scholarly journals Declining Levels of Neutralizing Antibodies Against SARS-CoV-2 in Convalescent COVID-19 Patients One Year Post Symptom Onset

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiandan Xiang ◽  
Boyun Liang ◽  
Yaohui Fang ◽  
Sihong Lu ◽  
Sumeng Li ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Protein S ◽  
Igg Antibodies ◽  
Neutralizing Activity ◽  
Specific Igg ◽  
One Year ◽  
Kinetics Of

Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.

scholarly journals Clinical course impacts early kinetics and long-term magnitude and amplitude of SARS-CoV-2 neutralizing antibodies beyond one year after infection

2021 ◽  
Author(s):  
Edwards Pradenas ◽  
Benjamin Trinité ◽  
Víctor Urrea ◽  
Silvia Marfil ◽  
Ferran Tarrés-Freixas ◽  
...  
Keyword(s):  
B Cells ◽  
Neutralizing Antibodies ◽  
Primary Infection ◽  
Natural Infection ◽  
Optimal Strategies ◽  
Longitudinal Models ◽  
Neutralizing Activity ◽  
Cross Neutralization ◽  
One Year

Background: Understanding the determinants of long-term immune responses to SARS-CoV-2 and the concurrent impact of vaccination and emerging variants of concern will guide optimal strategies to achieve global protection against the COVID-19 pandemic. Methods: A prospective cohort of 332 COVID-19 patients was followed beyond one year. Plasma neutralizing activity was evaluated using HIV-based reporter pseudoviruses expressing different SARS-CoV-2 spikes and was longitudinally analyzed using mixed-effects models. Findings: Long-term neutralizing activity was stable beyond one year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short- and long-lived memory B cells, while outpatient responses were dominated by long-lived B cells. In both groups, vaccination boosted responses to natural infection, although viral variants, mainly B.1.351, reduced the efficacy of neutralization. Importantly, despite showing higher neutralization titers, hospitalized patients showed lower cross-neutralization of B.1.351 variant compared to outpatients. Multivariate analysis identified severity of primary infection as the factor that independently determines both the magnitude and the inferior cross-neutralization activity of long-term neutralizing responses. Conclusions: Neutralizing response induced by SARS-CoV-2 is heterogeneous in magnitude but stable beyond one year after infection. Vaccination boosts these long-lasting natural neutralizing responses, counteracting the significant resistance to neutralization of new viral variants. Severity of primary infection determines higher magnitude but poorer quality of long-term neutralizing responses.

scholarly journals Endogenously Produced SARS-CoV-2 Specific IgG Antibodies May Have a Limited Impact on Clearing Nasal Shedding of Virus during Primary Infection in Humans

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 516
Author(s):  
Shuyi Yang ◽  
Keith R. Jerome ◽  
Alexander L. Greninger ◽  
Joshua T. Schiffer ◽  
Ashish Goyal
Keyword(s):  
Production Rate ◽  
Neutralizing Antibodies ◽  
Primary Infection ◽  
Natural Infection ◽  
Viral Clearance ◽  
Clinical Severity ◽  
Igg Antibodies ◽  
Igm Antibodies ◽  
Specific Igg ◽  
Specific Igg Antibodies

While SARS-CoV-2 specific neutralizing antibodies have been developed for therapeutic purposes, the specific viral triggers that drive the generation of SARS-CoV-2 specific IgG and IgM antibodies remain only partially characterized. Moreover, it is unknown whether endogenously derived antibodies drive viral clearance that might result in mitigation of clinical severity during natural infection. We developed a series of non-linear mathematical models to investigate whether SARS-CoV-2 viral and antibody kinetics are coupled or governed by separate processes. Patients with severe disease had a higher production rate of IgG but not IgM antibodies. Maximal levels of both isotypes were governed by their production rate rather than different saturation levels between people. Our results suggest that an exponential surge in IgG levels occurs approximately 5–10 days after symptom onset with no requirement for continual antigenic stimulation. SARS-CoV-2 specific IgG antibodies appear to have limited to no effect on viral dynamics but may enhance viral clearance late during primary infection resulting from the binding effect of antibody to virus, rather than neutralization. In conclusion, SARS-CoV-2 specific IgG antibodies may play only a limited role in clearing infection from the nasal passages despite providing long-term immunity against infection following vaccination or prior infection.

scholarly journals SARS-CoV-2 antibodies remain detectable 12 months after infection and antibody magnitude is associated with age and COVID-19 severity

2021 ◽  
Author(s):  
Eric D. Laing ◽  
Nusrat J. Epsi ◽  
Stephanie A. Richard ◽  
Emily C. Samuels ◽  
Wei Wang ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Serum Samples ◽  
Military Hospitals ◽  
Igg Binding ◽  
One Year

ABSTRACTImportanceThe persistence of SARS-CoV-2 antibodies may be a predictive correlate of protection for both natural infections and vaccinations. Identifying predictors of robust antibody responses is important to evaluate the risk of re-infection / vaccine failure and may be translatable to vaccine effectiveness.ObjectiveTo 1) determine the durability of anti-SARS-CoV-2 IgG and neutralizing antibodies in subjects who experienced mild and moderate to severe COVID-19, and 2) to evaluate the correlation of age and IgG responses to both endemic human seasonal coronaviruses (HCoVs) and SARS-CoV-2 according to infection outcome.DesignLongitudinal serum samples were collected from PCR-confirmed SARS-CoV-2 positive participants (U.S. active duty service members, dependents and military retirees, including a range of ages and demographics) who sought medical treatment at seven U.S. military hospitals from March 2020 to March 2021 and enrolled in a prospective observational cohort study.ResultsWe observed SARS-CoV-2 seropositivity in 100% of inpatients followed for six months (58/58) to one year (8/8), while we observed seroreversion in 5% (9/192) of outpatients six to ten months after symptom onset, and 18% (2/11) of outpatients followed for one year. Both outpatient and inpatient anti-SARS-CoV-2 binding-IgG responses had a half-life (T1/2) of >1000 days post-symptom onset. The magnitude of neutralizing antibodies (geometric mean titer, inpatients: 378 [246-580, 95% CI] versus outpatients: 83 [59-116, 95% CI]) and durability (inpatients: 65 [43-98, 95% CI] versus outpatients: 33 [26-40, 95% CI]) were associated with COVID-19 severity. Older age was a positive correlate with both higher IgG binding and neutralizing antibody levels when controlling for COVID-19 hospitalization status. We found no significant relationships between HCoV antibody responses and COVID-19 clinical outcomes, or the development of SARS-CoV-2 neutralizing antibodies.Conclusions and RelevanceThis study demonstrates that humoral responses to SARS-CoV-2 infection are robust on longer time-scales, including those arising from milder infections.However, the magnitude and durability of the antibody response after natural infection was lower and more variable in younger participants who did not require hospitalization for COVID-19. These findings support vaccination against SARS-CoV-2 in all suitable populations including those individuals that have recovered from natural infection.

scholarly journals Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders

2020 ◽  
Author(s):  
Emelie Marklund ◽  
Susannah Leach ◽  
Hannes Axelsson ◽  
Kristina Nordström ◽  
Heléne Norder ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Infection Prevalence ◽  
Igg Antibodies ◽  
Domain Specific ◽  
Serum Igg ◽  
Protein Receptor ◽  
Antibody Titers ◽  
Specific Igg ◽  
True Infection

Background: To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset. Results: Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P=0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset. Conclusions: Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys and for estimating the true infection prevalence in populations.

scholarly journals Kinetics of SARS-CoV-2 Specific and Neutralizing Antibodies over Seven Months after Symptom Onset in COVID-19 Patients

2021 ◽  
Author(s):  
Liguo Zhu ◽  
Xin Xu ◽  
Baoli Zhu ◽  
Xiling Guo ◽  
Ke Xu ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Kinetics Of ◽  
Forward Looking

The long-term characteristics of anti-SARS-CoV-2 antibodies among COVID-19 patients remain largely unclear. Tracking the longevity of these antibodies can provide a forward-looking reference for monitoring COVID-19.

scholarly journals Broadly Neutralizing Hemagglutinin Stalk-Specific Antibodies Induce Potent Phagocytosis of Immune Complexes by Neutrophils in an Fc-Dependent Manner

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Caitlin E. Mullarkey ◽  
Mark J. Bailey ◽  
Diana A. Golubeva ◽  
Gene S. Tan ◽  
Raffael Nachbagauer ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Fc Receptor ◽  
Igg Antibodies ◽  
Specific Antibodies ◽  
Effector Functions ◽  
Iga Antibodies ◽  
Specific Igg ◽  
Optimal Protection ◽  
Specific Igg Antibodies

ABSTRACTBroadly neutralizing antibodies that recognize the conserved hemagglutinin (HA) stalk have emerged as exciting new biotherapeutic tools to combat seasonal and pandemic influenza viruses. Our general understanding of the mechanisms by which stalk-specific antibodies achieve protection is rapidly evolving. It has recently been demonstrated that broadly neutralizing HA stalk-specific IgG antibodies require Fc-Fcγ receptor (FcγR) interactions for optimal protectionin vivo. Here we examine the neutrophil effector functions induced by stalk-specific antibodies. As the most abundant subset of blood leukocytes, neutrophils represent a critical innate effector cell population and serve an instrumental role in orchestrating downstream adaptive responses to influenza virus infection. Yet, the interplay of HA stalk-specific IgG, Fc-FcγR engagement, and neutrophils has remained largely uncharacterized. Using anin vitroassay to detect the production of reactive oxygen species (ROS), we show that human and mouse monoclonal HA stalk-specific IgG antibodies are able to induce the production of ROS by neutrophils, while HA head-specific antibodies do not. Furthermore, our results indicate that the production of ROS is dependent on Fc receptor (FcR) engagement and phagocytosis. We went on to assess the ability of monoclonal HA stalk-specific IgA antibodies to induce ROS. Consistent with our findings for monoclonal IgGs, only HA stalk-specific IgA antibodies elicited ROS production by neutrophils. This induction is dependent on the engagement of FcαR1. Taken together, our findings describe a novel FcR-dependent effector function induced by HA stalk-specific IgG and IgA antibodies, and importantly, our studies shed light on the mechanisms by which HA stalk-specific antibodies achieve protection.IMPORTANCEThe present study provides evidence that broadly neutralizing HA stalk-specific antibodies induce downstream Fc-mediated neutrophil effector functions. In addition to their ability to neutralize, this class of antibodies has been shown to rely on Fc-Fc receptor interactions for optimal protectionin vivo. Curiously, neutralizing antibodies that bind the HA head domain do not require such interactions. Our findings build on these previous observations and provide a more complete picture of the relationship between stalk-specific antibodies and cells of the innate immune compartment. Furthermore, our data suggest that the ability of HA stalk-specific antibodies to mediate Fc-Fc receptor engagement is epitope dependent. Overall, this work will inform the rational design of improved influenza virus vaccines and therapeutics.

scholarly journals Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates

2021 ◽  
Author(s):  
Jewell N Walters ◽  
Blake Schouest ◽  
Ami Patel ◽  
Emma L Reuschel ◽  
Katherine Schultheis ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Nonhuman Primates ◽  
First Generation ◽  
Rhesus Macaques ◽  
Natural Infection ◽  
Next Generation ◽  
Synthetic Dna ◽  
One Year ◽  
Global Population

The enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens.

Kinetics of Specific IgG Antibodies for Monitoring the Effect of Anti-Helicobacter pylori Chemotherapy

1993 ◽  
Vol 168 (3) ◽  
pp. 763-766 ◽  
Author(s):  
A. M. Hirschl ◽  
G. Brandstatter ◽  
B. Dragosics ◽  
E. Hentschel ◽  
M. Kundi ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Igg Antibodies ◽  
Specific Igg ◽  
Kinetics Of ◽  
Specific Igg Antibodies

Comparable Long-Term Persistence of Anti-FVIII Antibodies in Hemophilic E17 Mice on Different Genetic Backgrounds Despite Significant Differences in the Amplitude of the Immune Responses.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1027-1027
Author(s):  
Natalie Bauer ◽  
Christina Hausl ◽  
Rafi U. Ahmad ◽  
Bernhard Baumgartner ◽  
Hans Peter Schwarz ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Genetic Background ◽  
Neutralizing Antibodies ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Mouse Strains ◽  
Igg Antibodies ◽  
Specific Memory

Abstract About 30% of patients with severe hemophilia A develop neutralizing antibodies against FVIII (FVIII inhibitors) following replacement therapy. The type of FVIII gene mutation as well as other predisposing genetic factors contribute to the inhibitor phenotype. Based on these findings, we asked if the genetic background modulates the long-term persistence of anti-FVIII antibodies and anti-FVIII antibody secreting plasma cells in the E17 murine hemophilia model. Furthermore, we asked if the recently described inhibition of memory-B-cell re-stimulation by high doses of FVIII is influenced by the genetic background of the murine model. E17 mice on two different genetic backgrounds (C57Bl/6J and Balb/c) were treated with four doses of 200 ng human FVIII at weekly intervals. Anti-FVIII antibodies and anti-FVIII antibody secreting plasma cells were followed up to 12 months after the last dose of FVIII. Antibody titers and subclasses of antibodies (IgM, IgG1, IgG2a, IgG2b, IgG3) were measured by ELISA. Antibody secreting plasma cells in spleen and bone marrow were detected by ELISPOT as described (Hausl et al., Thromb Haemost 2002). The re-stimulation of FVIII-specific memory B cells was studied as described recently (Hausl et al., Blood 2005). Anti-FVIII antibodies and anti-FVIII antibody secreting plasma cells were first detectable in E17 Balb/c mice. IgM antibodies in the circulation and IgM secreting plasma cells in the spleen were observed after the first dose of FVIII, IgG antibodies and IgG secreting plasma cells after the second dose. No anti-FVIII antibodies after the first dose of FVIII were observed in E17 C57BL/6J mice but both IgM and IgG antibodies as well as IgM and IgG producing plasma cells were detectable after the second dose of FVIII. The antibody response involved all IgG subclasses in both mouse strains. However, IgG1 was dominant in E17 Balb/c mice whereas IgG2a was dominant in E17 C57BL/6J mice. When the in vitro restimulation of FVIII-specific memory B cells was examined, similar patterns were observed for both mouse strains. Low concentrations of FVIII between 10 and 100 ng/ml FVIII restimulated memory B cells and induced their differentiation into antibody secreting plasma cells whereas high concentrations of FVIII between 1,000 and 20,000 ng/ml FVIII inhibited memory-B-cell-restimulation. These results indicate that the dose-dependent effect of FVIII on the restimulation of FVIII-specific memory B cells does not depend on the genetic background. The major difference between both hemophilic mouse strains was the amplitude of the anti-FVIII immune response. Peak titers of anti-FVIII antibodies and peak concentrations of anti-FVIII antibody secreting plasma cells in spleen and bone marrow were significantly higher in E17 C57BL/6J mice than in E17 Balb/c mice. Whether or not higher ELISA titers correlate with higher Bethesda titers of neutralizing antibodies is currently being investigated. Despite the substantial differences in the amplitude of the immune response, anti-FVIII antibodies and anti-FVIII antibody secreting plasma cells persisted for the whole observation period of 12 months after the last dose of FVIII in both mouse strains. We conclude that the amplitude of the anti-FVIII immune response in hemophilic mice is significantly different between E17 C57BL/6J and E17 Balb/c mice. However, the persistence of the immune response is comparable.

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