scholarly journals Sex Disparities and Neutralizing-Antibody Durability to SARS-CoV-2 Infection in Convalescent Individuals

mSphere ◽  
2021 ◽  
Vol 6 (4) ◽  
Author(s):  
Alena J. Markmann ◽  
Natasa Giallourou ◽  
D. Ryan Bhowmik ◽  
Yixuan J. Hou ◽  
Aaron Lerner ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Antibody Titers ◽  
Sex Disparities ◽  
Binding Antibody ◽  
Male Sex ◽  
Antibody Levels

In this study, we found that neutralizing antibody responses in COVID-19-convalescent individuals vary in magnitude but are durable and correlate well with receptor binding domain (RBD) Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex.

scholarly journals Sex disparities and neutralizing antibody durability to SARS-CoV-2 infection in convalescent individuals

2021 ◽  
Author(s):  
Alena J. Markmann ◽  
Natasa Giallourou ◽  
D. Ryan Bhowmik ◽  
Yixuan J. Hou ◽  
Aaron Lerner ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Human Antibody ◽  
Antibody Titers ◽  
Sex Disparities ◽  
Binding Antibody ◽  
Male Sex ◽  
Antibody Levels ◽  
First Time

AbstractThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2. Using convalescent sera collected from 101 COVID-19 recovered individuals 21-212 days after symptom onset with forty-eight additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations between individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to six months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex. We also show that SARS-CoV-2 convalescent neutralizing antibodies are higher in individuals with cardio-metabolic comorbidities.SignificanceIn this study we found that neutralizing antibody responses in COVID-19 convalescent individuals vary in magnitude but are durable and correlate well with RBD Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time, that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardio-metabolic co-morbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2.

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

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.

scholarly journals High titers of multiple antibody isotypes against the SARS-CoV-2 spike receptor-binding domain and nucleoprotein associate with better neutralization

2020 ◽  
Author(s):  
Maria G. Noval ◽  
Maria E. Kaczmarek ◽  
Akiko Koide ◽  
Bruno A. Rodriguez-Rodriguez ◽  
Ping Louie ◽  
...  
Keyword(s):  
Antibody Response ◽  
Receptor Binding ◽  
Healthcare Workers ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Pseudotyped Virus ◽  
Receptor Binding Domain ◽  
Neutralization Capacity ◽  
Antibody Isotypes ◽  
Antibody Titers

AbstractUnderstanding antibody responses to SARS-CoV-2 is indispensable for the development of containment measures to overcome the current COVID-19 pandemic. Here, we determine the ability of sera from 101 recovered healthcare workers to neutralize both authentic SARS-CoV-2 and SARS-CoV-2 pseudotyped virus and address their antibody titers against SARS-CoV-2 nucleoprotein and spike receptor-binding domain. Interestingly, the majority of individuals have low neutralization capacity and only 6% of the healthcare workers showed high neutralizing titers against both authentic SARS-CoV-2 virus and the pseudotyped virus. We found the antibody response to SARS-CoV-2 infection generates antigen-specific isotypes as well as a diverse combination of antibody isotypes, with high titers of IgG, IgM and IgA against both antigens correlating with neutralization capacity. Importantly, we found that neutralization correlated with antibody titers as quantified by ELISA. This suggests that an ELISA assay can be used to determine seroneutralization potential. Altogether, our work provides a snapshot of the SARS-CoV-2 neutralizing antibody response in recovered healthcare workers and provides evidence that possessing multiple antibody isotypes may play an important role in SARS-CoV-2 neutralization.

scholarly journals Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cesheng Li ◽  
Ding Yu ◽  
Xiao Wu ◽  
Hong Liang ◽  
Zhijun Zhou ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Immune Memory ◽  
Strong Positive Correlation ◽  
Receptor Binding Domain ◽  
Igg Antibody ◽  
Humoral Immune ◽  
Positive Rate ◽  
Antibody Titers

AbstractTo investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.

scholarly journals Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

2021 ◽  
Vol 118 (38) ◽  
pp. e2106433118
Author(s):  
Hannah A. D. King ◽  
M. Gordon Joyce ◽  
Ines Lakhal-Naouar ◽  
Aslaa Ahmed ◽  
Camila Macedo Cincotta ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
High Dose ◽  
Receptor Binding Domain ◽  
Rapid Control ◽  
Novel Variants ◽  
Antibody Titers ◽  
Respiratory Challenge

Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 µg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV−like Sarbecovirus vaccine development.

scholarly journals Differential serological and neutralizing antibody dynamics after an infection by a single SARS-CoV-2 strain

2020 ◽  
Author(s):  
Emmanuelle Billon-Denis ◽  
Audrey Ferrier-Rembert ◽  
Annabelle Garnier ◽  
Laurence Cheutin ◽  
Clarisse Vigne ◽  
...  
Keyword(s):  
Immune Response ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Clinical Severity ◽  
Individual Factors ◽  
Receptor Binding Domain ◽  
Antibody Titers ◽  
Antibody Dynamics

Abstract BackgroundWe report here the case of two coworkers infected by the same SARS-CoV-2 strain, presenting two different immunological outcomes. CaseOne patient presented a strong IgG anti-receptor-binding domain immune response correlated with a low and rapidly decreasing titer of neutralizing antibodies. The other patient had similar strong IgG anti-receptor-binding domain immune response but high neutralizing antibody titers. Discussion and ConclusionThus, host individual factors may be the main drivers of the immune response varying with age and clinical severity.

scholarly journals Induction of Potent and Durable Neutralizing Antibodies Against SARS-CoV-2 Using a Receptor Binding Domain-Based Immunogen

2021 ◽  
Vol 12 ◽  
Author(s):  
Vikram Srivastava ◽  
Ling Niu ◽  
Kruttika S. Phadke ◽  
Bryan H. Bellaire ◽  
Michael W. Cho
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Global Economy ◽  
Severe Pneumonia ◽  
Binding Domain ◽  
Effective Vaccine ◽  
Receptor Binding Domain ◽  
Neutralization Titer ◽  
Antibody Titers ◽  
Binding Antibody

A novel betacoronavirus (SARS-CoV-2) that causes severe pneumonia emerged through zoonosis in late 2019. The disease, referred to as COVID-19, has an alarming mortality rate and it is having a devastating effect on the global economy and public health systems. A safe, effective vaccine is urgently needed to halt this pandemic. In this study, immunogenicity of the receptor binding domain (RBD) of spike (S) glycoprotein was examined in mice. Animals were immunized with recombinant RBD antigen intraperitoneally using three different adjuvants (Zn-chitosan, Alhydrogel, and Adju-Phos), and antibody responses were followed for over 5 months. Results showed that potent neutralizing antibodies (nAbs) can be induced with 70% neutralization titer (NT70) of ~14,580 against live, infectious viruses. Although antigen-binding antibody titers decreased gradually over time, sufficiently protective levels of nAbs persisted (NT80 &gt;2,430) over the 5-month observation period. Results also showed that adjuvants have profound effects on kinetics of nAb induction, total antibody titers, antibody avidity, antibody longevity, and B-cell epitopes targeted by the immune system. In conclusion, a recombinant subunit protein immunogen based on the RBD is a highly promising vaccine candidate. Continued evaluation of RBD immunogenicity using different adjuvants and vaccine regimens could further improve vaccine efficacy.

scholarly journals Receptor-Binding Domain Proteins of SARS-CoV-2 Variants Elicited Robust Antibody Responses Cross-Reacting with Wild-Type and Mutant Viruses in Mice

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1383
Author(s):  
Juan Shi ◽  
Xiaoxiao Jin ◽  
Yan Ding ◽  
Xiaotao Liu ◽  
Anran Shen ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Polyclonal Antibodies ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Neutralization Capacity ◽  
Antibody Titers ◽  
High Level

Multiple variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have spread around the world, but the neutralizing effects of antibodies induced by the existing vaccines have declined, which highlights the importance of developing vaccines against mutant virus strains. In this study, nine receptor-binding domain (RBD) proteins of the SARS-CoV-2 variants (B.1.1.7, B.1.351 and P.1 lineages) were constructed and fused with the Fc fragment of human IgG (RBD-Fc). These RBD-Fc proteins contained single or multiple amino acid substitutions at prevalent mutation points of spike protein, which enabled them to bind strongly to the polyclonal antibodies specific for wild-type RBD and to the recombinant human ACE2 protein. In the BALB/c, mice were immunized with the wild-type RBD-Fc protein first and boosted twice with the indicated mutant RBD-Fc proteins later. All mutant RBD-Fc proteins elicited high-level IgG antibodies and cross-neutralizing antibodies. The RBD-Fc proteins with multiple substitutions tended to induce higher antibody titers and neutralizing-antibody titers than the single-mutant RBD-Fc proteins. Meanwhile, both wild-type RBD-Fc protein and mutant RBD-Fc proteins induced significantly decreased neutralization capacity to the pseudovirus of B.1.351 and P.1 lineages than to the wild-type one. These data will facilitate the design and development of RBD-based subunit vaccines against SARS-COV-2 and its variants.

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