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 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 Variable loss of antibody potency against SARS-CoV-2 B.1.1.529 (Omicron)

2021 ◽  
Author(s):  
Daniel J. Sheward ◽  
Changil Kim ◽  
Roy A. Ehling ◽  
Alec Pankow ◽  
Xaquin Castro Dopico ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Blood Donors ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Antibody Responses ◽  
Pseudotyped Virus ◽  
Virus Neutralization Assay ◽  
Form Part ◽  
Antibody Titers ◽  
Cross Neutralization

The recently-emerged SARS-CoV-2 B.1.1.529 variant (Omicron) is spreading rapidly in many countries, with a spike that is highly diverged from the pandemic founder, raising fears that it may evade neutralizing antibody responses. We cloned the Omicron spike from a diagnostic sample which allowed us to rapidly establish an Omicron pseudotyped virus neutralization assay, sharing initial neutralization results only 13 days after the variant was first reported to the WHO, 8 days after receiving the sample. Here we show that Omicron is substantially resistant to neutralization by several monoclonal antibodies that form part of clinical cocktails. Further, we find neutralizing antibody responses in pooled reference sera sampled shortly after infection or vaccination are substantially less potent against Omicron, with neutralizing antibody titers reduced by up to 45 fold compared to those for the pandemic founder. Similarly, in a cohort of convalescent sera prior to vaccination, neutralization of Omicron was low to undetectable. However, in recent samples from two cohorts from Stockholm, Sweden, antibody responses capable of cross-neutralizing Omicron were prevalent. Sera from infected-then-vaccinated healthcare workers exhibited robust cross-neutralization of Omicron, with an average potency reduction of only 5-fold relative to the pandemic founder variant, and some donors showing no loss at all. A similar pattern was observed in randomly sampled recent blood donors, with an average 7-fold loss of potency. Both cohorts showed substantial between-donor heterogeneity in their ability to neutralize Omicron. Together, these data highlight the extensive but incomplete evasion of neutralizing antibody responses by the Omicron variant, and suggest that increasing the magnitude of neutralizing antibody responses by boosting with unmodified vaccines may suffice to raise titers to levels that are protective.

scholarly journals Antibody Response of BNT162b2 and CoronaVac Platforms in Recovered Individuals Previously Infected by COVID-19 against SARS-CoV-2 Wild Type and Delta Variant

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1442
Author(s):  
Ruiqi Zhang ◽  
Ka-Wa Khong ◽  
Ka-Yi Leung ◽  
Danlei Liu ◽  
Yujing Fan ◽  
...  
Keyword(s):  
Antibody Response ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Fold Increase ◽  
Neutralization Assay ◽  
Wild Type ◽  
Vaccine Platform ◽  
Live Virus ◽  
Virus Neutralization Assay ◽  
Geometric Mean Titre

Vaccinating recovered patients previously infected by COVID-19 with mRNA vaccines to boost their immune response against wild-type viruses (WT), we aimed to investigate whether vaccine platform and time of vaccination affect immunogenicity against the SARS-CoV-2 WT and Delta variant (DV). Convalescent patients infected by COVID-19 were recruited and received one booster dose of the BNT162b2 (PC-B) or CoronaVac (PC-C) vaccines, while SARS-CoV-2 naïve subjects received two doses of the BNT162b2 (CN-B) or CoronaVac (CN-C) vaccines. The neutralizing antibody in sera against the WT and DV was determined with live virus neutralization assay (vMN). The vMN geometric mean titre (GMT) against WT in recovered individuals previously infected by COVID-19 reduced significantly from 60.0 (95% confidence interval (CI), 46.5–77.4) to 33.9 (95% CI, 26.3–43.7) at 6 months post recovery. In the PC-B group, the BNT162b2 vaccine enhanced antibody response against WT and DV, with 22.3-fold and 20.4-fold increases, respectively. The PC-C group also showed 1.8-fold and 2.2-fold increases for WT and DV, respectively, after receiving the CoronaVac vaccine. There was a 10.6-fold increase in GMT in the CN-B group and a 1.3-fold increase in the CN-C group against DV after full vaccination. In both the PC-B and PC-C groups, there was no difference between GMT against WT and DV after vaccination. Subjects in the CN-B and CN-C groups showed inferior GMT against DV compared with GMT against WT after vaccination. In this study, one booster shot effectively enhanced the pre-existing neutralizing activity against WT and DV in recovered subjects.

scholarly journals Magnitude and breadth of neutralizing antibody responses elicited by SARS-CoV-2 infection or vaccination

2022 ◽  
Author(s):  
Benjamin L. Sievers ◽  
Saborni Chakraborty ◽  
Yong Xue ◽  
Terri Gelbart ◽  
Joseph C. Gonzalez ◽  
...  
Keyword(s):  
Antibody Response ◽  
Pregnant Women ◽  
Neutralizing Antibody ◽  
Healthy Adults ◽  
Antibody Responses ◽  
Vaccine Responses ◽  
Viral Antigens ◽  
Substantial Heterogeneity ◽  
Over Time

Multiple SARS-CoV-2 variants that possess mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. While the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.529) spike appear to diminish the efficacy of pre-existing immunity. Using pseudoparticles expressing the spike of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in naturally infected and in mRNA-vaccinated individuals. We observed that while boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta and Omicron variants, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses while responses were relatively 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 mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant

2021 ◽  
Author(s):  
Venkata-Viswanadh Edara ◽  
Kelly E Manning ◽  
Madison Ellis ◽  
Lilin Lai ◽  
Kathryn M Moore ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Antibody Responses ◽  
Spike Protein ◽  
Live Virus ◽  
Neutralizing Activity ◽  
Virus Neutralization Assay ◽  
Fold Reduction

The BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines generate potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the global emergence of SARS-CoV-2 variants with mutations in the spike protein, the principal antigenic target of these vaccines, has raised concerns over the neutralizing activity of vaccine-induced antibody responses. The Omicron variant, which emerged in November 2021, consists of over 30 mutations within the spike protein. Here, we used an authentic live virus neutralization assay to examine the neutralizing activity of the SARS-CoV-2 Omicron variant against mRNA vaccine-induced antibody responses. Following the 2nd dose, we observed a 30-fold reduction in neutralizing activity against the omicron variant. Through six months after the 2nd dose, none of the sera from naive vaccinated subjects showed neutralizing activity against the Omicron variant. In contrast, recovered vaccinated individuals showed a 22-fold reduction with more than half of the subjects retaining neutralizing antibody responses. Following a booster shot (3rd dose), we observed a 14-fold reduction in neutralizing activity against the omicron variant and over 90% of boosted subjects showed neutralizing activity against the omicron variant. These findings show that a 3rd dose is required to provide robust neutralizing antibody responses against the Omicron variant.

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 Viral Replicative Capacity, Antigen Availability via Hematogenous Spread, and High TFH:TFRRatios Drive Induction of Potent Neutralizing Antibody Responses

2019 ◽  
Vol 93 (6) ◽  
Author(s):  
Preethi Eldi ◽  
Geeta Chaudhri ◽  
Stephen L. Nutt ◽  
Timothy P. Newsome ◽  
Gunasegaran Karupiah
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Germinal Center ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Replicative Capacity ◽  
Hematogenous Spread ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Early Predictor

ABSTRACTLive viral vaccines elicit protective, long-lived humoral immunity, but the underlying mechanisms through which this occurs are not fully elucidated. Generation of affinity matured, long-lived protective antibody responses involve close interactions between T follicular helper (TFH) cells, germinal center (GC) B cells, and T follicular regulatory (TFR) cells. We postulated that escalating concentrations of antigens from replicating viruses or live vaccines, spread through the hematogenous route, are essential for the induction and maintenance of long-lived protective antibody responses. Using replicating and poorly replicating or nonreplicating orthopox and influenza A viruses, we show that the magnitude of TFH cell, GC B cell, and neutralizing antibody responses is directly related to virus replicative capacity. Further, we have identified that both lymphoid and circulating TFH:TFRcell ratios during the peak GC response can be used as an early predictor of protective, long-lived antibody response induction. Finally, administration of poorly or nonreplicating viruses to allow hematogenous spread generates significantly stronger TFH:TFRratios and robust TFH, GC B cell and neutralizing antibody responses.IMPORTANCENeutralizing antibody response is the best-known correlate of long-term protective immunity for most of the currently licensed clinically effective viral vaccines. However, the host immune and viral factors that are critical for the induction of robust and durable antiviral humoral immune responses are not well understood. Our study provides insight into the dynamics of key cellular mediators of germinal center reaction during live virus infections and the influence of viral replicative capacity on the magnitude of antiviral antibody response and effector function. The significance of our study lies in two key findings. First, the systemic spread of even poorly replicating or nonreplicating viruses to mimic the spread of antigens from replicating viruses due to escalating antigen concentration is fundamental to the induction of durable antibody responses. Second, the TFH:TFRratio may be used as an early predictor of protective antiviral humoral immune responses long before memory responses are generated.

scholarly journals Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant

2021 ◽  
Author(s):  
Venkata Viswanadh Edara ◽  
Katharine Floyd ◽  
Lilin Lai ◽  
Meredith Gardner ◽  
William Hudson ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Antibody Responses ◽  
Live Virus ◽  
Virus Neutralization Assay ◽  
Recent Emergence ◽  
The Uk ◽  
Induced Immunity

AbstractAntibody responses against the SARS-CoV-2 Spike protein correlate with protection against COVID-19. Serum neutralizing antibodies appear early after symptom onset following SARS-CoV-2 infection and can last for several months. Similarly, the messenger RNA vaccine, mRNA-1273, generates serum neutralizing antibodies that are detected through at least day 119. However, the recent emergence of the B.1.1.7 variant has raised significant concerns about the breadth of these neutralizing antibody responses. In this study, we used a live virus neutralization assay to compare the neutralization potency of sera from infected and vaccinated individuals against a panel of SARS-CoV-2 variants, including SARS-CoV-2 B.1.1.7. We found that both infection- and vaccine-induced antibodies were effective at neutralizing the SARS-CoV-2 B.1.1.7 variant. These findings support the notion that in the context of the UK variant, vaccine-induced immunity can provide protection against COVID-19. As additional SARS-CoV-2 viral variants continue to emerge, it is crucial to monitor their impact on neutralizing antibody responses following infection and vaccination.

scholarly journals Antibody responses in buffalos immunized with Clostridium perfringens beta and epsilon toxoids

2001 ◽  
Vol 46 (No. 9–10) ◽  
pp. 241-243 ◽  
Author(s):  
S. Rahman M ◽  
K. Baek B ◽  
T. Hong S ◽  
H. Lee J
Keyword(s):  
Antibody Titre ◽  
Clostridium Perfringens ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Control Group ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Antibody Titres ◽  
Group A ◽  
And Control

The antibody responses to toxoids were measured to investigate whether Clostridium perfringens beta and epsilon toxoids induced protective humoral immune responses in buffalos. Total of 24 buffalos were divided into 4 groups (n = 6), beta toxoid, epsilon toxoid, combination and control groups. These buffalo groups were administered each of the designated toxoids. Immunizations in the beta and epsilon toxoid groups induced strong antibody responses. The neutralizing antibody titres from the beta and epsilon toxoid groups were equally log101.2 on day 21 after inoculation whereas there was no antibody titre detected from the control group. A statistically significant (P < 0.01) increase in antibody titre was observed from day 0 to day 14 and 21 after inoculation. The antibody production did not vary significantly due to day of inoculation and toxoid interactions.

scholarly journals Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 284
Author(s):  
Hulda R. Jonsdottir ◽  
Michel Bielecki ◽  
Denise Siegrist ◽  
Thomas W. Buehrer ◽  
Roland Züst ◽  
...  
Keyword(s):  
Young Adults ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Asymptomatic Infection ◽  
Homogeneous Population ◽  
Humoral Immune ◽  
Antibody Titers

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

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