scholarly journals Orthogonal regulation of DNA nanostructure self-assembly and disassembly using antibodies

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Simona Ranallo ◽  
Daniela Sorrentino ◽  
Francesco Ricci

AbstractHere we report a rational strategy to orthogonally control assembly and disassembly of DNA-based nanostructures using specific IgG antibodies as molecular inputs. We first demonstrate that the binding of a specific antibody to a pair of antigen-conjugated split DNA input-strands induces their co-localization and reconstitution into a functional unit that is able to initiate a toehold strand displacement reaction. The effect is rapid and specific and can be extended to different antibodies with the expedient of changing the recognition elements attached to the two split DNA input-strands. Such an antibody-regulated DNA-based circuit has then been employed to control the assembly and disassembly of DNA tubular structures using specific antibodies as inputs. For example, we demonstrate that we can induce self-assembly and disassembly of two distinct DNA tubular structures by using DNA circuits controlled by two different IgG antibodies (anti-Dig and anti-DNP antibodies) in the same solution in an orthogonal way.

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Caitlin E. Mullarkey ◽  
Mark J. Bailey ◽  
Diana A. Golubeva ◽  
Gene S. Tan ◽  
Raffael Nachbagauer ◽  
...  

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.


2021 ◽  
Vol 15 (4) ◽  
pp. 161-167
Author(s):  
O. O. Obukhova ◽  
A. N. Trunov ◽  
O. M. Gorbenko ◽  
A. P. Shvayuk ◽  
T. I. Ryabichenko ◽  
...  

Aim. To determine the presence or absence of specific IgG antibodies against SARS-CoV-2 antigens in outpatient clinic staff and to compare clinical and immunological features from April to August 2020.Materials and Methods. The control group comprised 386 employees of the Novosibirsk City Clinical Polyclinic №13.The determination of IgG antibodies against SARS-CoV-2 antigens in blood serum was performed by using the ELISA method. A real time method of reverse transcription and polymerase chain reaction was used to extract RNA SARS-CoV-2 from nasopharyngeal and oropharyngeal swabs.Results. Specific IgG antibodies against SARS-CoV-2 antigens were detected in 32 (8.42%) employees of the polyclinic. Antibodies were not detected in 91.58% of employees. 9 members (28.12%) had clinical symptoms of varying degrees of disease severity in the group of employees with the presence of antibodies, 4 members of this group (12,51%) had bilateral community-acquired pneumonia with signs of COVID infection, another 5 members (15.61%) with antibodies had signs of ARVI of mild and moderate severity. RNA SARS-CoV-2 in the group of employees with the presence of antibodies and clinical implications was not detected in any case; 23 (71.88%) members with the presence of IgG-antibodies did not have clinical implications of the disease.Conclusion. The presence of specific antibodies against SARS-CoV-2 in employees with clinical implications of COVID-19 without detection of the RNA virus in the biological material is a retrospective confirmation of the etiology of the transferred infection. The detection of specific antibodies in persons who did not have clinical implications can serve as confirmation of the asymptomatic course of the transferred coronavirus infection.


Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1031
Author(s):  
Olivera Lijeskić ◽  
Ivana Klun ◽  
Marija Stamenov Djaković ◽  
Nenad Gligorić ◽  
Tijana Štajner ◽  
...  

Real-life data on the performance of vaccines against SARS-CoV-2 are still limited. We here present the rates of detection and levels of antibodies specific for the SARS-CoV-2 spike protein RBD (receptor binding domain) elicited by four vaccines available in Serbia, including BNT-162b2 (BioNTech/Pfizer), BBIBP-CorV (Sinopharm), Gam-COVID-Vac (Gamaleya Research Institute) and ChAdOx1-S (AstraZeneca), compared with those after documented COVID-19, at 6 weeks and 3 months post first vaccine dose or post-infection. Six weeks post first vaccine dose, specific IgG antibodies were detected in 100% of individuals fully vaccinated with BNT-162b2 (n = 100) and Gam-COVID-Vac (n = 12) and in 81.7% of BBIBP-CorV recipients (n = 148), while one dose of ChAdOx1-S (n = 24) induced specific antibodies in 75%. Antibody levels elicited by BNT-162b2 were higher, while those elicited by BBIBP-CorV were lower, than after SARS-CoV-2 infection. By 3 months post-vaccination, antibody levels decreased but remained ≥20-fold above the cut-off in BNT-162b2 but not in BBIBP-CorV recipients, when an additional 30% were seronegative. For all vaccines, antibody levels were higher in individuals with past COVID-19 than in naïve individuals. A total of twelve new infections occurred within the first 3 months post-vaccination, eight after the first dose of BNT-162b2 and ChAdOx1-S (one each) and BBIBP-CorV (six), and four after full vaccination with BBIBP-CorV, but none required hospitalization.


2021 ◽  
Author(s):  
Kevin John Selva ◽  
Samantha K Davis ◽  
Ebene R Haycroft ◽  
Wen Shi Lee ◽  
Ester Lopez ◽  
...  

Objectives SARS-CoV-2 can be transmitted by aerosols and the ocular surface may be an important route of transmission. Little is known about protective antibody responses to SARS-CoV-2 in tears after infection or vaccination. We analysed SARS-CoV-2 specific IgG and IgA responses in human tears after either COVID-19 infection or vaccination. Methods We recruited 16 subjects with COVID-19 infection an average of 7 months previously and 15 subjects before and 2 weeks after Comirnaty (Pfizer-BioNtech) vaccination. Plasma, saliva and basal tears were collected. Pre-pandemic plasma, saliva and basal tears from 11 individuals were included as healthy controls. Antibody responses to 5 SARS-CoV-2 antigens were measured via multiplex. Results IgG antibodies to Spike and Nucleoprotein were detected in tears, saliva and plasma from subjects with prior SARS-CoV-2 infection in comparison to uninfected controls. While RBD-specific antibodies were detected in plasma, minimal RBD-specific antibodies were detected in tears and saliva. In contrast, high levels of IgG antibodies to Spike and RBD, but not Nucleoprotein, were induced in tears, saliva and plasma of subjects receiving 2 doses of the Comirnaty vaccine. Increased levels of IgA1 and IgA2 antibodies to SARS-CoV-2 antigens were detected in plasma following infection or vaccination, but were unchanged in tears and saliva. Conclusion Both infection and vaccination induce SARS-CoV-2-specific IgG antibodies in tears. RBD-specific IgG antibodies in tears were induced by vaccination but were not present 7 months post-infection. This suggests neutralising antibodies may be low in the tears late following infection.


Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 516
Author(s):  
Shuyi Yang ◽  
Keith R. Jerome ◽  
Alexander L. Greninger ◽  
Joshua T. Schiffer ◽  
Ashish Goyal

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.


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