scholarly journals Antibody response to SARS-CoV-2 infection and BNT162b2 vaccine in Israel

2021 ◽  
Author(s):  
Guy Shapira ◽  
Ramzia Abu Hamad ◽  
Chen Weiner ◽  
Nir Rainy ◽  
Reut Sorek-Abramovich ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Host Cells ◽  
Spike Protein ◽  
Igg Antibodies ◽  
Age And Gender ◽  
Specific Igg ◽  
And Gender ◽  
Specific Igg Antibodies

Neutralizing antibodies targeting the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) block viral entry to host cells, preventing disease and further spread of the pathogen. The presence of SARS-CoV-2 antibodies in serum is a reliable indicator of infection, used epidemiologically to estimate the prevalence of infection and clinically as a measurement of an antigen-specific immune response. In this study, we analyzed serum Spike protein-specific IgG antibodies from 26,170 samples, including convalescent individuals who had coronavirus disease 2019 (COVID-19) and recipients of the BNT162b2 vaccine. We find distinct serological patterns in COVID-19 convalescent and vaccinated individuals, correlated with age and gender and the presence symptoms.

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 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.

Enhanced immunogenicity of a synthetic DNA vaccine expressing consensus SARS-CoV-2 Spike protein using needle-free immunization

2021 ◽  
Author(s):  
Sawsan S Alamri ◽  
Khalid A Alluhaybi ◽  
Rowa Y Alhabbab ◽  
Abdullah Algaissi ◽  
Sarah Almahboub ◽  
...  
Keyword(s):  
Immune Response ◽  
Dna Vaccine ◽  
Mammalian Cells ◽  
Cellular Response ◽  
Igg Antibodies ◽  
Free System ◽  
Mammalian Expression ◽  
Specific Igg ◽  
Needle Injection ◽  
Specific Igg Antibodies

AbstractThe ongoing global pandemic of Coronavirus Disease 2019 (COVID-19) calls for an urgent development of effective and safe prophylactic and therapeutic measures. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein is a major immunogenic and protective protein, and plays a crucial role in viral pathogenesis. In this study, we successfully constructed a synthetic codon-optimized DNA-based vaccine as a countermeasure against SARS-CoV-2; denoted as VIU-1005. The design was based on the synthesis of codon-optimized coding sequence for optimal mammalian expression of a consensus full-length S glycoprotein. The successful construction of the vaccine was confirmed by restriction digestion and sequencing, and the protein expression of the S protein was confirmed by western blot and immunofluorescence staining in mammalian cells. The immunogenicity of the vaccine was tested in two mouse models (BALB/c and C57BL/6J). Th1-skewed systemic S-specific IgG antibodies and neutralizing antibodies (nAbs) were significantly induced in both models four weeks post three injections with 100 μg of the VIU-1005 vaccine via intramuscular needle injection but not intradermal or subcutaneous routes. Importantly, such immunization induced long-lasting IgG response in mice that lasted for at least 6 months. Interestingly, using a needle-free system, we showed an enhanced immunogenicity of VIU-1005 in which lower doses such as 25-50 μg or less number of doses were able to elicit significantly high levels of Th1-biased systemic S-specific IgG antibodies and nAbs via intramuscular immunization compared to needle immunization. Compared to the intradermal needle injection which failed to induce any significant immune response, intradermal needle-free immunization elicited robust Th1-biased humoral response similar to that observed with intramuscular immunization. Furthermore, immunization with VIU-1005 induced potent S-specific cellular response as demonstrated by the significantly high levels of IFN-γ, TNF and IL-2 cytokines production in memory CD8+ and CD4+ T cells in BALB/c mice. Together, our results demonstrate that the synthetic VIU-1005 candidate DNA vaccine is highly immunogenic and capable of inducing long-lasting and Th1-skewed immune response in mice. Furthermore, we show that the use of needle-free system could enhance the immunogenicity and minimize doses needed to induce protective immunity in mice, supporting further preclinical and clinical testing of this candidate vaccine.

scholarly journals Engineered ACE2 receptor traps potently neutralize SARS-CoV-2

2020 ◽  
Vol 117 (45) ◽  
pp. 28046-28055 ◽  
Author(s):  
Anum Glasgow ◽  
Jeff Glasgow ◽  
Daniel Limonta ◽  
Paige Solomon ◽  
Irene Lui ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Surface Display ◽  
Random Mutagenesis ◽  
Yeast Surface Display ◽  
Host Cells ◽  
Spike Protein ◽  
Receptor Protein ◽  
Yeast Surface

An essential mechanism for severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection begins with the viral spike protein binding to the human receptor protein angiotensin-converting enzyme II (ACE2). Here, we describe a stepwise engineering approach to generate a set of affinity optimized, enzymatically inactivated ACE2 variants that potently block SARS-CoV-2 infection of cells. These optimized receptor traps tightly bind the receptor binding domain (RBD) of the viral spike protein and prevent entry into host cells. We first computationally designed the ACE2–RBD interface using a two-stage flexible protein backbone design process that improved affinity for the RBD by up to 12-fold. These designed receptor variants were affinity matured an additional 14-fold by random mutagenesis and selection using yeast surface display. The highest-affinity variant contained seven amino acid changes and bound to the RBD 170-fold more tightly than wild-type ACE2. With the addition of the natural ACE2 collectrin domain and fusion to a human immunoglobulin crystallizable fragment (Fc) domain for increased stabilization and avidity, the most optimal ACE2 receptor traps neutralized SARS-CoV-2–pseudotyped lentivirus and authentic SARS-CoV-2 virus with half-maximal inhibitory concentrations (IC50s) in the 10- to 100-ng/mL range. Engineered ACE2 receptor traps offer a promising route to fighting infections by SARS-CoV-2 and other ACE2-using coronaviruses, with the key advantage that viral resistance would also likely impair viral entry. Moreover, such traps can be predesigned for viruses with known entry receptors for faster therapeutic response without the need for neutralizing antibodies isolated from convalescent patients.

scholarly journals Examination of convalescents after West Nile fever for the specific IgM, IgG and neutralizing antibodies

2016 ◽  
Vol 21 (2) ◽  
pp. 82-86
Author(s):  
Alla R. Azaryan ◽  
A. A Kozlova ◽  
A. P Grishanova ◽  
E. I Ivashchenko ◽  
G. L Shendo ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Igg Antibodies ◽  
West Nile Fever ◽  
Serum Samples ◽  
West Nile ◽  
Negative Results ◽  
Igm Elisa ◽  
Control Research ◽  
Specific Igg ◽  
Specific Igg Antibodies

The examination was executed in the Astrakhan region over 2013-2014 with participation of three laboratories. In 26 convalescents after West Nile Fever (WNF) with the serological confirmed diagnosis of WNF blood sera were examined. Neurological form of WNF was observed in 8 cases, and febrile form - in 8 convalescents. Sera have been collected in 243-358 days, on average, in 308 days after the beginning of a disease. For their examination there were used IFA-IgM ELISA (MAC-ELISA), IgG ELISA methods as well as neutralization test in Vero E6 cell culture. The results of the examination in 24 of 26 patients (92, 3%) for IgM antibodies to the virus WNF were negative. In two convalescents according to the laboratories in Astrakhan and Moscow in sera there were observed low titers of IgM (1:400) with minor indices of sera optical density (0.3 to 0.4) and negative results in the Volgograd Plague Control Research Institute. Serum samples of other two convalescents were weakly positive or questionable in testing in Volgograd, but were negative when examined in the Institute of Virology. Specific IgG antibodies were detected in 23 of 26 convalescents (88.5%), neutralizing in 22 of 24 (91.7 %). These data confirm the adequacy of the criteria and tactics for WNF serodiagnosis adopted in Russia based on the application of the MAC -ELISA (IFA - IgM).

scholarly journals Stable IgG-antibody levels in patients with mild SARS-CoV-2 infection

2021 ◽  
Author(s):  
Thomas Akerlund ◽  
Katherina Zakikhany ◽  
Charlotta Lofstrom ◽  
Evelina Lindmark ◽  
Henrik Kallberg ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Spike Protein ◽  
Igg Antibodies ◽  
Serum Samples ◽  
Igg Antibody ◽  
Time Period ◽  
Specific Igg ◽  
Antibody Levels ◽  
Over Time ◽  
Specific Igg Antibodies

More knowledge regarding persistence of antibody response to SARS-CoV-2 infections in the general population with mild symptoms is needed. We measured and compared levels of SARS-CoV-2 spike- and nucleocapsid-specific IgG-antibodies in serum samples from 145 laboratory-confirmed COVID-19 cases and 324 non-cases. The IgG-antibody levels against the spike protein in cases were stable over the time-period studied (14 to 256 days), while antibody levels against the nucleocapsid protein decreased over time.

scholarly journals Formation of humoral and cellular immunity to measles vaccine in adults

2020 ◽  
Vol 10 (1) ◽  
pp. 137-144
Author(s):  
A. P. Toptygina ◽  
Yu. Yu. Andreev ◽  
M. A. Smerdova ◽  
A. Yu. Zetkin ◽  
T. G. Klykova
Keyword(s):  
Immune Response ◽  
Cellular Immunity ◽  
Igg Antibodies ◽  
Humoral And Cellular Immunity ◽  
Measles Antibodies ◽  
Iga Antibodies ◽  
Measles Vaccination ◽  
Specific Igg ◽  
Cellular Immune ◽  
Specific Igg Antibodies

Despite adherence to the policy of mass measles vaccination in the majority of countries, this infection still remains far from being fully eradicated. Measles outbreaks are reported worldwide, when the vast majority of cases are recorded in subjects of 18—35 years of age. Studies on assessing measles IgG antibody level in different regions of Russia reveal increased percentage of measles seronegative subjects among young adults. Current study was aimed at investigating formation of humoral and cellular immunity after measles vaccination in seronegative adults aged 18 to 30 years old. There were enrolled 50 measles seronegative healthy volunteers aged 18 to 30 years old. Level of anti-measles IgM and IgG antibodies was measured by ELISA (Vector-Best, Russia). Subclasses of measles specific IgG antibodies were analyzed by ELISA, by replacing IgG conjugate for IgG1, IgG2, IgG3, IgG4 conjugates, whereas measles specific IgA antibodies were estimated by ELISA with IgA conjugate (Polygnost, Russia) at a concentration of 1 μg/ml. Antibody avidity was assessed by ELISA (Euroimmun, Germany). Cell-mediated measles immunity was estimated by CD107a surface expression on CD8hi T cell subset stimulated by measles virus-derived antigens. A specific cellular response to measles antigens before vaccination was detected in 50% of examined subjects, whereas 40% samples showed no signs of cellular immune response, with 10% of remaining cases described as equivocal. It was found that 6 weeks after vaccination all vaccinated subjects developed measles specific IgG antibodies at protective level reaching 1.33 (0.85—1.82) IU/ml [Me (LQ—UQ)]. Anti-measles IgA antibodies were of 0.655 (0.423—1.208) IU/ml [Me (LQ—UQ)]. However, no measles specific IgM antibodies were detected 6 weeks after vaccination. In addition, primary type of immune response (dominant low-avidity anti-measles antibodies IgG3 subclass) to measles vaccination was observed in 24 out of 50 subjects, whereas 26 subjects developed secondary type of immune response (high-avidity anti-measles antibodies dominated by IgG1 subclass). A measles specific cellular immune response was observed in 47 of the 50 examined subjects, and in 3 volunteers it was equivocal. Further analysis revealed a cohort of subjects who were not vaccinated against measles (18 subjects), although 60% of them provided medical record on previous dual measles vaccination occurred in childhood. Another cohort consisted of subjects who had medical record of measles vaccination in childhood (32 subjects), but lost protective measles antibodies produced by plasma cells (23 subjects), and memory T cells (3 subjects), or measles antibodies and memory B cells (6 subjects) over time. Such pattern evidences that measles-specific cellular and humoral arms immune responses were developed and maintained independently of each other.

scholarly journals Engineered ACE2 receptor traps potently neutralize SARS-CoV-2

2020 ◽  
Author(s):  
Anum Glasgow ◽  
Jeff Glasgow ◽  
Daniel Limonta ◽  
Paige Solomon ◽  
Irene Lui ◽  
...  
Keyword(s):  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Surface Display ◽  
Random Mutagenesis ◽  
Yeast Surface Display ◽  
Host Cells ◽  
Spike Protein ◽  
Receptor Protein ◽  
Yeast Surface ◽  
Flexible Protein

AbstractAn essential mechanism for SARS-CoV-1 and -2 infection begins with the viral spike protein binding to the human receptor protein angiotensin-converting enzyme II (ACE2). Here we describe a stepwise engineering approach to generate a set of affinity optimized, enzymatically inactivated ACE2 variants that potently block SARS-CoV-2 infection of cells. These optimized receptor traps tightly bind the receptor binding domain (RBD) of the viral spike protein and prevent entry into host cells. We first computationally designed the ACE2-RBD interface using a two-stage flexible protein backbone design process that improved affinity for the RBD by up to 12-fold. These designed receptor variants were affinity matured an additional 14-fold by random mutagenesis and selection using yeast surface display. The highest affinity variant contained seven amino acid changes and bound to the RBD 170-fold more tightly than wild-type ACE2. With the addition of the natural ACE2 collectrin domain and fusion to a human Fc domain for increased stabilization and avidity, the most optimal ACE2 receptor traps neutralized SARS-CoV-2 pseudotyped lentivirus and authentic SARS-CoV-2 virus with half-maximal inhibitory concentrations (IC50) in the 10-100 ng/ml range. Engineered ACE2 receptor traps offer a promising route to fighting infections by SARS-CoV-2 and other ACE2-utilizing coronaviruses, with the key advantage that viral resistance would also likely impair viral entry. Moreover, such traps can be pre-designed for viruses with known entry receptors for faster therapeutic response without the need for neutralizing antibodies isolated or generated from convalescent patients.

scholarly journals Study of the immunogenicity of recombinant protein consisting of multiple epitopes of porcine epidemic diarrhea virus highly expressed in Sf9 cells

2020 ◽  
Author(s):  
Yangkun Liu ◽  
Xiaomin Hu ◽  
Nannan Zhang ◽  
Na Li ◽  
Zhihan Guan ◽  
...  
Keyword(s):  
Porcine Epidemic Diarrhea Virus ◽  
Neutralizing Antibodies ◽  
Sf9 Cells ◽  
Igg Antibodies ◽  
Diarrhea Virus ◽  
Copy Gene ◽  
Specific Igg ◽  
Porcine Epidemic Diarrhea ◽  
High Level ◽  
Specific Igg Antibodies

Abstract Background Current inactivated and attenuated vaccines can not provide complete protection, resulting in the ongoing epidemic of porcine epidemic diarrhea virus (PEDV), which has caused significant economic losses in the swine industry worldwide. To develop an alternative efficient and economical vaccine, a fusion protein named S1CD containing multiple neutralizing epitopes of PEDV was designed and expressed in Sf9 cells. The expression yield was optimized by production of baculoviral constructs harboring multiple S1CD-expressing cassettes, and the immunogenicity of the purified protein was evaluated. Results The results showed that high-level expression of the S1CD fusion protein was achieved by multi-copy gene co-expression. The recombinant virus carrying three copies of S1CD gene under the control of p10 promoter showed the highest expression level, with a yield of 462 mg/L, which is about 2.6 or 3.5 fold that of the recombinant viruses carrying only one copy. BALB/c mice were subcutaneously immunized with purified S1CD protein three times at 2 week intervals. After immunization, S1CD protein could induce the mice produce high level of specific IgG antibodies and neutralizing antibodies. Conclusion Fusion S1CD protein consisting of multiple epitopes of porcine epidemic diarrhea virus was highly expressed by multi-copy gene co-expression. Moreover, it stimulated mice to produce high level of specific IgG antibodies and neutralizing antibodies. The S1CD protein expressed in this study could be used as a putative economic and efficient subunit vaccine against PEDV infection.

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