scholarly journals Modified Vaccinia Ankara Based SARS-CoV-2 Vaccine Expressing Full-Length Spike Induces Strong Neutralizing Antibody Response

2020 ◽  
Author(s):  
Nanda Kishore Routhu ◽  
Sailaja Gangadhara ◽  
Narayanaiah Cheedarla ◽  
Ayalnesh Shiferaw ◽  
Sheikh Abdul Rahman ◽  
...  
Keyword(s):  
Antibody Response ◽  
Room Temperature ◽  
Vaccine Candidate ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Full Length ◽  
Spike Protein ◽  
Strongly Correlated ◽  
Igg Antibodies ◽  
Potential Vaccine

AbstractThere is a great need for the development of vaccines for preventing SARS-CoV-2 infection and mitigating the COVID-19 pandemic. Here, we developed two modified vaccinia Ankara (MVA) based vaccines which express either a membrane anchored full-length spike protein (MVA/S) stabilized in a prefusion state or the S1 region of the spike (MVA/S1) which forms trimers and is secreted. Both immunogens contained the receptor-binding domain (RBD) which is a known target of antibody-mediated neutralization. Following immunizations with MVA/S or MVA/S1, both spike protein recombinants induced strong IgG antibodies to purified full-length SARS-CoV-2 spike protein. The MVA/S induced a robust antibody response to purified RBD, S1 and S2 whereas MVA/S1 induced an antibody response to the S1 region outside of the RBD region. Both vaccines induced an antibody response in the lung and that was associated with induction of bronchus-associated lymphoid tissue. MVA/S but not MVA/S1 vaccinated mice generated robust neutralizing antibody responses against SARS-CoV-2 that strongly correlated with RBD antibody binding titers. Mechanistically, S1 binding to ACE-2 was strong but reduced following prolonged pre-incubation at room temperature suggesting confirmation changes in RBD with time. These results demonstrate MVA/S is a potential vaccine candidate against SARS-CoV-2 infection.

scholarly journals Potent anti-SARS-CoV-2 Antibody Responses are Associated with Better Prognosis in Hospital Inpatient COVID-19 Disease

2020 ◽  
Author(s):  
Patrick J Tighe ◽  
Richard A Urbanowicz ◽  
Lucy Fairclough ◽  
C Patrick McClure ◽  
Brian J Thomson ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Clinical Intervention ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Effective Vaccine ◽  
Hospital Inpatient ◽  
Protein Variant ◽  
Immune Correlates

COVID-19 continues to cause a pandemic, having infected more than 20 million people globally. Successful elimination of the SARS-CoV-2 virus will require an effective vaccine. However, the immune correlates of infection are currently poorly understood. While neutralizing antibodies are believed to be essential for protection against infection, the contribution of the neutralizing antibody response to resolution of SARS-CoV-2 infection has not yet been defined. In this study the antibody responses to the SARS-CoV-2 spike protein and nucleocapsid proteins were investigated in a UK patient cohort, using optimised immunoassays and a retrovirus-based pseudotype entry assay. It was discovered that in severe COVID-19 infections an early antibody response to both antigens was associated with improved prognosis of infection. While not all SARS-CoV-2-reactive sera were found to possess neutralizing antibodies, neutralizing potency of sera was found to be greater in patients who went on to resolve infection, compared with those that died from COVID-19. Furthermore, viral genetic variation in spike protein was found to influence the production of neutralizing antibodies. Infection with the recently described spike protein variant 614G produced higher levels of neutralizing antibodies when compared to viruses possessing the 614D variant. These findings support the assertion that vaccines targeting generation of neutralizing antibodies may be useful at limiting SARS-CoV-2 infection. Assessment of the antibody responses to SARS-CoV-2 at time of diagnosis will be a useful addition to the diagnostic toolkit, enabling stratification of clinical intervention for severe COVID-19 disease.

scholarly journals Dominant Epitopes of the C6 Diagnostic Peptide of Borrelia burgdorferi Are Largely Inaccessible to Antibody on the Parent VlsE Molecule

2007 ◽  
Vol 14 (8) ◽  
pp. 931-936 ◽  
Author(s):  
Monica E. Embers ◽  
Mary B. Jacobs ◽  
Barbara J. B. Johnson ◽  
Mario T. Philipp
Keyword(s):  
Antibody Response ◽  
Variable Region ◽  
Immunoglobulin M ◽  
Antibody Responses ◽  
Full Length ◽  
Molecular Surface ◽  
Surface Molecule ◽  
Igg Antibodies ◽  
Specific Antibodies ◽  
Variable Surface

ABSTRACTLyme borreliosis (LB) is a disease for which antibody-based detection assays are often required for diagnosis. The variable surface molecule VlsE and IR6, one of its invariable regions, are commonly targeted by the antibody response in infected individuals. A series of enzyme-linked immunosorbent assays was performed to comparatively examine the antibody responses of North American LB patients (n= 37) to VlsE and invariable segments of this molecule. Both immunoglobulin M (IgM) and IgG responses to full-length VlsE and to peptides reproducing invariable regions 2, 4, and 6, as well as the invariable domains at the amino and carboxyl termini of VlsE, were assessed. The proportions and specificities of reactivity to the invariable segments were tested by using cognate peptides as competitors for VlsE binding by patient serum antibodies. IR6 epitopes (by the C6 peptide) were found to dominate the response to invariable segments. IR6 (C6)-specific antibodies were detected in 78% of the serum specimens, whereas <40% of patients generated antibodies that bound the N- or C-terminal domain and <12% of patients responded to either IR2 or IR4. Interestingly, 15 of 37 patients generated IgG antibodies that reacted with C6 but not with VlsE. Conversely, IgM responses were frequent for VlsE but not for invariable segments. A representative number of the serum specimens (n= 8) that contained IgG antibodies reacting with both C6 and VlsE was assessed in competition experiments, using C6 as a competitor. Only half of these specimens contained IgG antibodies whose binding to VlsE could be inhibited >50% by competition with the added C6 peptide. The median percent inhibition was 45.5%. These findings indicate that IR6 epitopes are largely concealed from the VlsE molecular surface and that full-length VlsE-based diagnosis likely detects antibodies to conformational and/or variable region epitopes.

scholarly journals CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease Following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1346
Author(s):  
Jennifer K. DeMarco ◽  
Joshua M. Royal ◽  
William E. Severson ◽  
Jon D. Gabbard ◽  
Steve Hume ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Potential Role ◽  
Vaccine Candidate ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Symptomatic Disease ◽  
Human Igg1

We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2–8 or 22–28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18-hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus-associated mortality and symptomatic disease. Our data indicated that a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS-CoV-2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is characteristic of severe cases of COVID-19.

scholarly journals Robust neutralizing antibodies to SARS-CoV-2 infection persist for months

Science ◽  
2020 ◽  
Vol 370 (6521) ◽  
pp. 1227-1230 ◽  
Author(s):  
Ania Wajnberg ◽  
Fatima Amanat ◽  
Adolfo Firpo ◽  
Deena R. Altman ◽  
Mark J. Bailey ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
York City ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Global Pandemic

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with millions infected and more than 1 million fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here, on the basis of a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City, we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust immunoglobulin G antibody responses against the viral spike protein. We also show that titers are relatively stable for at least a period of about 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggest that more than 90% of seroconverters make detectable neutralizing antibody responses. These titers remain relatively stable for several months after infection.

scholarly journals Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in patients with COVID-19

2020 ◽  
Vol 5 (52) ◽  
pp. eabe5511
Author(s):  
Baweleta Isho ◽  
Kento T. Abe ◽  
Michelle Zuo ◽  
Alainna J. Jamal ◽  
Bhavisha Rathod ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Receptor Binding ◽  
Antibody Responses ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Surrogate Measure ◽  
Antibody Levels ◽  
Negative Controls

Although the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) immunoglobulin G (IgG), IgA, and IgM responses to the SARS-CoV-2 spike protein (full-length trimer) and its receptor binding domain (RBD) in serum and saliva of acute and convalescent patients with laboratory-diagnosed coronavirus disease 2019 (COVID-19) ranging from 3 to 115 days postsymptom onset (PSO), compared with negative controls. Anti–SARS-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16 to 30 days PSO. Longitudinal analysis revealed that anti–SARS-CoV-2 IgA and IgM antibodies rapidly decayed, whereas IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. Last, IgG, IgM, and, to a lesser extent, IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that serum and saliva IgG antibodies to SARS-CoV-2 are maintained in most of the patients with COVID-19 for at least 3 months PSO. IgG responses in saliva may serve as a surrogate measure of systemic immunity to SARS-CoV-2 based on their correlation with serum IgG responses.

scholarly journals Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population

2020 ◽  
Author(s):  
Sabra L. Klein ◽  
Andrew Pekosz ◽  
Han-Sol Park ◽  
Rebecca L. Ursin ◽  
Janna R. Shapiro ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Antibody Responses ◽  
Full Length ◽  
Neutralization Titer ◽  
Humoral Immune ◽  
Virus Neutralization Assay ◽  
Male Sex ◽  
Substantial Heterogeneity

AbstractConvalescent plasma is currently one of the leading treatments for COVID-19, but there is a paucity of data identifying therapeutic efficacy. A comprehensive analysis of the antibody responses in potential plasma donors and an understanding of the clinical and demographic factors that drive variant antibody responses is needed. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated by a SARS-CoV-2 virus neutralization assay using Vero-E6-TMPRSS2 cells, commercial IgG and IgA ELISA to Spike (S) protein S1 domain (Euroimmun), IgA, IgG and IgM indirect ELISAs to the full-length S or S-receptor binding domain (S-RBD), and an IgG avidity assay. Multiple linear regression and predictive models were utilized to assess the correlations between antibody responses with demographic and clinical characteristics. IgG titers were greater than either IgM or IgA for S1, full length S, and S-RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing titers. Using neutralization titer as the reference, the sensitivity of the IgG ELISAs ranged between 95-98%, but specificity was only 20-32%. Male sex, older age, and hospitalization with COVID-19 were all consistently associated with increased antibody responses across the serological assays. Neutralizing antibody titers were reduced over time in contrast to overall antibody responses. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody levels.One Sentence SummaryThere is substantial heterogeneity in the antibody response to SARS-CoV-2 infection, with greater antibody responses being associated with male sex, advancing age, and hospitalization with COVID-19.

scholarly journals Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses

2022 ◽  
Author(s):  
Benjamin L. Sievers ◽  
Saborni Chakraborty ◽  
Yong Xue ◽  
Terri Gelbart ◽  
Joseph C. Gonzalez ◽  
...  
Keyword(s):  
Antibody Response ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Vaccine Responses ◽  
Viral Antigens ◽  
Vesicular Stomatitis ◽  
Substantial Heterogeneity ◽  
Over Time

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that possess mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.1.529) spike protein appear to diminish the protection conferred by pre-existing immunity. Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses whereas responses may have been reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.

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 SARS-CoV-2 infection induces robust, neutralizing antibody responses that are stable for at least three months

2020 ◽  
Author(s):  
Ania Wajnberg ◽  
Fatima Amanat ◽  
Adolfo Firpo ◽  
Deena Altman ◽  
Mark Bailey ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
Antibody Response ◽  
York City ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Igg Antibody ◽  
Global Pandemic ◽  
Near Term

SARS-CoV-2 has caused a global pandemic with millions infected and numerous fatalities. Questions regarding the robustness, functionality and longevity of the antibody response to the virus remain unanswered. Here we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust IgG antibody responses against the viral spike protein, based on a dataset of 19,860 individuals screened at Mount Sinai Health System in New York City. We also show that titers are stable for at least a period approximating three months, and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggests that more than 90% of seroconverters make detectible neutralizing antibody responses and that these titers are stable for at least the near-term future.

scholarly journals Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

2021 ◽  
Vol 7 (22) ◽  
pp. eabg7156
Author(s):  
So-Hee Hong ◽  
Hanseul Oh ◽  
Yong Wook Park ◽  
Hye Won Kwak ◽  
Eun Young Oh ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
Statistical Significance ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Vaccine Candidates ◽  
Cell Responses ◽  
Antibody Levels ◽  
Further Development

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

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