Serial SARS-CoV-2 Receptor-Binding Domain Antibody Responses in Patients Receiving Dialysis

We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.

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A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

10.1101/2020.08.31.275701 ◽

2020 ◽

Author(s):

Tiong Kit Tan ◽

Pramila Rijal ◽

Rolle Rahikainen ◽

Anthony H. Keeble ◽

Lisa Schimanski ◽

...

Keyword(s):

Antibody Response ◽

Receptor Binding ◽

Polyclonal Antibody ◽

Vaccine Candidate ◽

Binding Domain ◽

Antibody Responses ◽

Cold Chain ◽

Receptor Binding Domain ◽

Cell Infection ◽

Protein Receptor

ABSTRACTThere is dire need for an effective and affordable vaccine against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a modular virus-like particle vaccine candidate displaying the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) using SpyTag/SpyCatcher technology (RBD-SpyVLP). Low doses of RBD-SpyVLP in a prime-boost regimen induced a strong neutralising antibody response in mice and pigs that was superior to convalescent human sera. We evaluated antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we showed that RBD-SpyVLP induced a polyclonal antibody response that recognised all key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. The induction of potent and polyclonal antibody responses by RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic. Moreover, RBD-SpyVLP is highly resilient, thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence.

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Anti-SARS-CoV-2 receptor binding domain antibody evolution after mRNA vaccination

Nature ◽

10.1038/s41586-021-04060-7 ◽

2021 ◽

Author(s):

Alice Cho ◽

Frauke Muecksch ◽

Dennis Schaefer-Babajew ◽

Zijun Wang ◽

Shlomo Finkin ◽

...

Keyword(s):

Receptor Binding ◽

Binding Domain ◽

Receptor Binding Domain ◽

Domain Antibody

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Monoclonal Antibody Responses after Recombinant Hemagglutinin Vaccine versus Subunit Inactivated Influenza Virus Vaccine: a Comparative Study

Journal of Virology ◽

10.1128/jvi.01150-19 ◽

2019 ◽

Vol 93 (21) ◽

Cited By ~ 3

Author(s):

Carole Henry ◽

Anna-Karin E. Palm ◽

Henry A. Utset ◽

Min Huang ◽

Irvin Y. Ho ◽

...

Keyword(s):

Influenza Virus ◽

Receptor Binding ◽

Mammalian Cells ◽

Influenza Virus Infection ◽

Binding Domain ◽

Antibody Responses ◽

Surface Glycoprotein ◽

Immune Memory ◽

Receptor Binding Domain ◽

Production Strategies

ABSTRACT Vaccination is the best measure of protection against influenza virus infection. Vaccine-induced antibody responses target mainly the hemagglutinin (HA) surface glycoprotein, composed of the head and the stalk domains. Recently two novel vaccine platforms have been developed for seasonal influenza vaccination: a recombinant HA vaccine produced in insect cells (Flublok) and Flucelvax, prepared from virions produced in mammalian cells. In order to compare the fine specificity of the antibodies induced by these two novel vaccine platforms, we characterized 42 Flublok-induced monoclonal antibodies (MAbs) and 38 Flucelvax-induced MAbs for avidity, cross-reactivity, and any selectivity toward the head versus the stalk domain. These studies revealed that Flublok induced a greater proportion of MAbs targeting epitopes near the receptor-binding domain on HA head (hemagglutinin inhibition-positive MAbs) than Flucelvax, while the two vaccines induced similar low frequencies of stalk-reactive MAbs. Finally, mice immunized with Flublok and Flucelvax also induced similar frequencies of stalk-reactive antibody-secreting cells, showing that HA head immunodominance is independent of immune memory bias. Collectively, our results suggest that these vaccine formulations are similarly immunogenic but differ in the preferences of the elicited antibodies toward the receptor-binding domain on the HA head. IMPORTANCE There are ongoing efforts to increase the efficacy of influenza vaccines and to promote production strategies that can rapidly respond to newly emerging viruses. It is important to understand if current alternative seasonal vaccines, such as Flublok and Flucelvax, that use alternate production strategies can induce protective influenza-specific antibodies and to evaluate what type of epitopes are targeted by distinct vaccine formulations.

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Binding and Neutralizing Antibody Responses to SARS-CoV-2 in Infants and Young Children Exceed Those in Adults

10.1101/2021.12.20.21268034 ◽

2021 ◽

Author(s):

Ruth A. Karron ◽

Maria Garcia Quesada ◽

Elizabeth A. Schappell ◽

Stephen D. Schmidt ◽

Maria Deloria Knoll ◽

...

Keyword(s):

Young Children ◽

Immune Responses ◽

Receptor Binding ◽

Neutralizing Antibody ◽

Binding Domain ◽

Antibody Responses ◽

Receptor Binding Domain ◽

Binding Antibody ◽

Infants And Young Children

SARS-CoV-2 infections are frequently milder in children than adults, suggesting that immune responses may vary with age. However, information is limited regarding SARS-CoV-2 immune responses in young children. We compared Receptor Binding Domain binding antibody (RBDAb) and SARS-CoV-2 neutralizing antibody (neutAb) in children aged 0-4 years, 5-17 years, and in adults aged 18-62 years in a SARS-CoV-2 household study. Among 55 participants seropositive at enrollment, children aged 0-4 years had >10-fold higher RBDAb titers than adults (373 vs.35, P<0.0001), and the highest RBDAb titers in 11/12 households with seropositive children and adults. Children aged 0-4 years had 2-fold higher neutAb than adults, resulting in higher binding to neutralizing (B/N)Ab ratios compared to adults (1.9 vs. 0.4 for ID50, P=0.0002). Findings suggest that young children mount robust antibody responses to SARS-CoV-2 following community infections. Additionally, these results support using neutAb to measure the immunogenicity of COVID-19 vaccines in children aged 0-4 years.

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