology ,business ,Vaccine ,030217 neurology & neurosurgery - Abstract
Background Vaccination and naturally acquired immunity against microbial pathogens may have complex interactions that influence disease outcomes. To date, only vaccine-specific immune responses have routinely been investigated in malaria vaccine trials conducted in endemic areas. We hypothesized that RTS,S/A01E immunization affects acquisition of antibodies to Plasmodium falciparum antigens not included in the vaccine and that such responses have an impact on overall malaria protective immunity. Methods We evaluated IgM and IgG responses to 38 P. falciparum proteins putatively involved in naturally acquired immunity to malaria in 195 young children participating in a case-control study nested within the African phase 3 clinical trial of RTS,S/AS01E (MAL055 NCT00866619) in two sites of different transmission intensity (Kintampo high and Manhiça moderate/low). We measured antibody levels by quantitative suspension array technology and applied regression models, multimarker analysis, and machine learning techniques to analyze factors affecting their levels and correlates of protection. Results RTS,S/AS01E immunization decreased antibody responses to parasite antigens considered as markers of exposure (MSP142, AMA1) and levels correlated with risk of clinical malaria over 1-year follow-up. In addition, we show for the first time that RTS,S vaccination increased IgG levels to a specific group of pre-erythrocytic and blood-stage antigens (MSP5, MSP1 block 2, RH4.2, EBA140, and SSP2/TRAP) which levels correlated with protection against clinical malaria (odds ratio [95% confidence interval] 0.53 [0.3–0.93], p = 0.03, for MSP1; 0.52 [0.26–0.98], p = 0.05, for SSP2) in multivariable logistic regression analyses. Conclusions Increased antibody responses to specific P. falciparum antigens in subjects immunized with this partially efficacious vaccine upon natural infection may contribute to overall protective immunity against malaria. Inclusion of such antigens in multivalent constructs could result in more efficacious second-generation multistage vaccines. Electronic supplementary material The online version of this article (10.1186/s12916-019-1378-6) contains supplementary material, which is available to authorized users.
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- 2019
19. A balanced pro-inflammatory and regulatory cytokine signature in young African children is associated with lower risk of clinical malaria
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Rebeca Santano, Tamara Katherine Berthoud, Alfons Jiménez, Llorenç Quintó, Caterina Guinovart, Pedro L. Alonso, Maria N. Manaca, John J. Aponte, Ruth Aguilar, Arnoldo Barbosa, Carlota Dobaño, Denise L. Doolan, Penny L Groves, Quique Bassat, Augusto Nhabomba, Mauricio H. Rodríguez, and Universitat de Barcelona
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0301 basic medicine ,Cell Extracts ,Erythrocytes ,Lymphocyte ,medicine.medical_treatment ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,030212 general & internal medicine ,Malaria, Falciparum ,Articles and Commentaries ,Children ,Mozambique ,biology ,Artemisinins ,Infectious Diseases ,medicine.anatomical_structure ,Cytokine ,Pyrimethamine ,Child, Preschool ,Chemoprophylaxis ,Cytokines ,Infants ,Microbiology (medical) ,030106 microbiology ,Schizonts ,Malària ,Àfrica ,Chemoprevention ,Proinflammatory cytokine ,03 medical and health sciences ,Antimalarials ,Double-Blind Method ,Immunity ,Sulfadoxine ,medicine ,Humans ,Inflammation ,business.industry ,Infant, Newborn ,Infant ,Plasmodium falciparum ,biology.organism_classification ,medicine.disease ,Malaria ,chemistry ,Artesunate ,Immunology ,Africa ,Leukocytes, Mononuclear ,business ,Transcriptome - Abstract
Background The effect of timing of exposure to first Plasmodium falciparum infections during early childhood on the induction of innate and adaptive cytokine responses and their contribution to the development of clinical malaria immunity is not well established. Methods As part of a double-blind, randomized, placebo-controlled trial in Mozambique using monthly chemoprophylaxis with sulfadoxine-pyrimethamine plus artesunate to selectively control timing of malaria exposure during infancy, peripheral blood mononuclear cells collected from participants at age 2.5, 5.5, 10.5, 15, and 24 months were stimulated ex vivo with parasite schizont and erythrocyte lysates. Cytokine messenger RNA expressed in cell pellets and proteins secreted in supernatants were quantified by reverse-transcription quantitative polymerase chain reaction and multiplex flow cytometry, respectively. Children were followed up for clinical malaria from birth until 4 years of age. Results Higher proinflammatory (interleukin [IL] 1, IL-6, tumor necrosis factor) and regulatory (IL-10) cytokine concentrations during the second year of life were associated with reduced incidence of clinical malaria up to 4 years of age, adjusting by chemoprophylaxis and prior malaria exposure. Significantly lower concentrations of antigen-specific T-helper 1 (IL-2, IL-12, interferon-γ) and T-helper 2 (IL-4, IL-5) cytokines by 2 years of age were measured in children undergoing chemoprophylaxis compared to children receiving placebo (P < .03). Conclusions Selective chemoprophylaxis altering early natural exposure to malaria blood stage antigens during infancy had a significant effect on T-helper lymphocyte cytokine production >1 year later. Importantly, a balanced proinflammatory and anti-inflammatory cytokine signature, probably by innate cells, around age 2 years was associated with protective clinical immunity during childhood. Clinical Trials Registration NCT00231452.
- Published
- 2018
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