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Comparative Immunology
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The way in which immunoglobulin molecules are coded for by light and heavy chain genes and the structures of the V, J, and C gene segments are conserved throughout the vertebrates. Nevertheless there are major differences among species in the organization of these immunoglobulin gene segments. For example, sharks and other elasmobranchs have clustered immunoglobulin genes where one V, D, J segment is linked to its own constant segment thus; VDJC-VDJC-VDJC-VDJC-VDJC-There are more than 500 of these VDJC clusters and each cluster is about 16 kilobases in size. This arrangement is different from that in teleost fish which have a mammalian type of arrangement with multiple Vh genes arranged thus;V-V-V-V-V-V-V-D-D-J-J-J-J-C-The low molecular weight immunoglobulin of lungfish, amphibians, reptiles, and birds is called immunoglobulin Y. Like the immunoglobulins of mammals, IgYconsists of two heavy and two light chains. The heavy chains, called upsilon (v) chains, usually consist of one variable and four constant domains and the complete molecule has a molecular weight of about 180 kDa. However, a truncated isoform that has only two constant domains is also found. This isoform has a molecular weight of about 120 kDa. Some other vertebrates such as ducks and geese, turtles and the lungfish have both full-sized and truncated IgY. Others such as chickens have only full-sized molecules while some turtles produce only truncated molecules. The truncated isoform of IgY is produced as a result of an alternative splicing of heavy chain mRNA. Its correct name is therefore IgY(AFc). Because this molecule lacks a Fc region, it Lacks the capacity to initiate the usual immunoglobulin effector functions such as complement activation and FcR binding. Its function is unclear. Similar truncated immunoglobulins have also been found to occur in some fish [IgM(AFc)], some turtles and in the quokka (Setonix brachyurus), a marsupial.
New anti-pseudomonal agents for cystic fibrosis- still needed in the era of small molecule CFTR modulators?
Published in Expert Opinion on Pharmacotherapy, 2018
Active immunization for P. aeruginosa in CF patients has proved frustrating and disappointing and despite many attempts, no such approaches are currently recommended [52]. Several approaches to passive immunization may however hold promise: immunoglobulin Y derived from the yolks of P. aeruginosa-exposed hens’ eggs is being administered as a gargle in a multicenter European trial (clinicaltrials.gov NCT01455675). This agent, used as a preventative strategy has recently been reported as effective in a murine model [53]. Kalobios have reported safety of a monoclonal antibody against PcrV, a component of the type III secretion system (MabKB001-A) [54]; although a single IV dose did not lead to changes in bacterial load, there were supportive reductions in sputum inflammatory markers. A follow on trial failed its primary outcome of time to next antibiotic course but showed an intriguing, statistically significant drop in the sputum inflammatory marker, IL-8 [55]. Panobacumab, a human monoclonal anti-LPS antibody, was reported as safe in phase 2a clinical trial in non-CF patients [56]. As there is currently so much focus on this area, it is hoped that the potential of the approach will be determined in the near future.
Scorpion envenomation: a deadly illness requiring an effective therapy
Published in Toxin Reviews, 2021
Faez Amokrane Nait Mohamed, Fatima Laraba-Djebari
A less expensive alternative to rAb, immunizing hens to obtain specific antibodies (IgY) from egg yolk, has been shown to be useful at the experimental therapeutic level (Thalley and Carroll 1990, Carroll et al.1992, Trinh and Trinh 2005, Alvarez et al.2015, Gopalakrishnakone et al.2015, Sifi et al.2018). The IgY technology was approved by the Swiss Government Federal Office as an alternative method aimed to improve animal welfare, after that the European Center for the Validation of Alternative Methods (ECVAM) workshop strongly recommended that IgY be used as an alternative to mammalian antibodies (Schade et al.1996). It was reported that immunized hens were able to produce the same amount of anti-venom as one horse per year (Araújo et al.2010). Functional characteristics of the IgY are homologous to mammalian IgG, including their specific role in secondary immune responses. Immunoglobulin Y is transferred from chicken blood to the egg through processes that take approximately 5 days. The amount of IgY in the yolk is proportional to the immunoglobulin concentration in the chicken serum (Schade et al.2005). It has been reported that anti-T. caripitensis IgY was able to neutralize 2 LD50 of T. caripitensis venom (97.8 mg of IgY neutralized 1 mg of T. caripitensis venom; Alvarez et al.2013). Interestingly, western blot analysis showed that IgY antibodies against T. caripitensis venom essentially recognized proteins with relative molecular weights of 31–24, 8.5, and 3.5 kDa, being the low molecular weight polypeptides of medical importance (Borges et al.2006, Petricevich 2010). More recently, an efficient and purified IgY antivenom against Aah scorpion venom was characterized by its ability to escape from mammalian complement recognition, making them an attractive alternative to equine antivenoms (Sifi et al.2018). The high amount of antivenom and the low maintenance cost make the production of IgY an attractive alternative to developing large stocks of antivenom for specific therapeutic applications against scorpion envenomation; however clinical trials are needed to test their tolerability and safety. On the other hand, experimental nanobodies (Nbs) produced in hyperimmunized camels have been also tested to neutralize Androctonus australis hector venom (Abderrazek et al.2009). The bispecific NbF12–10 was more efficient against scorpion envenoming in preclinical studies than classic fabotherapy. NbF12–10 was designed against both AahI and AahII toxins (Hmila et al.2010). Hmila et al. (2012) found that, following intravenous injection of 85 µg of NbF12–10, all mice were protected after a subcutaneous injection of 1 LD50 of Aah venom. However, in-vivo screening of radiolabeled nanobodies and F(ab’)2 fragments revealed that the nanobody-based molecules were cleared from the blood faster than the F(ab’)2 antivenom due to the lower molecular mass of nanobodies (Hmila et al.2012).