scholarly journals The recombinant subunit vaccine RBD-Fc, consisting of SARS-CoV-2 RBD and human IgG Fc as an immunopotentiator, elicits robust neutralizing antibody responses against SARS-CoV-2 infection

2020 ◽  
Author(s):  
Zezhong Liu ◽  
Wei Xu ◽  
Shuai Xia ◽  
Chenjian Gu ◽  
Xinling Wang ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
High Titer ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Human Igg ◽  
Specific Antibodies ◽  
Good Potential ◽  
Neutralizing Epitopes

Abstract The pandemic of COVID-19 caused by SARS-CoV-2 has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to ACE2 receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.

scholarly journals RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Zezhong Liu ◽  
Wei Xu ◽  
Shuai Xia ◽  
Chenjian Gu ◽  
Xinling Wang ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
High Titer ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Angiotensin Converting Enzyme 2 ◽  
Specific Antibodies ◽  
Good Potential ◽  
Neutralizing Epitopes

AbstractThe pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.

scholarly journals Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals

2020 ◽  
Author(s):  
Davide F. Robbiani ◽  
Christian Gaebler ◽  
Frauke Muecksch ◽  
Julio C. C. Lorenzi ◽  
Zijun Wang ◽  
...  
Keyword(s):  
Virus Entry ◽  
Protein S ◽  
Memory B Cells ◽  
Antibody Responses ◽  
Spike Protein ◽  
Human Antibody ◽  
Receptor Binding Domain ◽  
Single Digit ◽  
Specific Antibodies ◽  
Specific Memory

AbstractDuring the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21–5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

scholarly journals A single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice

2020 ◽  
Author(s):  
Abigail E. Powell ◽  
Kaiming Zhang ◽  
Mrinmoy Sanyal ◽  
Shaogeng Tang ◽  
Payton A. Weidenbacher ◽  
...  
Keyword(s):  
Single Dose ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Amino Acid Deletion ◽  
Vaccine Candidates ◽  
Self Assembling ◽  
Antibody Titers

AbstractDevelopment of a safe and effective SARS-CoV-2 vaccine is a public health priority. We designed subunit vaccine candidates using self-assembling ferritin nanoparticles displaying one of two multimerized SARS-CoV-2 spikes: full-length ectodomain (S-Fer) or a C-terminal 70 amino-acid deletion (SΔC-Fer). Ferritin is an attractive nanoparticle platform for production of vaccines and ferritin-based vaccines have been investigated in humans in two separate clinical trials. We confirmed proper folding and antigenicity of spike on the surface of ferritin by cryo-EM and binding to conformation-specific monoclonal antibodies. After a single immunization of mice with either of the two spike ferritin particles, a lentiviral SARS-CoV-2 pseudovirus assay revealed mean neutralizing antibody titers at least 2-fold greater than those in convalescent plasma from COVID-19 patients. Additionally, a single dose of SΔC-Fer elicited significantly higher neutralizing responses as compared to immunization with the spike receptor binding domain (RBD) monomer or spike ectodomain trimer alone. After a second dose, mice immunized with SΔC-Fer exhibited higher neutralizing titers than all other groups. Taken together, these results demonstrate that multivalent presentation of SARS-CoV-2 spike on ferritin can notably enhance elicitation of neutralizing antibodies, thus constituting a viable strategy for single-dose vaccination against COVID-19.

scholarly journals Coronavirus-Specific Antibody Cross Reactivity in Rhesus Macaques Following SARS-CoV-2 Vaccination and Infection

2021 ◽  
Author(s):  
Catherine Jacob-Dolan ◽  
Jared Feldman ◽  
Katherine McMahan ◽  
Jingyou Yu ◽  
Roland Zahn ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Specific Antibody ◽  
Rhesus Macaques ◽  
Rapid Development ◽  
Neutralizing Antibody ◽  
Cross Reactivity ◽  
Antibody Responses ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Before And After

Vaccines are being rapidly developed with the goal of ending the SARS-CoV-2 pandemic. However, the extent to which SARS-CoV-2 vaccination induces serum responses that cross-react with other coronaviruses remains poorly studied. Here we define serum profiles in rhesus macaques after vaccination with DNA or Ad26 based vaccines expressing SARS-CoV-2 Spike protein followed by SARS-CoV-2 challenge, or SARS-CoV-2 infection alone. Analysis of serum responses showed robust reactivity to the SARS-CoV-2 full-length Spike protein and receptor binding domain (RBD), both included in the vaccine. However, serum cross-reactivity to the closely related sarbecovirus SARS-CoV-1 Spike and RBD, was reduced. Reactivity was also measured to the distantly related common cold alpha-coronavirus, 229E and NL63, and beta-coronavirus, OC43 and HKU1, Spike proteins. Using SARS-COV-2 and SARS-CoV-1 lentivirus based pseudoviruses, we show that neutralizing antibody responses were predominantly SARS-CoV-2 specific. These data define patterns of cross-reactive binding and neutralizing serum responses induced by SARS-CoV-2 infection and vaccination in rhesus macaques. Our observations have important implications for understanding polyclonal responses to SARS-CoV-2 Spike, which will facilitate future CoV vaccine assessment and development. Importance The rapid development and deployment of SARS-CoV-2 vaccines has been unprecedented. In this study, we explore the cross-reactivity of SARS-CoV-2 specific antibody responses to other coronaviruses. By analyzing responses from NHPs both before and after immunization with DNA or Ad26 vectored vaccines, we find patterns of cross reactivity that mirror those induced by SARS-CoV-2 infection. These data highlight the similarities between infection and vaccine induced humoral immunity for SARS-CoV-2 and cross-reactivity of these responses to other CoVs.

scholarly journals SARS-CoV-2 Neutralizing Antibody Responses towards Full-Length Spike Protein and the Receptor-Binding Domain

2021 ◽  
pp. ji2100272
Author(s):  
Rafael Bayarri-Olmos ◽  
Manja Idorn ◽  
Anne Rosbjerg ◽  
Laura Pérez-Alós ◽  
Cecilie Bo Hansen ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Antibody Responses ◽  
Full Length ◽  
Spike Protein ◽  
Receptor Binding Domain

scholarly journals Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality

2020 ◽  
Author(s):  
William Morgenlander ◽  
Stephanie Henson ◽  
Daniel Monaco ◽  
Athena Chen ◽  
Kirsten Littlefield ◽  
...  
Keyword(s):  
Polyclonal Antibody ◽  
Strong Correlation ◽  
Neutralizing Antibodies ◽  
High Titer ◽  
Fusion Peptide ◽  
Cross Reactivity ◽  
Antibody Responses ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Human Coronavirus

AbstractCOVID-19 convalescent plasma, particularly plasma with high-titer SARS-CoV-2 (CoV2) antibodies, has been successfully used for treatment of COVID-19. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the four endemic human coronavirus (HCoV) genomes in 126 COVID-19 convalescent plasma donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies to SARS-CoV-2. We also found that plasma preferentially reactive to the CoV2 receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a two-peptide serosignature that identifies plasma donations with high anti-S titer but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting therapeutic plasma with desired functionalities.

scholarly journals An Antigenic Space Framework for Understanding Antibody Escape of SARS-CoV-2 Variants

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2009
Author(s):  
Nathaniel L. Miller ◽  
Thomas Clark ◽  
Rahul Raman ◽  
Ram Sasisekharan
Keyword(s):  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Host Immunity ◽  
Residue Level ◽  
Antibody Responses ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Antigenic Sites

The evolution of mutations in SARS-CoV-2 at antigenic sites that impact neutralizing antibody responses in humans poses a risk to immunity developed through vaccination and natural infection. The highly successful RNA-based vaccines have enabled rapid vaccine updates that incorporate mutations from current variants of concern (VOCs). It is therefore important to anticipate future antigenic mutations as the virus navigates the heterogeneous global landscape of host immunity. Toward this goal, we survey epitope-paratope interfaces of anti-SARS-CoV-2 antibodies to map an antigenic space that captures the role of each spike protein residue within the polyclonal antibody response directed against the ACE2-receptor binding domain (RBD) or the N-terminal domain (NTD). In particular, the antigenic space map builds on recently published epitope definitions by annotating epitope overlap and orthogonality at the residue level. We employ the antigenic space map as a framework to understand how mutations on nine major variants contribute to each variant’s evasion of neutralizing antibodies. Further, we identify constellations of mutations that span the orthogonal epitope regions of the RBD and NTD on the variants with the greatest antibody escape. Finally, we apply the antigenic space map to predict which regions of antigenic space—should they mutate—may be most likely to complementarily augment antibody evasion for the most evasive and transmissible VOCs.

Sign in / Sign up

Export Citation Format

Share Document