scholarly journals Immunogenicity of convalescent and vaccinated sera against clinical isolates of ancestral SARS-CoV-2, beta, delta, and omicron variants

2022 ◽  
Author(s):  
Arinjay Banerjee ◽  
Jocelyne Lew ◽  
Andrea Kroeker ◽  
Kaushal Baid ◽  
Patryk Aftanas ◽  
...  
Keyword(s):  
Clinical Specimen ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Clinical Isolates ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Vaccination Strategies ◽  
Antibody Titers ◽  
Ancestral Virus ◽  
Antibody Levels

The omicron variant of concern (VOC) of SARS-CoV-2 was first reported in November 2021 in Botswana and South Africa. Omicron variant has evolved multiple mutations within the spike protein and the receptor binding domain (RBD), raising concerns of increased antibody evasion. Here, we isolated infectious omicron from a clinical specimen obtained in Canada. The neutralizing activity of sera from 65 coronavirus disease (COVID-19) vaccine recipients and convalescent individuals against clinical isolates of ancestral SARS-CoV-2, beta, delta, and omicron VOCs was assessed. Convalescent sera from unvaccinated individuals infected by the ancestral virus during the first wave of COVID-19 in Canada (July, 2020) demonstrated reduced neutralization against beta, delta and omicron VOCs. Convalescent sera from unvaccinated individuals infected by the delta variant (May-June, 2021) neutralized omicron to significantly lower levels compared to the delta variant. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of both delta and omicron variants relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Importantly, infection alone, either with ancestral SARS-CoV-2 or the delta variant was not sufficient to induce high neutralizing antibody titers against omicron. This data will inform current booster vaccination strategies and we highlight the need for additional studies to identify longevity of immunity against SARS-CoV-2 and optimal neutralizing antibody levels that are necessary to prevent infection and/or severe COVID-19.

scholarly journals Reduced binding and neutralization of infection- and vaccine-induced antibodies to the B.1.351 (South African) SARS-CoV-2 variant

2021 ◽  
Author(s):  
Venkata Viswanadh Edara ◽  
Carson Norwood ◽  
Katharine Floyd ◽  
Lilin Lai ◽  
Meredith E. Davis-Gardner ◽  
...  
Keyword(s):  
South African ◽  
Receptor Binding ◽  
Symptom Onset ◽  
Protective Immunity ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Live Virus ◽  
Fold Reduction ◽  
Antibody Titers

SUMMARYThe emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies to neutralize these variants. We compared antibody binding and live virus neutralization of sera from naturally infected and spike mRNA vaccinated individuals against a circulating SARS-CoV-2 B.1 variant and the emerging B.1.351 variant. In acutely-infected (5-19 days post-symptom onset), convalescent COVID-19 individuals (through 8 months post-symptom onset) and mRNA-1273 vaccinated individuals (day 14 post-second dose), we observed an average 4.3-fold reduction in antibody titers to the B.1.351-derived receptor binding domain of the spike protein and an average 3.5-fold reduction in neutralizing antibody titers to the SARS-CoV-2 B.1.351 variant as compared to the B.1 variant (spike D614G). However, most acute and convalescent sera from infected and all vaccinated individuals neutralize the SARS-CoV-2 B.1.351 variant, suggesting that protective immunity is retained against COVID-19.

scholarly journals Emergency Response for Evaluating SARS-CoV-2 Immune Status, Seroprevalence and Convalescent Plasma in Argentina

2020 ◽  
Author(s):  
Diego S. Ojeda ◽  
María Mora Gonzalez Lopez Ledesma ◽  
Horacio Pallares ◽  
Guadalupe S. Costa Navarro ◽  
Lautaro Sanchez ◽  
...  
Keyword(s):  
Health Care ◽  
Immune Responses ◽  
Health Care Workers ◽  
Antibody Responses ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Care Workers ◽  
Antibody Titers ◽  
Health Institutions ◽  
Antibody Levels

ABSTRACTWe report the emergency development and application of a robust serologic test to evaluate acute and convalescent antibody responses to SARS-CoV-2 in Argentina. The assays, COVIDAR IgG and IgM, which were produced and provided for free to health authorities, private and public health institutions and nursing homes, use a combination of a trimer stabilized spike protein and the receptor binding domain (RBD) in a single enzyme-linked immunosorbent assay (ELISA) plate. Over half million tests have already been distributed to detect and quantify antibodies for multiple purposes, including assessment of immune responses in hospitalized patients and large seroprevalence studies in neighborhoods, slums and health care workers, which resulted in a powerful tool for asymptomatic detection and policy making in the country. Analysis of antibody levels and longitudinal studies of symptomatic and asymptomatic SARS-CoV-2 infections in over one thousand patient samples provided insightful information about IgM and IgG seroconversion time and kinetics, and IgM waning profiles. At least 35% of patients showed seroconversion within 7 days, and 95% within 45 days of symptoms onset, with simultaneous or close sequential IgM and IgG detection. Longitudinal studies of asymptomatic cases showed a wide range of antibody responses with median levels below those observed in symptomatic patients. Regarding convalescent plasma applications, a protocol was standardized for the assessment of end point IgG antibody titers with COVIDAR with more than 500 plasma donors. The protocol showed a positive correlation with neutralizing antibody titers, and was used to assess antibody titers for clinical trials and therapies across the country. Here, we demonstrate the importance of providing a robust and specific serologic assay for generating new information about antibody kinetics in infected individuals and mitigation policies to cope with pandemic needs.AUTHOR SUMMARYThe development of robust and specific serologic assays to detect antibodies to SARS-CoV-2 is essential to understand the pandemic evolution and to stablish mitigation strategies. Here, we report the emergency development, production and application of a versatile ELISA test for detecting antibodies against the whole spike protein and its receptor binding domain. Over half million tests have been freely distributed in public and private health institutions of Argentina for evaluating immune responses, convalescent plasma programs and for large seroprevalence studies in neighborhoods and health care workers. We are still learning how and when to use serologic testing in different epidemiological settings. This program allowed us to produce large amount of high quality data on antibody levels in symptomatic and asymptomatic SARS-CoV-2 infections and generate relevant information about IgM and IgG seroconversion time and kinetics. We also present standardized protocols for antibody quantification as guidance for convalescent donor plasma selection in hospitals throughout the country for compassionate use and clinical trials. Here, we provide a framework for generating widely available tools, protocols and information of antibody responses for pandemic management.

scholarly journals Dynamics of neutralizing antibody titers in the months after SARS-CoV-2 infection

2020 ◽  
Author(s):  
Katharine HD Crawford ◽  
Adam S Dingens ◽  
Rachel Eguia ◽  
Caitlin R Wolf ◽  
Naomi Wilcox ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Early Immune Response ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Time Frames ◽  
Initial Peak

Most individuals infected with SARS-CoV-2 develop neutralizing antibodies that target the viral spike protein. Here we quantify how levels of these antibodies change in the months following SARS-CoV-2 infection by examining longitudinal samples collected between ≈30 and 152 days post-symptom onset from a prospective cohort of 34 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about four-fold from one to four months post-symptom onset. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B-cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.

scholarly journals Dynamics of Neutralizing Antibody Titers in the Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection

2020 ◽  
Author(s):  
Katharine H D Crawford ◽  
Adam S Dingens ◽  
Rachel Eguia ◽  
Caitlin R Wolf ◽  
Naomi Wilcox ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Time Frames ◽  
Initial Peak

Abstract Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop neutralizing antibodies that target the viral spike protein. In this study, we quantified how levels of these antibodies change in the months after SARS-CoV-2 infection by examining longitudinal samples collected approximately 30–152 days after symptom onset from a prospective cohort of 32 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about 4-fold from 1 to 4 months after symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike protein or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.

scholarly journals Longitudinal variation in SARS-CoV-2 antibody levels and emergence of viral variants: implications for the ability of serological assays to predict immunity.

2021 ◽  
Author(s):  
Frauke Muecksch ◽  
Helen Wise ◽  
Kate Templeton ◽  
Becky Batchelor ◽  
Maria Squires ◽  
...  
Keyword(s):  
High Throughput ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Serological Tests ◽  
Neutralization Activity ◽  
Neutralizing Activity ◽  
Quantitative Measurements ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Selection Of

Background Serological assays are being deployed to monitor antibody responses in SARS-CoV-2 convalescents and vaccine recipients. There is a need to determine whether such assays can predict immunity, as antibody levels wane and viral variants emerge. Methods We measured antibodies in a cohort of SARS-CoV-2 infected patients using several high-throughput serological tests and functional neutralization assays. The effects of time and spike protein sequence variation on the performance and predictive value of the various assays was assessed. Findings Neutralizing antibody titers decreased over the first few months post-infection but stabilized thereafter, at about 30% of the level observed shortly after infection. Serological assays commonly used to measure antibodies against SARS-CoV-2 displayed a range of sensitivities that declined to varying extents over time. Quantitative measurements generated by serological assays based on the spike protein were better at predicting neutralizing antibody titers than assays based on nucleocapsid, but performance was variable and manufacturer positivity thresholds were not able to predict the presence or absence of detectable neutralizing activity. Even though there was some deterioration in correlation between serological measurements and functional neutralization activity, some assays maintained an ability to predict neutralizing titers, even against variants of concern. Interpretation The ability of high throughput serological assays to predict neutralizing antibody titers is likely crucial for evaluation of immunity at the population scale. These data will facilitate the selection of the most suitable assays as surrogates of functional neutralizing activity and suggest that such measurements may have utility in clinical practice.

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 Exposures to different SARS-CoV-2 spike variants elicit neutralizing antibody responses with differential specificity towards established and emerging strains

2021 ◽  
Author(s):  
Matthew T Laurie ◽  
Jamin Liu ◽  
Sara Sunshine ◽  
James Peng ◽  
Douglas Black ◽  
...  
Keyword(s):  
Immune Response ◽  
Wide Spectrum ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Vaccination Strategies ◽  
Cross Neutralization ◽  
The Relationship

The wide spectrum of SARS-CoV-2 variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of the immune response to different spike protein versions. Here, we compare the neutralization of variants of concern, including B.1.617.2 (Delta) in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing one or more spike mutations with the immunizing exposure. We also observe that exposure to multiple spike variants increases the breadth of variant cross-neutralization. These findings contribute to understanding the relationship between exposures and antibody responses and may inform booster vaccination strategies.

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.

scholarly journals Towards Quantitative and Standardized Serological and Neutralization Assays for COVID-19

2021 ◽  
Vol 22 (5) ◽  
pp. 2723
Author(s):  
Linhua Tian ◽  
Elzafir B. Elsheikh ◽  
Paul N. Patrone ◽  
Anthony J. Kearsley ◽  
Adolfas K. Gaigalas ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Epidemiologic Studies ◽  
Cross Reactivity ◽  
Receptor Binding Domain ◽  
Proof Of Concept ◽  
Reference Standard ◽  
Improve Measurement ◽  
Antibody Titers

Quantitative and robust serology assays are critical measurements underpinning global COVID-19 response to diagnostic, surveillance, and vaccine development. Here, we report a proof-of-concept approach for the development of quantitative, multiplexed flow cytometry-based serological and neutralization assays. The serology assays test the IgG and IgM against both the full-length spike antigens and the receptor binding domain (RBD) of the spike antigen. Benchmarking against an RBD-specific SARS-CoV IgG reference standard, the anti-SARS-CoV-2 RBD antibody titer was quantified in the range of 37.6 µg/mL to 31.0 ng/mL. The quantitative assays are highly specific with no correlative cross-reactivity with the spike proteins of MERS, SARS1, OC43 and HKU1 viruses. We further demonstrated good correlation between anti-RBD antibody titers and neutralizing antibody titers. The suite of serology and neutralization assays help to improve measurement confidence and are complementary and foundational for clinical and epidemiologic studies.

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