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Article ; Online: Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo.

Sitnik, Katarzyna M / Krstanović, Fran / Gödecke, Natascha / Rand, Ulfert / Kubsch, Tobias / Maaß, Henrike / Kim, Yeonsu / Brizić, Ilija / Čičin-Šain, Luka

Nature communications

2023 Volume 14, Issue 1, Page(s) 3087

Abstract: To date, no herpesvirus has been shown to latently persist in fibroblastic cells. Here, we show that murine cytomegalovirus, a β-herpesvirus, persists for the long term and across organs in PDGFRα-positive fibroblastic cells, with similar or higher ... ...

Abstract	To date, no herpesvirus has been shown to latently persist in fibroblastic cells. Here, we show that murine cytomegalovirus, a β-herpesvirus, persists for the long term and across organs in PDGFRα-positive fibroblastic cells, with similar or higher genome loads than in the previously known sites of murine cytomegalovirus latency. Whereas murine cytomegalovirus gene transcription in PDGFRα-positive fibroblastic cells is almost completely silenced at 5 months post-infection, these cells give rise to reactivated virus ex vivo, arguing that they support latent murine cytomegalovirus infection. Notably, PDGFRα-positive fibroblastic cells also support productive virus replication during primary murine cytomegalovirus infection. Mechanistically, Stat1-deficiency promotes lytic infection but abolishes latent persistence of murine cytomegalovirus in PDGFRα-positive fibroblastic cells in vivo. In sum, fibroblastic cells have a dual role as a site of lytic murine cytomegalovirus replication and a reservoir of latent murine cytomegalovirus in vivo and STAT1 is required for murine cytomegalovirus latent persistence in vivo.
MeSH term(s)	Animals ; Mice ; Cytomegalovirus/genetics ; Cytomegalovirus Infections ; Muromegalovirus ; Virus Latency/genetics ; Receptor, Platelet-Derived Growth Factor alpha ; Virus Replication ; Fibroblasts ; STAT1 Transcription Factor/genetics
Chemical Substances	Receptor, Platelet-Derived Growth Factor alpha (EC 2.7.10.1) ; Stat1 protein, mouse ; STAT1 Transcription Factor
Language	English
Publishing date	2023-05-29
Publishing country	England
Document type	Journal Article ; 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/s41467-023-38449-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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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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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 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
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Article ; Online: SARS-CoV-2 Seroprevalence in Germany.

Gornyk, Daniela / Harries, Manuela / Glöckner, Stephan / Strengert, Monika / Kerrinnes, Tobias / Heise, Jana-Kristin / Maaß, Henrike / Ortmann, Julia / Kessel, Barbora / Kemmling, Yvonne / Lange, Berit / Krause, Gérard

Deutsches Arzteblatt international

2022 Volume 118, Issue 48, Page(s) 824–831

Abstract: Background: Until now, information on the spread of SARS-CoV-2 infections in Germany has been based mainly on data from the public health offices. It may be assumed that these data do not include many cases of asymptomatic and mild infection.: Methods! ...

Abstract	Background: Until now, information on the spread of SARS-CoV-2 infections in Germany has been based mainly on data from the public health offices. It may be assumed that these data do not include many cases of asymptomatic and mild infection. Methods: We determined seroprevalence over the course of the pandemic in a sequential, multilocal seroprevalence study (MuSPAD). Study participants were recruited at random in seven administrative districts (Kreise) in Germany from July 2020 onward; each participant was tested at two different times 3-5 months apart. Test findings on blood samples were used to determine the missed-case rate of reported infections, the infection fatality rate (IFR), and the association between seropositivity and demographic, socio-economic, and health-related factors, as well as to evaluate the self-reported results of PCR and antigenic tests. The registration number of this study is DRKS00022335. Results: Among non-vaccinated persons, the seroprevalence from July to December 2020 was 1.3-2.8% and rose between February and May 2021 to 4.1-13.1%. In July 2021, 35% of tested persons in Chemnitz were not vaccinated, and the seroprevalence among these persons was 32.4% (07/2021). The surveillance detection ratio (SDR), i.e., the ratio between the true number of infections estimated from seroprevalence and the actual number or reported infections, varied among the districts included in the study from 2.2 to 5.1 up to December 2020 and from 1.3 to 2.9 up to June 2021, and subsequently declined. The IFR was in the range of 0.8% to 2.4% in all regions except Magdeburg, where a value of 0.3% was calculated for November 2020. A lower educational level was associated with a higher seropositivity rate, smoking with a lower seropositivity rate. On average, 1 person was infected for every 8.5 persons in quarantine. Conclusion: Seroprevalence was low after the first wave of the pandemic but rose markedly during the second and third waves. The missed-case rate trended downward over the course of the pandemic.
MeSH term(s)	COVID-19 ; Germany/epidemiology ; Humans ; Pandemics ; SARS-CoV-2 ; Seroepidemiologic Studies
Language	English
Publishing date	2022-01-05
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2406159-1
ISSN	1866-0452 ; 1866-0452
ISSN (online)	1866-0452
ISSN	1866-0452
DOI	10.3238/arztebl.m2021.0364
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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
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Article ; Online: Diminished neutralization responses towards SARS-CoV-2 Omicron VoC after mRNA or vector-based COVID-19 vaccinations.

Jacobsen, Henning / Strengert, Monika / Maaß, Henrike / Ynga Durand, Mario Alberto / Katzmarzyk, Maeva / Kessel, Barbora / Harries, Manuela / Rand, Ulfert / Abassi, Leila / Kim, Yeonsu / Lüddecke, Tatjana / Metzdorf, Kristin / Hernandez, Pilar / Ortmann, Julia / Heise, Jana-Kristin / Castell, Stefanie / Gornyk, Daniela / Glöckner, Stephan / Melhorn, Vanessa /

Kemmling, Yvonne / Lange, Berit / Dulovic, Alex / Marsall, Patrick / Häring, Julia / Junker, Daniel / Schneiderhan-Marra, Nicole / Hoffmann, Markus / Pöhlmann, Stefan / Krause, Gérard / Cicin-Sain, Luka

Scientific reports

2022 Volume 12, Issue 1, Page(s) 19858

Abstract: SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection against infection. The novel variant of concern (VoC) Omicron BA.1 and its sub-lineages have the largest number of amino acid alterations in ...

Abstract	SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection against infection. The novel variant of concern (VoC) Omicron BA.1 and its sub-lineages have the largest number of amino acid alterations in its Spike protein to date. Thus, they may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals in particular in those who have only received a primary immunization scheme. We analyzed neutralization activity of sera from individuals after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe by in vitro neutralization assay at peak response towards SARS-CoV-2 B.1, Omicron sub-lineages BA.1, BA.2, BA.2.12.1, BA.3, BA.4/5, Beta and Delta pseudotypes and also provide longitudinal follow-up data from BNT162b2 vaccinees. All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (96-100%) towards the SARS-CoV-2 B.1 isolate, and minor to moderate reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant and its sub-lineages had the biggest impact, both in terms of response rates and neutralization titers. Only mRNA-1273 showed a 100% response rate to Omicron BA.1 and induced the highest level of neutralizing antibody titers, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination, vector-based AZD1222 and Ad26.CoV2.S performed less well with peak responder rates of 48%, 56% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up indicating that individuals with cross-protection against Omicron maintain it over time. Overall, our data strongly argue for booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based primary immunization scheme.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; Neutralization Tests ; Antibodies, Viral ; COVID-19 Vaccines ; RNA, Messenger ; Ad26COVS1 ; BNT162 Vaccine ; COVID-19/prevention & control ; ChAdOx1 nCoV-19 ; Vaccination
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; RNA, Messenger ; Ad26COVS1 (JT2NS6183B) ; BNT162 Vaccine ; ChAdOx1 nCoV-19 (B5S3K2V0G8)
Language	English
Publishing date	2022-11-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-22552-y
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Article ; Online: SARS-CoV-2 seroprevalence in Germany - a population based sequential study in five regions

Gornyk, Daniela / Harries, Manuela / Gloeckner, Stephan / Strengert, Monika / Kerrinnes, Tobias / Bojara, Gerhard / Castell, Stefanie / Frank, Kerstin / Gubbe, Knut / Heise, Jana-Kristin / Hernandez, Pilar / Kappert, Oliver / Kern, Winfried / Illig, Thomas / Klopp, Norman / Maass, Henrike / Ortmann, Julia / Kessel, Barbora / Roller, Gottfried /

Schlueter, Monike / Tonn, Torsten / Ziemons, Micheal / Kemmling, Yvonne / Lange, Berit / Krause, Gerard

medRxiv

Abstract: Prevalence of SARS-CoV-2 antibodies is an essential indicator to guide measures. Few population-based estimates are available in Germany. We determine seroprevalence allowing comparison between regions, time points, socio-demographic and health-related ... ...

Abstract	Prevalence of SARS-CoV-2 antibodies is an essential indicator to guide measures. Few population-based estimates are available in Germany. We determine seroprevalence allowing comparison between regions, time points, socio-demographic and health-related factors. MuSPAD is a sequential multi-local seroprevalence study. We randomly recruited adults in five counties with differing cumulative SARS-CoV-2 incidence July 2020 - February 2021. Serostatus was determined using Spike S1-specific IgG ELISA. We determined county-wise proportions of seropositivity. We assessed underestimation of infections, county and age specific infection fatality risks, and association of seropositivity with demographic, socioeconomic and health factors. We found seroprevalence of 2.4 % (95%CI: 1.8-3.1%) for Reutlingen in June 2020 (stage 1) which increased to 2.9% (95%CI: 2.1-3.8%) in October (stage 2), Freiburg stage 1 1.5% (95% CI: 1.1-2.1%) vs. 2.5% (95%CI: 1.8-3.4%), Aachen stage 1 2.3% (95% CI: 1.7-3.1%) vs. 5.4% (95%CI: 4.4-6.6%), Osnabrueck 1.3% (95% CI: 1.0-1.9%) and Magdeburg in Nov/Dec 2020. 2.4% (95%CI 1.9-3.1%). Number needed to quarantine to prevent one infection was 8.2. The surveillance detection ratio (SDR) between number of infections based on our results and number reported to health authorities ranged from 2.5-4.5. Participants aged 80+ had lower SDR. Infection fatality estimates ranged from 0.2-2.4%. Lower education was associated with higher, smoking with lower seropositivity. Seroprevalence remained low until December 2020 with high underdetection. The second wave from November 2020 to February 2021 resulted in additional 2-5% of the population being infected. Detected age specific differences of SDR should be taken into account in modelling and forecasting COVID-19 morbidity. Funding: The Helmholtz Association, European Union9s Horizon 2020 research and innovation programme [grant number 101003480] and intramural funds of the Helmholtz Centre for infection (HZI).
Keywords	covid19
Language	English
Publishing date	2021-05-06
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.05.04.21256597
Database	COVID19

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Article ; Online: Diminished neutralization responses towards SARS-CoV-2 Omicron VoC after mRNA or vector-based COVID-19 vaccinations

Jacobsen, Henning / Strengert, Monika / Maass, Henrike / Ynga Durand, Mario Alberto / Kessel, Barbora / Harries, Manuela / Rand, Ulfert / Abassi, Leila / Kim, Yeonsu / Lueddecke, Tatjana / Hernandez, Pilar / Ortmann, Julia / Heise, Jana-Kristin / Castell, Stefanie / Gornyk, Daniela / Gloeckner, Stephan / Melhorn, Vanessa / Lange, Berit / Dulovic, Alex /

Haering, Julia / Junker, Daniel / Schneiderhan-Marra, Nicole / Poehlmann, Stefan / Hoffmann, Markus / Krause, Gerard / Cicin-Sain, Luka

medRxiv

Abstract: Background: SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection. The novel variant of concern Omicron (B.1.1.529) has to date the largest number of amino acid alterations in its Spike protein. ...

Abstract	Background: SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection. The novel variant of concern Omicron (B.1.1.529) has to date the largest number of amino acid alterations in its Spike protein. Thus, it may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals. Aims: We analysed neutralization activity after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe at peak response and in a longitudinal follow-up with BNT162b2 vaccinees to define immune escape potential of the Omicron VoC. Methods: We tested sera by in vitro neutralization assay towards SARS-CoV-2 B.1, Omicron, Beta and Delta pseudotypes Results: All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (93.3-100%) towards SARS-CoV-2 wild-type, but some reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant had the biggest impact, both in terms of response rates and neutralization titres among responders. Only mRNA-1273 showed a 100% response rate to Omicron and induced the highest titres of neutralizing antibodies, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination or vector-based formulations with AZD1222 or Ad26.CoV2.S performed less well with peak responder rates of 33%, 50% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up and even slightly increased to 47%, indicating cross-protection against Omicron is maintained over time. Conclusions: Overall, our data strongly argues for urgent booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based immunization scheme.
Keywords	covid19
Language	English
Publishing date	2021-12-21
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.12.21.21267898
Database	COVID19

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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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Article ; Online: Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo.

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

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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.

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Article ; Online: SARS-CoV-2 Seroprevalence in Germany.

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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.

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Article ; Online: Diminished neutralization responses towards SARS-CoV-2 Omicron VoC after mRNA or vector-based COVID-19 vaccinations.

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Article ; Online: SARS-CoV-2 seroprevalence in Germany - a population based sequential study in five regions

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Article ; Online: Diminished neutralization responses towards SARS-CoV-2 Omicron VoC after mRNA or vector-based COVID-19 vaccinations

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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

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