scholarly journals Equal Neutralization Potency of Antibodies Raised against Abrin Subunits

Antibodies ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 4
Author(s):  
Yoav Gal ◽  
Anita Sapoznikov ◽  
Reut Falach ◽  
Ohad Mazor ◽  
Ron Alcalay ◽  
...  

Abrin and ricin are potent AB toxins, which are considered biological threats. To date, there are no approved treatments against abrin or ricin intoxications. Previously, we showed that the administration of polyclonal anti-abrin antibodies to mice that were intranasally exposed to abrin, even very late post-exposure, conferred an exceedingly high-level of protection, while following ricin intoxication, similar treatment with anti-ricin antibodies resulted in negligible survival rates. To probe this unexpected difference in protection ability, we first examined whether the efficient anti-abrin-induced protection was due to neutralization of the A-subunit responsible for the catalytic effect, or of the B-subunit, which enables binding/internalization, by evaluating the protection conferred by antibodies directed against one of the two subunits. To this end, we generated and immunized rabbits with chimeric toxins containing a single abrin subunit, AabrinBricin in which abrin A-subunit was linked to ricin B-subunit, and AricinBabrin in which ricin A-subunit is linked to abrin B-subunit. Here, we show that antibodies raised against either AabrinBricin or AricinBabrin conferred exceptionally high protection levels to mice following intranasal exposure to a a lethal dose of abrin, suggesting that the high level of protection conferred by anti-abrin antibodies is not related to the neutralization of a particular subunit.

2012 ◽  
Vol 19 (5) ◽  
pp. 740-745 ◽  
Author(s):  
André A. Grassmann ◽  
Samuel R. Félix ◽  
Carolina Ximendes dos Santos ◽  
Marta G. Amaral ◽  
Amilton C. P. Seixas Neto ◽  
...  

ABSTRACTLeptospirosis, a worldwide zoonosis, lacks an effective, safe, and cross-protective vaccine. LipL32, the most abundant, immunogenic, and conserved surface lipoprotein present in all pathogenic species ofLeptospira, is a promising antigen candidate for a recombinant vaccine. However, several studies have reported a lack of protection when this protein is used as a subunit vaccine. In an attempt to enhance the immune response, we used LipL32 coupled to or coadministered with the B subunit of theEscherichia coliheat-labile enterotoxin (LTB) in a hamster model of leptospirosis. After homologous challenge with 5× the 50% lethal dose (LD50) ofLeptospira interrogans, animals vaccinated with LipL32 coadministered with LTB and LTB::LipL32 had significantly higher survival rates (P< 0.05) than animals from the control group. This is the first report of a protective immune response afforded by a subunit vaccine using LipL32 and represents an important contribution toward the development of improved leptospirosis vaccines.


1982 ◽  
Vol 186 (4) ◽  
pp. 572-574 ◽  
Author(s):  
E. S. Bogdanova ◽  
S. M. Mirkin ◽  
Zh. G. Shmerling
Keyword(s):  

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Omneya Attallah ◽  
Maha Sharkas

The rates of skin cancer (SC) are rising every year and becoming a critical health issue worldwide. SC’s early and accurate diagnosis is the key procedure to reduce these rates and improve survivability. However, the manual diagnosis is exhausting, complicated, expensive, prone to diagnostic error, and highly dependent on the dermatologist’s experience and abilities. Thus, there is a vital need to create automated dermatologist tools that are capable of accurately classifying SC subclasses. Recently, artificial intelligence (AI) techniques including machine learning (ML) and deep learning (DL) have verified the success of computer-assisted dermatologist tools in the automatic diagnosis and detection of SC diseases. Previous AI-based dermatologist tools are based on features which are either high-level features based on DL methods or low-level features based on handcrafted operations. Most of them were constructed for binary classification of SC. This study proposes an intelligent dermatologist tool to accurately diagnose multiple skin lesions automatically. This tool incorporates manifold radiomics features categories involving high-level features such as ResNet-50, DenseNet-201, and DarkNet-53 and low-level features including discrete wavelet transform (DWT) and local binary pattern (LBP). The results of the proposed intelligent tool prove that merging manifold features of different categories has a high influence on the classification accuracy. Moreover, these results are superior to those obtained by other related AI-based dermatologist tools. Therefore, the proposed intelligent tool can be used by dermatologists to help them in the accurate diagnosis of the SC subcategory. It can also overcome manual diagnosis limitations, reduce the rates of infection, and enhance survival rates.


1991 ◽  
Vol 11 (4) ◽  
pp. 1988-1995
Author(s):  
S I Yang ◽  
R L Lickteig ◽  
R Estes ◽  
K Rundell ◽  
G Walter ◽  
...  

Soluble, monomeric simian virus 40 (SV40) small-t antigen (small-t) was purified from bacteria and assayed for its ability to form complexes with protein phosphatase 2A (PP2A) and to modify its catalytic activity. Different forms of purified PP2A, composed of combinations of regulatory subunits (A and B) with a common catalytic subunit (C), were used. The forms used included free A and C subunits and AC and ABC complexes. Small-t associated with both the free A subunit and the AC form of PP2A, resulting in a shift in mobility during nondenaturing polyacrylamide gel electrophoresis. Small-t did not interact with the free C subunit or the ABC form. These data demonstrate that the primary interaction is between small-t and the A subunit and that the B subunit of PP2A blocks interaction of small-t with the AC form. The effect of small-t on phosphatase activity was determined by using several exogenous substrates, including myosin light chains phosphorylated by myosin light-chain kinase, myelin basic protein phosphorylated by microtubule-associated protein 2 kinase/ERK1, and histone H1 phosphorylated by protein kinase C. With the exception of histone H1, small-t inhibited the dephosphorylation of these substrates by the AC complex. With histone H1, a small stimulation of dephosphorylation by AC was observed. Small-t had no effect on the activities of free C or the ABC complex. A maximum of 50 to 75% inhibition was obtained, with half-maximal inhibition occurring at 10 to 20 nM small-t. The specific activity of the small-t/AC complex was similar to that of the ABC form of PP2A with myosin light chains or histone H1 as the substrate. These results suggested that small-t and the B subunit have similar qualitative and quantitative effects on PP2A enzyme activity. These data show that SV40 small-antigen binds to purified PP2A in vitro, through interaction with the A subunit, and that this interaction inhibits enzyme activity.


2019 ◽  
Vol 20 (11) ◽  
pp. 2682 ◽  
Author(s):  
Sneha Singh ◽  
Mohammad Suhail Akhter ◽  
Johannes Dodt ◽  
Peter Volkers ◽  
Andreas Reuter ◽  
...  

Coagulation factor XIII (FXIII) is a plasma-circulating heterotetrameric pro-transglutaminase complex that is composed of two catalytic FXIII-A and two protective/regulatory FXIII-B subunits. FXIII acts by forming covalent cross-links within a preformed fibrin clots to prevent its premature fibrinolysis. The FXIII-A subunit is known to have pleiotropic roles outside coagulation, but the FXIII-B subunit is a relatively unexplored entity, both structurally as well as functionally. Its discovered roles so far are limited to that of the carrier/regulatory protein of its partner FXIII-A subunit. In the present study, we have explored the co-presence of protein excipients in commercial FXIII plasma concentrate FibrogamminP by combination of protein purification and mass spectrometry-based verification. Complement factor H was one of the co-excipients observed in this analysis. This was followed by performing pull down assays from plasma in order to detect the putative novel interacting partners for the FXIII-B subunit. Complement system proteins, like complement C3 and complement C1q, were amongst the proteins that were pulled down. The only protein that was observed in both experimental set ups was alpha-2-macroglobulin, which might therefore be a putative interacting partner of the FXIII/FXIII-B subunit. Future functional investigations will be needed to understand the physiological significance of this association.


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