scholarly journals Antibody Attributes that Predict the Neutralization and Effector Function of Polyclonal Responses to SARS-CoV-2

2021 ◽  
Author(s):  
Harini Natarajan ◽  
Shiwei Xu ◽  
Andrew R. Crowley ◽  
Ssavannah E. Butler ◽  
Joshua A. Weiner ◽  
...  
Keyword(s):  
Antibody Response ◽  
Natural Infection ◽  
Humoral Response ◽  
Mechanisms Of Action ◽  
Significant Protection ◽  
Neutralization Activity ◽  
Effector Functions ◽  
Antiviral Antibody ◽  
Response Profiles ◽  
Complement Deposition

While antibodies provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined. In this study, we employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action. To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These predictive models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion. Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions.

Escape of SARS-CoV-2 501Y.V2 variants from neutralization by convalescent plasma

2021 ◽  
Author(s):  
Sandile Cele ◽  
Inbal Gazy ◽  
Laurelle Jackson ◽  
Shi-Hsia Hwa ◽  
Houriiyah Tegally ◽  
...  
Keyword(s):  
South Africa ◽  
Antibody Response ◽  
Genome Sequencing ◽  
Receptor Binding ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Whole Genome ◽  
Receptor Binding Domain ◽  
Neutralization Activity

AbstractNew SARS-CoV-2 variants with mutations in the spike glycoprotein have arisen independently at multiple locations and may have functional significance. The combination of mutations in the 501Y.V2 variant first detected in South Africa include the N501Y, K417N, and E484K mutations in the receptor binding domain (RBD) as well as mutations in the N-terminal domain (NTD). Here we address whether the 501Y.V2 variant could escape the neutralizing antibody response elicited by natural infection with earlier variants. We were the first to outgrow two variants of 501Y.V2 from South Africa, designated 501Y.V2.HV001 and 501Y.V2.HVdF002. We examined the neutralizing effect of convalescent plasma collected from six adults hospitalized with COVID-19 using a microneutralization assay with live (authentic) virus. Whole genome sequencing of the infecting virus of the plasma donors confirmed the absence of the spike mutations which characterize 501Y.V2. We infected with 501Y.V2.HV001 and 501Y.V2.HVdF002 and compared plasma neutralization to first wave virus which contained the D614G mutation but no RBD or NTD mutations. We observed that neutralization of the 501Y.V2 variants was strongly attenuated, with IC50 6 to 200-fold higher relative to first wave virus. The degree of attenuation varied between participants and included a knockout of neutralization activity. This observation indicates that 501Y.V2 may escape the neutralizing antibody response elicited by prior natural infection. It raises a concern of potential reduced protection against re-infection and by vaccines designed to target the spike protein of earlier SARS-CoV-2 variants.

scholarly journals Glycoprotein N subtypes of human cytomegalovirus induce a strain-specific antibody response during natural infection

2009 ◽  
Vol 90 (8) ◽  
pp. 1951-1961 ◽  
Author(s):  
Christiane Burkhardt ◽  
Susanne Himmelein ◽  
William Britt ◽  
Thomas Winkler ◽  
Michael Mach
Keyword(s):  
Antibody Response ◽  
Human Cytomegalovirus ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Strain Specificity ◽  
Recombinant Viruses ◽  
Neutralization Titre ◽  
Human Sera ◽  
Antiviral Antibody ◽  
A Minor

Human cytomegalovirus (HCMV) encodes several highly polymorphic envelope glycoproteins; however, the biological relevance of this polymorphism is unclear. Glycoprotein N (gN) is one member of this polymorphic protein family. Four major gN genotypes (gN1–4) have been identified. We have tested the hypothesis that the gN polymorphism represents a mechanism to evade a neutralizing antiviral antibody response. Four recombinant viruses that differed only in the expression of the gN genotype were constructed on the genetic background of HCMV strain AD169. Exchange of gN genotypes had a minor detectable influence on virus replication, gN expression and gN–gM complex formation. Randomly selected human sera were analysed for neutralizing activity against the recombinant viruses. Of these, 70 % showed no difference in neutralizing titre between the viruses, whereas 30 % showed strain-specific neutralization. Differences in 50 % neutralization titre reached >8-fold. Viruses expressing the gN4 genotype were neutralized significantly better than those expressing the other gN genotypes. Strain specificity, or lack thereof, could not be attributed to the presence or absence of anti-gN antibodies, as all sera contained antibodies reacting with gN (as determined by ELISA). Thus, polymorphism of gN could contribute to evasion of an efficient neutralizing-antibody response and facilitate reinfection in previously seropositive individuals.

scholarly journals SARS-CoV-2-antibody response in health care workers after vaccination or natural infection in a longitudinal observational study

2021 ◽  
Author(s):  
Jonas Herzberg ◽  
Tanja Vollmer ◽  
Bastian Fischer ◽  
Heiko Becher ◽  
Ann-Kristin Becker ◽  
...  
Keyword(s):  
Immune Response ◽  
Observational Study ◽  
Antibody Response ◽  
Natural Infection ◽  
Humoral Response ◽  
Care Hospital ◽  
Igg Antibody ◽  
Humoral Immune ◽  
Longitudinal Observational Study ◽  
Antibody Ratio

Background Following a year of development, several vaccines have been approved to contain the global COVID-19 pandemic. Real world comparative data on immune response following vaccination or natural infection are rare. Methods We conducted a longitudinal observational study in employees at a secondary care hospital affected by the COVID-19 pandemic. Comparisons were made about the presence of anti-SARS-CoV-2 immunglobulin G (IgG) antibody ratio after natural infection, or vaccination with one or two doses of BioNTech/Pfizer (BNT162b2), or one dose of AstraZenca (Vaxzevria) vaccine. Results We found a 100% humoral response rate in participants after 2 doses of BNT162b2 vaccine. The antibody ratio in participants with one dose BNT162b2 and Vaxzevria did not differ significantly to those with previous PCR-confirmed infection, whereas this was significantly lower in comparison to two doses of BioNTech/Pfizer. We could not identify a correlation with previous comorbidities, obesity or age within this study. Smoking showed a negative effect on the antibody response (p=0.006) Conclusion Our data provide an overview about humoral immune response after natural SARS-CoV-2 infection or following vaccination, and supports the usage of booster vaccinations, especially in patients after a natural SARS-CoV-2 infection.

scholarly journals Filovirus Neutralising Antibodies: Mechanisms of Action and Therapeutic Application

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1201
Author(s):  
Alexander Hargreaves ◽  
Caolann Brady ◽  
Jack Mellors ◽  
Tom Tipton ◽  
Miles W. Carroll ◽  
...  
Keyword(s):  
Antibody Response ◽  
Ebola Virus ◽  
Immune Escape ◽  
Case Fatality ◽  
Humoral Response ◽  
Mechanisms Of Action ◽  
Neutralising Antibodies ◽  
Virus Structure ◽  
Viral Haemorrhagic Fever ◽  
And Function

Filoviruses, especially Ebola virus, cause sporadic outbreaks of viral haemorrhagic fever with very high case fatality rates in Africa. The 2013–2016 Ebola epidemic in West Africa provided large survivor cohorts spurring a large number of human studies which showed that specific neutralising antibodies played a key role in protection following a natural Ebola virus infection, as part of the overall humoral response and in conjunction with the cellular adaptive response. This review will discuss the studies in survivors and animal models which described protective neutralising antibody response. Their mechanisms of action will be detailed. Furthermore, the importance of neutralising antibodies in antibody-based therapeutics and in vaccine-induced responses will be explained, as well as the strategies to avoid immune escape from neutralising antibodies. Understanding the neutralising antibody response in the context of filoviruses is crucial to furthering our understanding of virus structure and function, in addition to improving current vaccines & antibody-based therapeutics.

scholarly journals Nano-Microparticle Platforms in Developing Next-Generation Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 606
Author(s):  
Giuseppe Cappellano ◽  
Hugo Abreu ◽  
Chiara Casale ◽  
Umberto Dianzani ◽  
Annalisa Chiocchetti
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cell Response ◽  
Humoral Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Next Generation ◽  
Emerging Viruses ◽  
Whole Cells ◽  
Effector Functions

The first vaccines ever made were based on live-attenuated or inactivated pathogens, either whole cells or fragments. Although these vaccines required the co-administration of antigens with adjuvants to induce a strong humoral response, they could only elicit a poor CD8+ T-cell response. In contrast, next-generation nano/microparticle-based vaccines offer several advantages over traditional ones because they can induce a more potent CD8+ T-cell response and, at the same time, are ideal carriers for proteins, adjuvants, and nucleic acids. The fact that these nanocarriers can be loaded with molecules able to modulate the immune response by inducing different effector functions and regulatory activities makes them ideal tools for inverse vaccination, whose goal is to shut down the immune response in autoimmune diseases. Poly (lactic-co-glycolic acid) (PLGA) and liposomes are biocompatible materials approved by the Food and Drug Administration (FDA) for clinical use and are, therefore, suitable for nanoparticle-based vaccines. Recently, another candidate platform for innovative vaccines based on extracellular vesicles (EVs) has been shown to efficiently co-deliver antigens and adjuvants. This review will discuss the potential use of PLGA-NPs, liposomes, and EVs as carriers of peptides, adjuvants, mRNA, and DNA for the development of next-generation vaccines against endemic and emerging viruses in light of the recent COVID-19 pandemic.

scholarly journals Antibody response to common viruses and human leukocyte antigen-DRB1 in pediatric multiple sclerosis

2012 ◽  
Vol 19 (7) ◽  
pp. 891-895 ◽  
Author(s):  
Emmanuelle Waubant ◽  
Ellen M Mowry ◽  
Lauren Krupp ◽  
Tanuja Chitnis ◽  
E Ann Yeh ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Antibody Response ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Humoral Response ◽  
Nuclear Antigen ◽  
Leukocyte Antigen ◽  
Epstein Barr ◽  
Humoral Responses ◽  
Hsv 1

Background: As remote infections with common herpes viruses are associated with modulation of the risk of multiple sclerosis (MS), we hypothesized that antibody concentrations against these viruses may further modify risk. As many common viruses are first encountered during childhood, pediatric MS offer a unique opportunity to investigate more closely their influence on susceptibility. Our aim was to determine if MS patients who were positive for these viruses had higher levels of antibodies to these viruses. We also assessed whether human leukocyte antigen (HLA)-DRB1*1501 genotype influenced viral antibody levels. Methods: Antibody response levels toward Epstein Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV)-1, and HLA-DRB1*1501 status were determined in pediatric MS patients ( n=189) and controls ( n=38). Multivariate analyses were used, adjusted for age, gender, race, ethnicity and use of disease-modifying therapies. Results: The antibody concentrations against EBV (Epstein-Barr nuclear antigen 1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA)), CMV and HSV-1 were similar between pediatric MS patients and controls positive for seroconversion against the virus of interest. EBNA-1 humoral responses were higher in HLA-DRB1 positive individuals ( p=0.005) whereas other viral humoral responses were similar in HLA-DRB1 positive and negative individuals. Conclusion: Among those positive for EBNA-1, MS patients did not have higher levels of antibody response to EBNA-1: however, titers for EBNA-1 were higher in those who were HLA-DRB1 positive. This suggests that genotype might influence the humoral response to EBV. Whether other genotypes influence antibody response to other viruses remains to be determined.

scholarly journals Naturally induced humoral response against Plasmodium vivax reticulocyte binding protein 2P1

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jenni Hietanen ◽  
Anongruk Chim-ong ◽  
Jetsumon Sattabongkot ◽  
Wang Nguitragool
Keyword(s):  
Plasmodium Vivax ◽  
Vaccine Development ◽  
Natural Infection ◽  
Humoral Response ◽  
Human Antibody ◽  
Asymptomatic Carriers ◽  
Erythrocyte Invasion ◽  
Human Proteins ◽  
Human Immune Response

Abstract Background Plasmodium vivax is the most prevalent malaria parasite in many countries. A better understanding of human immunity to this parasite can provide new insights for vaccine development. Plasmodium vivax Reticulocyte Binding Proteins (RBPs) are key parasite proteins that interact with human proteins during erythrocyte invasion and are targets of the human immune response. The aim of this study is to characterize the human antibody response to RBP2P1, the most recently described member of the RBP family. Methods The levels of total IgG and IgM against RBP2P1 were measured using plasmas from 68 P. vivax malaria patients and 525 villagers in a malarious village of western Thailand. The latter group comprises asymptomatic carriers and healthy uninfected individuals. Subsets of plasma samples were evaluated for anti-RBP2P1 IgG subtypes and complement-fixing activity. Results As age increased, it was found that the level of anti-RBP2P1 IgG increased while the level of IgM decreased. The main anti-RBP2P1 IgG subtypes were IgG1 and IgG3. The IgG3-seropositive rate was higher in asymptomatic carriers than in patients. The higher level of IgG3 was correlated with higher in vitro RBP2P1-mediated complement fixing activity. Conclusions In natural infection, the primary IgG response to RBP2P1 was IgG1 and IgG3. The predominance of these cytophilic subtypes and the elevated level of IgG3 correlating with complement fixing activity, suggest a possible role of anti-RBP2P1 antibodies in immunity against P. vivax.

scholarly journals Fc-Receptor Targeted Therapies for the Treatment of Myasthenia gravis

2021 ◽  
Vol 22 (11) ◽  
pp. 5755
Author(s):  
Christian W. Keller ◽  
Marc Pawlitzki ◽  
Heinz Wiendl ◽  
Jan D. Lünemann
Keyword(s):  
Myasthenia Gravis ◽  
Acetylcholine Receptors ◽  
Postsynaptic Membrane ◽  
Fc Receptor ◽  
Igg Antibodies ◽  
Effector Functions ◽  
Disease Remission ◽  
Disease Mechanisms ◽  
First Choice ◽  
Complement Deposition

Myasthenia gravis (MG) is an autoimmune disease in which immunoglobulin G (IgG) antibodies (Abs) bind to acetylcholine receptors (AChR) or to functionally related molecules in the postsynaptic membrane at the neuromuscular junction. IgG crystallizable fragment (Fc)-mediated effector functions, such as antibody-dependent complement deposition, contribute to disease development and progression. Despite progress in understanding Ab-mediated disease mechanisms, immunotherapy of MG remained rather unspecific with corticosteroids and maintenance with immunosuppressants as first choice drugs for most patients. More specific therapeutic IgG Fc-based platforms that reduce serum half-life or effector functions of pathogenic MG-related Abs are currently being developed, tested in clinical trials or have recently been successfully translated into the clinic. In this review, we illustrate mechanisms of action and clinical efficacies of emerging Fc-mediated therapeutics such as neonatal Fc receptor (FcRn)-targeting agents. Furthermore, we evaluate prospects of therapies targeting classical Fc receptors that have shown promising therapeutic efficacy in other antibody-mediated conditions. Increased availability of Fc- and Fc receptor-targeting biologics might foster the development of personalized immunotherapies with the potential to induce sustained disease remission in patients with MG.

scholarly journals Mucosal versus systemic antibody responses to SARS-CoV-2 antigens in COVID-19 patients

2020 ◽  
Author(s):  
Baweleta Isho ◽  
Kento T Abe ◽  
Michelle Zuo ◽  
Alainna J Jamal ◽  
Bhavisha Rathod ◽  
...  
Keyword(s):  
Antibody Response ◽  
Upper Airway ◽  
Mucosal Immune Response ◽  
Antibody Responses ◽  
Igg Antibodies ◽  
Blood Draw ◽  
Neutralization Activity ◽  
Surrogate Measure ◽  
Antibody Levels ◽  
Negative Controls

While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the antibody response in the oral cavity is likely an important parameter that influences the course of infection, but how it correlates to the antibody response in serum is not known. Here, we profile by enzyme linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor binding domain (RBD) in serum (n=496) and saliva (n=90) of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared to negative controls. Anti-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16-30 days PSO. Whereas anti-CoV-2 IgA and IgM antibodies rapidly decayed, IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. In a surrogate neutralization ELISA (snELISA), neutralization activity peaks by 31-45 days PSO and slowly declines, though a clear drop is detected at the last blood draw (105-115 days PSO). Lastly, 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 systemic and mucosal humoral IgG antibodies are maintained in the majority of COVID-19 patients for at least 3 months PSO. Based on their correlation with each other, IgG responses in saliva may serve as a surrogate measure of systemic immunity.

scholarly journals Durability of SARS-CoV-2 Antibodies from Natural Infection in Children and Adolescents

2021 ◽  
Author(s):  
Sarah E Messiah ◽  
Frances A Brito ◽  
Harold W Kohl ◽  
Stacia M DeSantis ◽  
Melissa A Valerio-Shewmaker ◽  
...  
Keyword(s):  
Antibody Response ◽  
Natural Infection ◽  
Significant Proportion ◽  
Population Based ◽  
Healthy Weight ◽  
Blood Draw ◽  
True Incidence ◽  
Related Symptom ◽  
Symptom Status ◽  
Antibody Tests

Background. Recent data suggest the SARS-CoV-2 Delta (B.1.617.2) variant is more transmissible among children compared to the Alpha (B.1.1.7) variant. The true incidence and longitudinal presence of antibody response to SARS-CoV-2 infection is not known, however. We provided estimates of antibody response using Texas Coronavirus Antibody REsponse Survey (Texas CARES) data, a prospective population-based seroprevalence project designed to assess antibody status over time among the general population throughout the state. Methods. In October 2020 Texas CARES began enrolling adults (aged 20-80 years) and children (aged 5-19 years). Participants were offered a series of three SARS-CoV-2 antibody tests over 6-8 months, or every 2-3 months that includes the immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test). Descriptive characteristics and COVID-19 infection-related symptom status was determined by questionnaire at the time of enrollment and prior to each successive blood draw. This analysis included participants ages 5-to-19 years old who have completed all three antibody assessments. Results. From our sample (n=159; mean age 12.5 years, SD 3.6), 96% of those with evidence of nucleocapsid antibodies at baseline assessment continued to have antibodies > six months later (mean 7.0 months, SD 0.97). There was no difference in the presence of antibodies by symptom status (asymptotic versus symptomatic) or severity (mild-moderate versus severe), sex, age group, or body mass index group (underweight, healthy weight, overweight, obesity) over the three antibody measurement timepoints. Conclusions. These results suggest that infection-induced antibodies persist and thus may provide some protection against future infection for at least half a year. 57.9% of the sample were negative for infection-induced antibodies at their third measurement point, suggesting a significant proportion of children have still not acquired natural infection.

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