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  1. Article: SARS-CoV-2 Viral Load in the Pulmonary Compartment of Critically Ill COVID-19 Patients Correlates with Viral Serum Load and Fatal Outcomes

    Ynga-Durand, Mario / Maaß, Henrike / Milošević, Marko / Krstanović, Fran / Pribanić Matešić, Marina / Jonjić, Stipan / Protić, Alen / Brizić, Ilija / Šustić, Alan / Čičin-Šain, Luka

    Viruses. 2022 June 14, v. 14, no. 6

    2022  

    Abstract: While SARS-CoV-2 detection in sputum and swabs from the upper respiratory tract has been used as a diagnostic tool, virus quantification showed poor correlation to disease outcome and thus, poor prognostic value. Although the pulmonary compartment ... ...

    Abstract While SARS-CoV-2 detection in sputum and swabs from the upper respiratory tract has been used as a diagnostic tool, virus quantification showed poor correlation to disease outcome and thus, poor prognostic value. Although the pulmonary compartment represents a relevant site for viral load analysis, limited data exploring the lower respiratory tract is available, and its association to clinical outcomes is relatively unknown. Using bronchoalveolar lavage (BAL) and serum samples, we quantified SARS-CoV-2 copy numbers in the pulmonary and systemic compartments of critically ill patients admitted to the intensive care unit of a COVID-19 referral hospital in Croatia during the second and third pandemic waves. Clinical data, including 30-day survival after ICU admission, were included. We found that elevated SARS-CoV-2 copy numbers in both BAL and serum samples were associated with fatal outcomes. Remarkably, the highest and earliest viral loads after initiation of mechanical ventilation support were increased in the non-survival group. Our results imply that viral loads in the lungs contribute to COVID-19 disease severity, while blood titers correlate with lung virus titers, albeit at a lower level. Moreover, they suggest that BAL SARS-CoV-2 copy number quantification at ICU admission may provide a predictive parameter of clinical COVID-19 outcomes.
    Keywords COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; blood serum ; diagnostic techniques ; hospitals ; lungs ; pandemic ; viral load ; viruses ; Croatia
    Language English
    Dates of publication 2022-0614
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14061292
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells.

    Rožmanić, Carmen / Lisnić, Berislav / Pribanić Matešić, Marina / Mihalić, Andrea / Hiršl, Lea / Park, Eugene / Lesac Brizić, Ana / Indenbirken, Daniela / Viduka, Ina / Šantić, Marina / Adler, Barbara / Yokoyama, Wayne M / Krmpotić, Astrid / Juranić Lisnić, Vanda / Jonjić, Stipan / Brizić, Ilija

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 6412

    Abstract: Infections in early life can elicit substantially different immune responses and pathogenesis than infections in adulthood. Here, we investigate the consequences of murine cytomegalovirus infection in newborn mice on NK cells. We show that infection ... ...

    Abstract Infections in early life can elicit substantially different immune responses and pathogenesis than infections in adulthood. Here, we investigate the consequences of murine cytomegalovirus infection in newborn mice on NK cells. We show that infection severely compromised NK cell maturation and functionality in newborns. This effect was not due to compromised virus control. Inflammatory responses to infection dysregulated the expression of major transcription factors governing NK cell fate, such as Eomes, resulting in impaired NK cell function. Most prominently, NK cells from perinatally infected mice have a diminished ability to produce IFN-γ due to the downregulation of long non-coding RNA Ifng-as1 expression. Moreover, the bone marrow's capacity to efficiently generate new NK cells is reduced, explaining the prolonged negative effects of perinatal infection on NK cells. This study demonstrates that viral infections in early life can profoundly impact NK cell biology, including long-lasting impairment in NK cell functionality.
    MeSH term(s) Mice ; Animals ; Killer Cells, Natural ; Cytomegalovirus Infections/genetics ; Muromegalovirus
    Language English
    Publishing date 2023-10-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-42182-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: SARS-CoV-2 Viral Load in the Pulmonary Compartment of Critically Ill COVID-19 Patients Correlates with Viral Serum Load and Fatal Outcomes.

    Ynga-Durand, Mario / Maaß, Henrike / Milošević, Marko / Krstanović, Fran / Pribanić Matešić, Marina / Jonjić, Stipan / Protić, Alen / Brizić, Ilija / Šustić, Alan / Čičin-Šain, Luka

    Viruses

    2022  Volume 14, Issue 6

    Abstract: While SARS-CoV-2 detection in sputum and swabs from the upper respiratory tract has been used as a diagnostic tool, virus quantification showed poor correlation to disease outcome and thus, poor prognostic value. Although the pulmonary compartment ... ...

    Abstract While SARS-CoV-2 detection in sputum and swabs from the upper respiratory tract has been used as a diagnostic tool, virus quantification showed poor correlation to disease outcome and thus, poor prognostic value. Although the pulmonary compartment represents a relevant site for viral load analysis, limited data exploring the lower respiratory tract is available, and its association to clinical outcomes is relatively unknown. Using bronchoalveolar lavage (BAL) and serum samples, we quantified SARS-CoV-2 copy numbers in the pulmonary and systemic compartments of critically ill patients admitted to the intensive care unit of a COVID-19 referral hospital in Croatia during the second and third pandemic waves. Clinical data, including 30-day survival after ICU admission, were included. We found that elevated SARS-CoV-2 copy numbers in both BAL and serum samples were associated with fatal outcomes. Remarkably, the highest and earliest viral loads after initiation of mechanical ventilation support were increased in the non-survival group. Our results imply that viral loads in the lungs contribute to COVID-19 disease severity, while blood titers correlate with lung virus titers, albeit at a lower level. Moreover, they suggest that BAL SARS-CoV-2 copy number quantification at ICU admission may provide a predictive parameter of clinical COVID-19 outcomes.
    MeSH term(s) COVID-19 ; Critical Illness ; Humans ; Lung ; SARS-CoV-2 ; Viral Load
    Language English
    Publishing date 2022-06-14
    Publishing country Switzerland
    Document type Journal Article ; 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/v14061292
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Collection of Monoclonal Antibodies Targeting SARS-CoV-2 Proteins

    Pribanić Matešić, Marina / Kučan Brlić, Paola / Lenac Roviš, Tihana / Mačak Šafranko, Željka / Chaouat, Abigael Eva / Miklić, Karmela / Malić, Suzana / Ivanković, Nina / Schubert, Maren / Bertoglio, Federico / Markotić, Alemka / Mandelboim, Ofer / Jonjić, Stipan / Brizić, Ilija

    Viruses. 2022 Feb. 21, v. 14, no. 2

    2022  

    Abstract: In early 2020, the COVID-19 pandemic sparked a global crisis that continues to pose a serious threat to human health and the economy. Further advancement in research is necessary and requires the availability of quality molecular tools, including ... ...

    Abstract In early 2020, the COVID-19 pandemic sparked a global crisis that continues to pose a serious threat to human health and the economy. Further advancement in research is necessary and requires the availability of quality molecular tools, including monoclonal antibodies. Here, we present the development and characterization of a collection of over 40 new monoclonal antibodies directed against different SARS-CoV-2 proteins. Recombinant SARS-CoV-2 proteins were expressed, purified, and used as immunogens. Upon development of specific hybridomas, the obtained monoclonal antibody (mAb) clones were tested for binding to recombinant proteins and infected cells. We generated mAbs against structural proteins, the Spike and Nucleocapsid protein, several non-structural proteins (nsp1, nsp7, nsp8, nsp9, nsp10, nsp16) and accessory factors (ORF3a, ORF9b) applicable in flow cytometry, immunofluorescence, or Western blot. Our collection of mAbs provides a set of novel, highly specific tools that will allow a comprehensive analysis of the viral proteome, which will allow further understanding of SARS-CoV-2 pathogenesis and the design of therapeutic strategies.
    Keywords COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; Western blotting ; antigens ; flow cytometry ; fluorescent antibody technique ; human health ; hybridomas ; monoclonal antibodies ; nucleocapsid proteins ; pathogenesis ; proteome ; therapeutics
    Language English
    Dates of publication 2022-0221
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14020443
    Database NAL-Catalogue (AGRICOLA)

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  5. Article: The Virus-Induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members Are Not Required for Efficient Replication of HSV-1

    Zubković, Andreja / Žarak, Ines / Ratkaj, Ivana / Rokić, Filip / Jekić, Maja / Pribanić Matešić, Marina / Lebrón, Ricardo / Gómez-Martín, Cristina / Lisnić, Berislav / Lisnić, Vanda Juranić / Jonjić, Stipan / Pan, Dongli / Vugrek, Oliver / Hackenberg, Michael / Jurak, Igor

    Viruses. 2022 July 28, v. 14, no. 8

    2022  

    Abstract: Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of the regulation of efficient virus ... ...

    Abstract Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of the regulation of efficient virus replication. In this study, we comprehensively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182, are reproducibly deregulated during productive infection. These miRNAs are predicted to regulate a great number of potential targets involved in different cellular processes and have only 33 shared targets. Among these, members of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover, these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.
    Keywords Human alphaherpesvirus 1 ; microRNA ; virus replication ; viruses
    Language English
    Dates of publication 2022-0728
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14081661
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: The Virus-Induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members Are Not Required for Efficient Replication of HSV-1.

    Zubković, Andreja / Žarak, Ines / Ratkaj, Ivana / Rokić, Filip / Jekić, Maja / Pribanić Matešić, Marina / Lebrón, Ricardo / Gómez-Martín, Cristina / Lisnić, Berislav / Lisnić, Vanda Juranić / Jonjić, Stipan / Pan, Dongli / Vugrek, Oliver / Hackenberg, Michael / Jurak, Igor

    Viruses

    2022  Volume 14, Issue 8

    Abstract: Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of the regulation of efficient virus ... ...

    Abstract Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of the regulation of efficient virus replication. In this study, we comprehensively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182, are reproducibly deregulated during productive infection. These miRNAs are predicted to regulate a great number of potential targets involved in different cellular processes and have only 33 shared targets. Among these, members of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover, these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.
    MeSH term(s) Herpes Simplex/genetics ; Herpesvirus 1, Human/physiology ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Up-Regulation ; Virus Replication
    Chemical Substances MIRN183 microRNA, human ; MicroRNAs
    Language English
    Publishing date 2022-07-28
    Publishing country Switzerland
    Document type Journal Article ; 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/v14081661
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Collection of Monoclonal Antibodies Targeting SARS-CoV-2 Proteins.

    Pribanić Matešić, Marina / Kučan Brlić, Paola / Lenac Roviš, Tihana / Mačak Šafranko, Željka / Chaouat, Abigael Eva / Miklić, Karmela / Malić, Suzana / Ivanković, Nina / Schubert, Maren / Bertoglio, Federico / Markotić, Alemka / Mandelboim, Ofer / Jonjić, Stipan / Brizić, Ilija

    Viruses

    2022  Volume 14, Issue 2

    Abstract: In early 2020, the COVID-19 pandemic sparked a global crisis that continues to pose a serious threat to human health and the economy. Further advancement in research is necessary and requires the availability of quality molecular tools, including ... ...

    Abstract In early 2020, the COVID-19 pandemic sparked a global crisis that continues to pose a serious threat to human health and the economy. Further advancement in research is necessary and requires the availability of quality molecular tools, including monoclonal antibodies. Here, we present the development and characterization of a collection of over 40 new monoclonal antibodies directed against different SARS-CoV-2 proteins. Recombinant SARS-CoV-2 proteins were expressed, purified, and used as immunogens. Upon development of specific hybridomas, the obtained monoclonal antibody (mAb) clones were tested for binding to recombinant proteins and infected cells. We generated mAbs against structural proteins, the Spike and Nucleocapsid protein, several non-structural proteins (nsp1, nsp7, nsp8, nsp9, nsp10, nsp16) and accessory factors (ORF3a, ORF9b) applicable in flow cytometry, immunofluorescence, or Western blot. Our collection of mAbs provides a set of novel, highly specific tools that will allow a comprehensive analysis of the viral proteome, which will allow further understanding of SARS-CoV-2 pathogenesis and the design of therapeutic strategies.
    MeSH term(s) Angiotensin-Converting Enzyme 2/genetics ; Antibodies, Monoclonal/classification ; Antibodies, Monoclonal/pharmacology ; Antibodies, Viral/immunology ; Antibodies, Viral/pharmacology ; COVID-19/therapy ; COVID-19/virology ; HEK293 Cells ; Humans ; Recombinant Proteins/immunology ; SARS-CoV-2/chemistry ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Viral Proteins/antagonists & inhibitors
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Viral ; Recombinant Proteins ; Spike Glycoprotein, Coronavirus ; Viral Proteins ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Language English
    Publishing date 2022-02-21
    Publishing country Switzerland
    Document type Journal Article ; 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/v14020443
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: ChAdOx1-S adenoviral vector vaccine applied intranasally elicits superior mucosal immunity compared to the intramuscular route of vaccination.

    Cokarić Brdovčak, Maja / Materljan, Jelena / Šustić, Marko / Ravlić, Sanda / Ružić, Tina / Lisnić, Berislav / Miklić, Karmela / Brizić, Ilija / Pribanić Matešić, Marina / Juranić Lisnić, Vanda / Halassy, Beata / Rončević, Dobrica / Knežević, Zdravka / Štefan, Leo / Bertoglio, Federico / Schubert, Maren / Čičin-Šain, Luka / Markotić, Alemka / Jonjić, Stipan /
    Krmpotić, Astrid

    European journal of immunology

    2022  Volume 52, Issue 6, Page(s) 936–945

    Abstract: COVID-19 vaccines prevent severe forms of the disease, but do not warrant complete protection against breakthrough infections. This could be due to suboptimal mucosal immunity at the site of virus entry, given that all currently approved vaccines are ... ...

    Abstract COVID-19 vaccines prevent severe forms of the disease, but do not warrant complete protection against breakthrough infections. This could be due to suboptimal mucosal immunity at the site of virus entry, given that all currently approved vaccines are administered via the intramuscular route. In this study, we assessed humoral and cellular immune responses in BALB/c mice after intranasal and intramuscular immunization with adenoviral vector ChAdOx1-S expressing full-length Spike protein of SARS-CoV-2. We showed that both routes of vaccination induced a potent IgG antibody response, as well as robust neutralizing capacity, but intranasal vaccination elicited a superior IgA antibody titer in the sera and in the respiratory mucosa. Bronchoalveolar lavage from intranasally immunized mice efficiently neutralized SARS-CoV-2, which has not been the case in intramuscularly immunized group. Moreover, substantially higher percentages of epitope-specific CD8 T cells exhibiting a tissue resident phenotype were found in the lungs of intranasally immunized animals. Finally, both intranasal and intramuscular vaccination with ChAdOx1-S efficiently protected the mice after the challenge with recombinant herpesvirus expressing the Spike protein. Our results demonstrate that intranasal application of adenoviral vector ChAdOx1-S induces superior mucosal immunity and therefore could be a promising strategy for putting the COVID-19 pandemic under control.
    MeSH term(s) Adenoviridae/genetics ; Administration, Intranasal ; Animals ; Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Immunity, Cellular ; Immunity, Mucosal ; Mice ; Mice, Inbred BALB C ; Pandemics/prevention & control ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Vaccination/methods ; Viral Vaccines
    Chemical Substances Antibodies, Viral ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; Viral Vaccines ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-03-31
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.202249823
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Human serum from SARS-CoV-2-vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant.

    Schubert, Maren / Bertoglio, Federico / Steinke, Stephan / Heine, Philip Alexander / Ynga-Durand, Mario Alberto / Maass, Henrike / Sammartino, Josè Camilla / Cassaniti, Irene / Zuo, Fanglei / Du, Likun / Korn, Janin / Milošević, Marko / Wenzel, Esther Veronika / Krstanović, Fran / Polten, Saskia / Pribanić-Matešić, Marina / Brizić, Ilija / Baldanti, Fausto / Hammarström, Lennart /
    Dübel, Stefan / Šustić, Alan / Marcotte, Harold / Strengert, Monika / Protić, Alen / Piralla, Antonio / Pan-Hammarström, Qiang / Čičin-Šain, Luka / Hust, Michael

    BMC medicine

    2022  Volume 20, Issue 1, Page(s) 102

    Abstract: Background: The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and immediately classified as a variant of concern (VOC), since it shows substantially more mutations in the spike ... ...

    Abstract Background: The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and immediately classified as a variant of concern (VOC), since it shows substantially more mutations in the spike protein than any previous variant, especially in the receptor-binding domain (RBD). We analyzed the binding of the Omicron RBD to the human angiotensin-converting enzyme-2 receptor (ACE2) and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta, or Delta RBD variants.
    Methods: All RBDs were produced in insect cells. RBD binding to ACE2 was analyzed by ELISA and microscale thermophoresis (MST). Similarly, sera from 27 COVID-19 patients, 81 vaccinated individuals, and 34 booster recipients were titrated by ELISA on RBDs from the original Wuhan strain, Beta, Delta, and Omicron VOCs. In addition, the neutralization efficacy of authentic SARS-CoV-2 wild type (D614G), Delta, and Omicron by sera from 2× or 3× BNT162b2-vaccinated persons was analyzed.
    Results: Surprisingly, the Omicron RBD showed a somewhat weaker binding to ACE2 compared to Beta and Delta, arguing that improved ACE2 binding is not a likely driver of Omicron evolution. Serum antibody titers were significantly lower against Omicron RBD compared to the original Wuhan strain. A 2.6× reduction in Omicron RBD binding was observed for serum of 2× BNT162b2-vaccinated persons. Neutralization of Omicron SARS-CoV-2 was completely diminished in our setup.
    Conclusion: These results indicate an immune escape focused on neutralizing antibodies. Nevertheless, a boost vaccination increased the level of anti-RBD antibodies against Omicron, and neutralization of authentic Omicron SARS-CoV-2 was at least partially restored. This study adds evidence that current vaccination protocols may be less efficient against the Omicron variant.
    MeSH term(s) BNT162 Vaccine ; COVID-19/prevention & control ; Humans ; Pandemics ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/genetics
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; BNT162 Vaccine (N38TVC63NU)
    Language English
    Publishing date 2022-03-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2131669-7
    ISSN 1741-7015 ; 1741-7015
    ISSN (online) 1741-7015
    ISSN 1741-7015
    DOI 10.1186/s12916-022-02312-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Human serum from SARS-CoV-2 vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant in comparison to the original Wuhan strain and the Beta and Delta variants

    Schubert, Maren / Bertoglio, Federico / Steinke, Stephan / Heine, Philip Alexander / Ynga-Durand, Mario Alberto / Zuo, Fanglei / Du, Likun / Korn, Janin / Milosevic, Marko / Wenzel, Esther Veronika / Maass, Henrike / Krstanovic, Fran / Polten, Saskia / Pribanic-Matesic, Marina / Brizic, Ilija / Piralla, Antonio / Baldanti, Fausto / Hammarstrom, Lennart / Dubel, Stefan /
    Sustic, Alan / Marcotte, Harold / Strengert, Monika / Protic, Alen / Pan Hammarstrom, Qiang / Cicin-Sain, Luka / Hust, Michael

    medRxiv

    Abstract: Background The ongoing COVID-19 pandemic is caused by the beta coronavirus SARS-CoV-2. COVID-19 manifests itself from mild or even asymptomatic infections to severe forms of life-threatening pneumonia. At the end of November 2021, yet another novel SARS- ... ...

    Abstract Background The ongoing COVID-19 pandemic is caused by the beta coronavirus SARS-CoV-2. COVID-19 manifests itself from mild or even asymptomatic infections to severe forms of life-threatening pneumonia. At the end of November 2021, yet another novel SARS-CoV-2 variant named B.1.1.529 or Omicron was discovered and classified as a variant of concern (VoC) by the WHO. Omicron shows significantly more mutations in the amino acid (aa) sequence of its spike protein than any previous variant, with the majority of those concentrated in the receptor binding domain (RBD). In this work, the binding of the Omicron RBD to the human ACE2 receptor was experimentally analyzed in comparison to the original Wuhan SARS-CoV-2 virus, and the Beta and Delta variants. Moreover, we compared the ability of human sera from COVID-19 convalescent donors and persons fully vaccinated with BNT162b2 (Corminaty) or Ad26.COV2.S (Janssen COVID-19 vaccine) as well as individuals who had boost vaccine doses with BNT162b2 or mRNA-1273 (Spikevax) to bind the different RBDs variants. Methods The Omicron RBD with 15 aa mutations compared to the original Wuhan strain was produced baculovirus-free in insect cells. Binding of the produced Omicron RBD to hACE was analyzed by ELISA. Sera from 27 COVID-19 patients, of whom 21 were fully vaccinated and 16 booster recipients were titrated on the original Wuhan strain, Beta, Delta and Omicron RBD and compared to the first WHO International Standard for anti-SARS-CoV-2 immunoglobulin (human) using the original Wuhan strain as reference. Results The Omicron RBD showed a slightly reduced binding to ACE2 compared to the other RBDs. The serum of COVID-19 patients, BNT162b2 vaccinated and boost vaccinated persons showed a reduced binding to Omicron RBD in comparison to the original Wuhan strain, Beta und Delta RBDs. In this assay, the boost vaccination did not improve the RBD binding when compared to the BNT162b2 fully vaccinated group. The RBD binding of the Ad26.COV2.S serum group was lower at all compared to the other groups. Conclusions The reduced binding of human sera to Omicron RBD provides first hints that the current vaccinations using BNT162b2, mRNA-1273 and Ad26.COV2.S may be less efficient in preventing infections with the Omicron variant.
    Keywords covid19
    Language English
    Publishing date 2021-12-13
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.12.10.21267523
    Database COVID19

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