Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods

Bošnjak, Berislav; Stein, Saskia C.; Willenzon, Stefanie; Cordes, Anna-Lena; Puppe, Wolfram; Bernhardt, Günter; Ravens, Inga; Ritter, Christiane; Schultze-Florey, Christian; Gödecke, Nina; Martens, Jörg; Kleine-Weber, Hannah; Hoffmann, Markus; Cossmann, Anne; Yılmaz, Mustafa; Pink, Isabelle; Hoeper, Marius M.; Behrens, Georg M. N.; Pöhlmann, Stefan; Blasczyk, Rainer; Schulz, Thomas F.; Förster, Reinhold

doi:10.1038/s41423-020-00573-9

Cited by 113 publications

(122 citation statements)

References 44 publications

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“…For SARS-CoV-2 neutralizing antibodies we found a strong correlation between the results obtained from authentic virus neutralization (PRNT50, VNT100) and the data from surrogate neutralization (sVNT). These data corroborate the findings of a recent study comparing this high-throughput sVNT assay to a pseudotyped virus neutralization assay based on SARS-CoV-2 S protein-carrying vesicular stomatitis virus(25).The i.m. immunizations of BALB/c mice with low and high-dose MVA-SARS-2-S induced robust and nearly equal amounts of SARS-S-specific CD8+ T cells in prime and prime-boost vaccination.…”

supporting

confidence: 89%

“…3D). We obtained similar results when testing the sera in a recently established high-throughput surrogate virus neutralization test for SARS CoV-2 (sVNT) (25) . After the boost immunizations on day 21, we detected levels of surrogate neutralizing antibodies with mean titers of 400 (4/6 seropositive mice, LD) and 840 (6/6, HD) ( In addition, using SARS-2-S derived peptides with predicted capacity for MHC II binding we also monitored the presence of activated CD4+ T cells.…”

Section: Resultsmentioning

confidence: 57%

“…Surrogate virus neutralization assay (sVNT). To test for the presence of neutralizing anti-SARS-CoV-2-S serum antibodies we used surrogate virus neutralization test as described before with slight modifications(25). Briefly, 6 ng of SARS-CoV-2 S RBD (Trenzyme) was pre-incubated for 1 hour at 37 °C with heat-inactivated test sera at final dilutions between 1:20 to 1:540, as indicated on the graphs.…”

mentioning

confidence: 99%

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Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA SARS 2 S in preclinical vaccination

Tscherne

Schwarz²,

Rohde

et al. 2021

Preprint

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The severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavirus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evaluation with our vector vaccine based on vaccinia virus MVA against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here, we describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust synthesis of S antigen, make it a suitable candidate vaccine for industrial scale production. Vaccinated mice produced S antigen-specific CD8+ T cells and serum antibodies binding to S glycoprotein that neutralized SARS-CoV-2. Prime-boost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19.Significance StatementThe highly attenuated vaccinia virus MVA is licensed as smallpox vaccine, and as vector it is a component of the approved Adenovirus-MVA-based prime-boost vaccine against Ebola virus disease. Here we provide results from testing the COVID-19 candidate vaccine MVA-SARS-2-S, a poxvirus-based vector vaccine that proceeded to clinical evaluation. When administered by intramuscular inoculation, MVA-SARS-2-S expresses and safely delivers the full-length SARS-CoV-2 spike (S) protein, inducing balanced SARS-CoV-2-specific cellular and humoral immunity, and protective efficacy in vaccinated mice. Substantial clinical experience has already been gained with MVA vectors using homologous and heterologous prime-boost applications, including the immunization of children and immunocompromised individuals. Thus, MVA-SARS-2-S represents an important resource for developing further optimized COVID-19 vaccines.

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supporting

confidence: 89%

Section: Resultsmentioning

confidence: 57%

mentioning

confidence: 99%

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Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA SARS 2 S in preclinical vaccination

Tscherne

Schwarz²,

Rohde

et al. 2021

Preprint

Self Cite

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“…It is assumed that both the humoral and cellular immune response have an impact on the severity. Most convalescents show detectable anti-SARS-CoV-2 IgG antibody levels between 10 and 21 days after infection [8]. However, there is evidence that some people, primarily those showing a mild progression, exhibit a delayed humorous response or even show no seroconversion at all [9].…”

Section: Introductionmentioning

confidence: 99%

Evidence of long-lasting humoral and cellular immunity against SARS-CoV-2 even in elderly COVID-19 convalescents showing a mild to moderate disease progression

Fischer

Lindenkamp

Lichtenberg

et al. 2021

Preprint

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After the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in China in late 2019, a pandemic evolved that has claimed millions of lives so far. While about 80 % of infections cause mild or moderate COVID-19 disease, some individuals show a severe progression or even die. Most countries are far from achieving herd-immunity, however, the first approved vaccines offer hope for containment of the virus. Although much is known about the virus, there is a lack of information on the immunity of convalescent individuals. We here evaluate the humoral and cellular immune response against SARS-CoV-2 in 41 COVID-19 convalescents. As previous studies mostly included younger individuals, one advantage of our study is the comparatively high mean age of the convalescents included in the cohort considered (54 ± 8.4 years). While anti-SARS-CoV-2 antibodies were still detectable in 95 % of convalescents up to 8 months post infection, an antibody-decay over time was generally observed in most donors. Using a multiplex assay, our data additionally reveal that most convalescents exhibit a broad humoral immunity against different viral epitopes. We demonstrate by flow cytometry that convalescent donors show a significantly elevated number of natural killer cells when compared to healthy controls, while no differences were found concerning other leucocyte subpopulations. We detected a specific long-lasting cellular immune response in convalescents by stimulating immune cells with SARS-CoV-2-specific peptides, covering domains of the viral spike, membrane and nucleocapsid protein, and measuring interferon-γ (IFN-γ) release thereafter. We modified a commercially available ELISA assay for IFN-γ determination in whole-blood specimens of COVID-19 convalescents. One advantage of this assay is that it does not require special equipment and can, thus, be performed in any standard laboratory. In conclusion, our study adds knowledge regarding the persistence of immunity of convalescents suffering from mild to moderate COVID-19. Moreover, our study provides a set of simple methods to characterize and confirm experienced COVID-19.

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“…Higher titers of SARS-CoV-2 specific neutralizing antibodies have been associated with higher COVID-19 severity [6,7]. However, beyond neutralization, antibodies can elicit an array of Fc-mediated innate immune functions such as antibody-dependent complement deposition (ADCD), antibody-dependent cellular phagocytosis (ADCP), and antibodydependent cell-mediated cytotoxicity (ADCC) [8].…”

Section: Introductionmentioning

confidence: 99%

COVID-19 Severity Is Associated with Differential Antibody Fc-mediated Innate Immune Functions

Adeniji

Giron

Zilberstein

et al. 2021

Preprint

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Beyond neutralization, antibodies elicit several innate immune functions including complement deposition (ADCD), phagocytosis (ADCP), and cytotoxicity (ADCC). These functions can be both beneficial (by clearing pathogens) and/or detrimental (by inducing inflammation). We tested the possibility that qualitative differences in SARS-CoV-2 specific antibody-mediated innate immune functions contribute to Coronavirus disease 2019 (COVID-19) severity. We found that antibodies from hospitalized COVID-19 patients elicited higher ADCD but lower ADCP compared to antibodies from non-hospitalized COVID-19 patients. Consistently, higher ADCD was associated with higher systemic inflammation during COVID-19. Our study points to qualitative, differential features of anti-SARS-CoV-2 antibodies as potential contributors to COVID-19 severity.

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Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods

Cited by 113 publications

References 44 publications

Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA SARS 2 S in preclinical vaccination

Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA SARS 2 S in preclinical vaccination

Evidence of long-lasting humoral and cellular immunity against SARS-CoV-2 even in elderly COVID-19 convalescents showing a mild to moderate disease progression

COVID-19 Severity Is Associated with Differential Antibody Fc-mediated Innate Immune Functions

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