A multiplex serological assay for the characterization of IgG immune response to SARS-CoV-2

In the fight against SARS-COV-2, the development of serological assays based on different antigenic domains represent a versatile tool to get a comprehensive picture of the immune response or differentiate infection from vaccination beyond simple diagnosis. Here we use a combination of the Nucleoprotein (NP), the Spike 1 (S1) and Spike 2 (S2) subunits, and the receptor binding domain (RBD) and N-terminal domain (NTD) of the Spike antigens from the CoViDiag® multiplex IgG assay, to follow the immune response to SARS-CoV-2 infection over a long time period and depending on disease severity. Using a panel of 209 sera collected from 61 patients up to eight months after infection, we observed that most patients develop an immune response against multiple viral epitope, but anti-S2 antibodies seemed to last longer. For all the tested IgGs, we have found higher responses for hospitalized patients than for non-hospitalized ones. Moreover the combination of the five different IgG responses increased the correlation to the neutralizing antibody titers than if considered individually. Multiplex immunoassays have the potential to improve diagnostic performances, especially for ancient infection or mild form of the disease presenting weaker antibody responses. Also the combined detection of anti-NP and anti-Spike-derived domains can be useful to differentiate vaccination from viral infection and accurately assess the antibody potential to neutralize the virus.

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A multiplex serological assay for the characterization of IgG immune response to SARS-CoV-2

10.1101/2021.09.23.21262329 ◽

2021 ◽

Author(s):

Etienne Brochot ◽

Vianney Souplet ◽

Pauline Follet ◽

Pauline Ponthieu ◽

Christophe Olivier ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibody ◽

Viral Epitope ◽

Time Period ◽

Versatile Tool ◽

Comprehensive Picture ◽

Long Time ◽

Antibody Titers ◽

Combined Detection

Background: In the fight against SARS-COV-2, the development of serological assays based on different antigenic domains represent a versatile tool to get a comprehensive picture of the immune response or differentiate infection from vaccination beyond simple diagnosis. Objectives: Here we use a combination of the Nucleoprotein (NP), the Spike 1 (S1) and Spike 2 (S2) subunits, and the receptor binding domain (RBD) and N-terminal domain (NTD) of the Spike antigens from the Syrius-CoViDiag multiplex IgG assay, to follow the immune response to SARS-CoV-2 infection over a long time period and depending on disease severity. Results: Using a panel of 209 sera collected from 61 patients up to eight months after infection, we observed that most patients develop an immune response against multiple viral epitope, but anti-S2 antibodies seemed to last longer. For all the tested IgGs, we have found higher titers for hospitalized patients than for non-hospitalized ones. Moreover the combination of the five different IgG titers increased the correlation to the neutralizing antibody titers than if considered individually. Conclusion: Multiplex immunoassays have the potential to improve diagnostic performances, especially for ancient infection or mild form of the disease presenting weaker antibody titers. Also the combined detection of anti-NP and anti-Spike-derived domains can be useful to differentiate vaccination from viral infection and accurately assess the antibody potential to neutralize the virus.

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Characterization of the Humoral Immune Response Induced after Infection with Atypical Porcine Pestivirus (APPV)

Viruses ◽

10.3390/v11100880 ◽

2019 ◽

Vol 11 (10) ◽

pp. 880 ◽

Cited By ~ 4

Author(s):

Gökce Nur Cagatay ◽

Denise Meyer ◽

Michael Wendt ◽

Paul Becher ◽

Alexander Postel

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Humoral Immune ◽

Neutralizing Capacity ◽

Antibody Titers ◽

Antibody Levels ◽

Congenital Tremor

Atypical porcine pestivirus (APPV) is a widely distributed pathogen causing congenital tremor (CT) in piglets. So far, no data are available regarding the humoral immune response against APPV. In this study, piglets and their sows from an affected herd were tested longitudinally for viral genome and antibodies. APPV genome was detected in the majority of the piglets (14/15) from CT affected litters. Transient infection of gilts was observed. Kinetics of Erns- and E2-specific antibodies and their neutralizing capacity were determined by recently (Erns) and newly (E2) developed antibody ELISAs and virus neutralization assays. Putative maternally derived antibodies (MDA) were detected in most piglets, but displayed only low to moderate neutralizing capacity (ND50 ≤ 112). Horizontal APPV transmission occurred when uninfected and infected piglets were mingled on the flat deck. Horizontally infected piglets were clinically inapparent and showed only transient viremia with subsequently consistently high E2 antibody levels. For piglets from CT affected litters, significantly lower neutralizing antibody titers were observed. Results indicate that E2 represents the main target of neutralizing antibodies. Characterization of the humoral immune response against APPV will help to provide valuable serological diagnosis, to understand the epidemiology of this novel pathogen, and to implement tailored prevention strategies.

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Is the Prevalence of Leishmania infantum Linked to Breeds in Dogs? Characterization of Seropositive Dogs in Ibiza

Animals ◽

10.3390/ani11092579 ◽

2021 ◽

Vol 11 (9) ◽

pp. 2579

Author(s):

Maria Edo ◽

Pablo Jesús Marín-García ◽

Lola Llobat

Keyword(s):

Immune Response ◽

Leishmania Infantum ◽

Protozoan Parasite ◽

Disease Stage ◽

Doberman Pinscher ◽

Th2 Immune Response ◽

Mediterranean Island ◽

Antibody Titers ◽

The Relationship

Leishmaniosis is an important zoonotic protozoan disease primarily spread to the Mediterranean region by Leishmania infantum, the predominant protozoan species, which accounts for the majority of cases. Development of disease depends on the immune response of the definitive host and, predictably, their genetic background. Recent studies have revealed breed-typical haplotypes that are susceptible to the spread of the protozoan parasite. The objective of this study was to analyze the prevalence of leishmaniosis on a Mediterranean island and determine the relationship between disease prevalence and breed. In addition, information on seropositive animals was recorded to characterize animals affected by the disease. To study the prevalence, a total of 3141 dogs were analyzed. Of these, the 149 infected animals were examined for age, sex, antibody titer, and disease stage. We observed a prevalence of 4.74%, which varied between breeds (p < 0.05). The Doberman Pinscher and Boxer breeds had the highest prevalence of leishmaniosis. Significant differences were observed between breeds with common ancestors, emphasizing the important genetic component. Finally, regarding the characterization of seropositive animals, the distribution is similar to other studies. We discovered a relationship (p < 0.05) between the number of antibody titers and the clinical disease stage, which was also present in Leishmania infantum, suggesting that the development of the disease depends on the humoral or Th2 immune response with ineffective antibodies.

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Effect of a booster-dose of rabies vaccine on the duration of virus neutralizing antibody titers in bovines

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86821998000400006 ◽

1998 ◽

Vol 31 (4) ◽

pp. 367-371 ◽

Cited By ~ 5

Author(s):

Avelino Albas ◽

Paulo Eduardo Pardo ◽

Albério Antonio Barros Gomes ◽

Fernanda Bernardi ◽

Fumio Honma Ito

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Booster Dose ◽

Neutralization Test ◽

Neutralizing Antibody ◽

Rabies Vaccine ◽

Western Region ◽

Humoral Immune ◽

Paulo State ◽

Antibody Titers

Humoral immune response using inactivated rabies vaccine was studied in 35 nelore cross-bred bovines of western region of São Paulo state. Ninety days after vaccination, 13 (92.8%) animals presented titers 30.5IU/ml, through mouse neutralization test. After 180 days, 9 (64.3%) sera showed titers 30.5IU/ml, after 270 days, only one (7.1%) showed a titer of 0.51IU/ml, and after 360 days, all animals showed titers < 0.5IU/ml. Group of animals receiving booster dose 30 days after vaccination presented, two months after, all with titers > 0.5IU/ml. At 180 days, 17 (80.9%) sera presented titers > 0.5IU/ml; at 270 days, 15 (71.4%), with titers 30.5IU/ml and at 360 days, 4 (19.0%), with titers 30.5IU/ml. Booster-dose ensured high levels of neutralizing antibodies for at least three months, and 240 days after revaccination, 71.4% of animals were found with titers 30.5IU/ml.

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Mechanisms of Dysregulated Humoral and Cellular Immunity by SARS-CoV-2

Pathogens ◽

10.3390/pathogens9121027 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1027

Author(s):

Nima Taefehshokr ◽

Sina Taefehshokr ◽

Bryan Heit

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Cell Function ◽

Adaptive Immune Response ◽

Neutralizing Antibody ◽

Humoral And Cellular Immunity ◽

Cell Responses ◽

Adaptive Immune ◽

Antibody Titers

The current coronavirus disease 2019 (COVID-19) pandemic, a disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), was first identified in December 2019 in China, and has led to thousands of mortalities globally each day. While the innate immune response serves as the first line of defense, viral clearance requires activation of adaptive immunity, which employs B and T cells to provide sanitizing immunity. SARS-CoV-2 has a potent arsenal of mechanisms used to counter this adaptive immune response through processes, such as T cells depletion and T cell exhaustion. These phenomena are most often observed in severe SARS-CoV-2 patients, pointing towards a link between T cell function and disease severity. Moreover, neutralizing antibody titers and memory B cell responses may be short lived in many SARS-CoV-2 patients, potentially exposing these patients to re-infection. In this review, we discuss our current understanding of B and T cells immune responses and activity in SARS-CoV-2 pathogenesis.

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Microneedle-Based Intradermal Delivery of the Anthrax Recombinant Protective Antigen Vaccine

Infection and Immunity ◽

10.1128/iai.01210-06 ◽

2006 ◽

Vol 74 (12) ◽

pp. 6806-6810 ◽

Cited By ~ 84

Author(s):

John A. Mikszta ◽

John P. Dekker ◽

Noel G. Harvey ◽

Cheryl H. Dean ◽

John M. Brittingham ◽

...

Keyword(s):

Immune Response ◽

Immunoglobulin G ◽

Protective Antigen ◽

Neutralizing Antibody ◽

Antigen Vaccine ◽

Intradermal Delivery ◽

Antibody Titers ◽

Sparing Effect ◽

Booster Inoculation ◽

Recombinant Protective Antigen

ABSTRACT The recombinant protective antigen (rPA) of Bacillus anthracis is a promising anthrax vaccine. We compared serum immunoglobulin G levels and toxin-neutralizing antibody titers in rabbits following delivery of various doses of vaccine by microneedle-based intradermal (i.d.) delivery or intramuscular (i.m.) injection using conventional needles. Intradermal delivery required less antigen to induce levels of antibody similar to those produced via i.m. injection during the first 2 weeks following primary and booster inoculation. This dose-sparing effect was less evident at the later stages of the immune response. Rabbits immunized i.d. with 10 μg of rPA displayed 100% protection from aerosol spore challenge, while i.m. injection of the same dose provided slightly lower protection (71%). Groups immunized with lower antigen doses were partially protected (13 to 29%) regardless of the mode of administration. Overall, our results suggest rPA formulated with aluminum adjuvant and administered to the skin by a microneedle-based device is as efficacious as i.m. vaccination.

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On the Potential of the RST-FLARE Algorithm for Gas Flaring Characterization from Space

Sensors ◽

10.3390/s18082466 ◽

2018 ◽

Vol 18 (8) ◽

pp. 2466 ◽

Cited By ~ 6

Author(s):

Mariapia Faruolo ◽

Teodosio Lacava ◽

Nicola Pergola ◽

Valerio Tramutoli

Keyword(s):

Niger Delta ◽

Gas Flaring ◽

Niger Delta Region ◽

Time Period ◽

Independent Information ◽

Long Time ◽

Satellite Methods ◽

Annual Scale ◽

Volume Estimates

An effective characterization of gas flaring is hampered by the lack of systematic, complete and reliable data on its magnitude and spatial distribution. In the last years, a few satellite methods have been developed to provide independent information on gas flaring activity at global, national and local scale. Among these, a MODIS-based method, aimed at the computation of gas flared volumes by an Italian plant, was proposed. In this work, a more general version of this approach, named RST-FLARE, has been developed to provide reliable information on flaring sites localization and gas emitted volumes over a long time period for the Niger Delta region, one of the top five gas flaring areas in the world. Achieved results showed a good level of accuracy, in terms of flaring sites localization (95% of spatial match) and volume estimates (mean bias between in 16% and 20%, at annual scale and 2–9% in the long period) when compared to independent data, provided both by other satellite techniques and national/international organizations. Outcomes of this work seem to indicate that RST-FLARE can be used to provide, at different geographic scales, quite accurate data on gas flaring, suitable for monitoring purposes for governments and local authorities.

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Memory immune response: a major challenge in vaccination

BioMolecular Concepts ◽

10.1515/bmc-2012-0010 ◽

2012 ◽

Vol 3 (5) ◽

pp. 479-486 ◽

Cited By ~ 7

Author(s):

Antonella Prisco ◽

Piergiuseppe De Berardinis

Keyword(s):

Gene Expression ◽

Immune Response ◽

Vaccine Development ◽

Immune Memory ◽

Gene Expression Signatures ◽

Antibody Titers ◽

Memory Immune Response ◽

Protective Threshold

AbstractA crucial challenge for vaccine development is to design vaccines that induce a long-lasting protective immune response, i.e., immune memory. The persistence of antigen-specific antibody titers over a protective threshold, and the ability to exibit a ‘recall response’ to a subsequent encounter with an antigen have long been the only measurable correlates of vaccine take and immune memory development, suffering from the disadvantage of relying on long-term monitoring of the immune response. In the last few years, advances in the technologies for the identification and characterization of the cell subsets and molecular pathways involved in the immune response to vaccination have allowed innovative approaches to the identification of early correlates of immune memory. In this review, we discuss recent data and hypotheses on early correlates of the development of immune memory, with special emphasis on the gene expression signatures that underlie the self-renewal ability of some lymphocyte subsets, and their similarities with gene expression signatures in stem cells.

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Differential serological and neutralizing antibody dynamics after an infection by a single SARS-CoV-2 strain

10.21203/rs.3.rs-77625/v1 ◽

2020 ◽

Author(s):

Emmanuelle Billon-Denis ◽

Audrey Ferrier-Rembert ◽

Annabelle Garnier ◽

Laurence Cheutin ◽

Clarisse Vigne ◽

...

Keyword(s):

Immune Response ◽

Receptor Binding ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Binding Domain ◽

Clinical Severity ◽

Individual Factors ◽

Receptor Binding Domain ◽

Antibody Titers ◽

Antibody Dynamics

Abstract BackgroundWe report here the case of two coworkers infected by the same SARS-CoV-2 strain, presenting two different immunological outcomes. CaseOne patient presented a strong IgG anti-receptor-binding domain immune response correlated with a low and rapidly decreasing titer of neutralizing antibodies. The other patient had similar strong IgG anti-receptor-binding domain immune response but high neutralizing antibody titers. Discussion and ConclusionThus, host individual factors may be the main drivers of the immune response varying with age and clinical severity.

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VACCINATION-RELATED CLINICAL PARAMETERS AND VIRUS-NEUTRALIZATION LEVEL AFTER SMALLPOX REVACCINATION

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-hiv-1337 ◽

2019 ◽

Author(s):

O. Ermilova ◽

Z. Gin’ko ◽

V. Belyavskaya

Keyword(s):

Immune Response ◽

Adverse Events ◽

Vaccinia Virus ◽

Antibody Level ◽

Clinical Signs ◽

Neutralizing Antibody ◽

Smallpox Vaccine ◽

Protective Antibody ◽

Antibody Titers ◽

Vaccination Period

Mass vaccination with vaccinia virus resulted in smallpox eradication, that was later cancelled due to potential of developing severe complications. Reappraisal of scientific interest to smallpox vaccine was accounted for by emerged threat of using relevant virus as a bioweapon as well as increased frequency of orthopoxvirus infections paralleled with decline in population immunity. The vaccinia virus is also used as a vector for generating recombinant vaccines. Understanding mechanisms behind formation of immune response and opportunity for forecasting its modality may allow to avoid potential adverse events and excessive immunization.The aim of the study was to assess a link between humoral immunity, clinical signs related to vaccination period, adult sex and age characteristics in subjects received several doses of vaccinia virus. We examined vaccination-coupled clinical data obtained from 135 subjects revaccinated with a smallpox vaccine for 2-10 times. It was found that 95% and 5% vaccine recipients experienced mild or moderate vaccination-related signs, respectively.Inoculation skin lesions were observed in 127 subjects (94.1%), whereas 22% vaccine recipients experienced local and systemic adverse events. Mild vs. moderate vaccine signs group manifested greater hyperemia (p=0.04), scabbing (p=0.01), and duration of healing time (p=0.001). Younger subjects (p=0.03) and more frequent axillary adenopathy (p<0.001) were observed in moderate vs. mild vaccination period were at lower rate (p = 0.03), lymphadenopathy developed more often during moderate vaccination period (p<0.001).Vaccinia virus-neutralizing antibody titers were measured in 54 subjects by using plaque reduction neutralization tests. It was noted that protective antibody level tended to rise in females vs. males. A negative correlation between antibody titers and hyperemia degree was observed. Frequent axillary adenopathy was associated with higher serum protective antibody level. Vaccinia-virus neutralizing antibody titers were not associated with presence and size of inoculation lesion, elimination of skin crusts, age and previous vaccination records. The clinical variability and immune response after applying this vaccine by similar vaccination protocol would be accounted for by individual genetic differences remains to be further explored.

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