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

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.

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

10.1101/2021.04.05.437224 ◽

2021 ◽

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 conducted a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and tested specific antibody response. 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. RBD-IgG kinetics displayed a gradually downward trend, the titer started to stabilize after 9 months and decreased by 68.1% compared with the 1st month. Moreover, male plasma donors produced more RBD-IgG than female plasma donors and patient age positively correlated with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers was also identified. This study is essential for understanding SARS-CoV-2-induced immune memory to develop vaccine and therapeutics.

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Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1707304114 ◽

2017 ◽

Vol 114 (35) ◽

pp. E7348-E7357 ◽

Cited By ~ 282

Author(s):

Jesper Pallesen ◽

Nianshuang Wang ◽

Kizzmekia S. Corbett ◽

Daniel Wrapp ◽

Robert N. Kirchdoerfer ◽

...

Keyword(s):

Receptor Binding ◽

Case Fatality ◽

Neutralizing Antibody ◽

Human Populations ◽

Receptor Binding Domain ◽

Potential Mechanism ◽

Primary Target ◽

Humoral Immune ◽

Receptor Recognition ◽

Antibody Titers

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.

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

10.1101/2020.08.15.252353 ◽

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.

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2106433118 ◽

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.

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

10.21203/rs.3.rs-77625/v1 ◽

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.

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

Vaccines ◽

10.3390/vaccines9121383 ◽

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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Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice

Viruses ◽

10.3390/v12090987 ◽

2020 ◽

Vol 12 (9) ◽

pp. 987 ◽

Cited By ~ 2

Author(s):

Andrea N. Loes ◽

Lauren E. Gentles ◽

Allison J. Greaney ◽

Katharine H. D. Crawford ◽

Jesse D. Bloom

Keyword(s):

Influenza Virus ◽

Receptor Binding ◽

Neutralizing Antibodies ◽

Reverse Genetics ◽

Natural Infection ◽

Neutralizing Antibody ◽

Binding Domain ◽

Effective Vaccine ◽

Receptor Binding Domain ◽

Antibody Titers

An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.

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

mSphere ◽

10.1128/msphere.00275-21 ◽

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.

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Efficacy of ancestral receptor-binding domain, S1 and trimeric spike protein vaccines against SARS-CoV-2 variants B.1.1.7, B.1.351, and B.1.617.1

10.1101/2021.06.02.446698 ◽

2021 ◽

Author(s):

Yong Yang ◽

Jinkai Zang ◽

Shiqi Xu ◽

Xueyang Zhang ◽

Sule Yuan ◽

...

Keyword(s):

Receptor Binding ◽

Immune Escape ◽

Neutralizing Antibody ◽

Prototype Strain ◽

Binding Domain ◽

Receptor Binding Domain ◽

S Protein ◽

Antibody Titers ◽

Continued Use

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current SARS-CoV-2 vaccines are based on spike (S) protein, S1 subunit, or receptor-binding domain (RBD) of prototype strain. Emergence of several novel SARS-CoV-2 variants has raised concern about potential immune escape. In this study, we performed an immunogenicity comparison of ancestral RBD, S1, and S ectodomain trimer (S-trimer) antigens and tested the efficacy of these prototype vaccines against the circulating variants, especially B.1.617 that has been linked to India's current COVID-19 surge. We found that RBD and S-trimer proteins could induce significantly higher neutralizing antibody titers than S1 protein. For the three vaccines, the neutralizing titers decreased over time, but still remained high for at least five months after immunization. Importantly, the three prototype vaccines were still effective in neutralizing the variants of concern, although B.1.351 and B.1.617.1 lineages showed varying degrees of reduction in neutralization by the immune sera. The vaccines-induced sera were shown to block receptor binding and inhibit S protein-mediated membrane fusion. In addition, the immune sera did not promote antibody-dependent enhancement (ADE) in vitro. Our work provides valuable information for development of SARS-CoV-2 subunit vaccines and also supports the continued use of ancestral RBD or S-based vaccines to fight the COVID-19 epidemic.

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Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice

10.1101/2020.08.12.248823 ◽

2020 ◽

Author(s):

Andrea N. Loes ◽

Lauren E. Gentles ◽

Allison J. Greaney ◽

Katharine H. D. Crawford ◽

Jesse D. Bloom

Keyword(s):

Influenza Virus ◽

Receptor Binding ◽

Neutralizing Antibodies ◽

Reverse Genetics ◽

Natural Infection ◽

Neutralizing Antibody ◽

Binding Domain ◽

Effective Vaccine ◽

Receptor Binding Domain ◽

Antibody Titers

AbstractAn effective vaccine is essential to controlling the spread of SARS-CoV-2 virus. Here, we describe an influenza-virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 Spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (∼1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for production of influenza vaccines.

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