Developments in biologicals 

About: Developments in biologicals is an academic journal published by Karger Publishers. The journal publishes majorly in the area(s): Vaccination & Rabies. It has an ISSN identifier of 1424-6074. Over the lifetime, 724 publications have been published receiving 10950 citations.

Haemagglutination-inhibiting antibody to influenza virus.

Abstract: The results of the haemagglutination-inhibiting (HI) antibody test for influenza virus antibody in human sera closely match those produced by virus neutralization assays and are predictive of protection. On the basis of the data derived from 12 publications concerning healthy adults, we estimated the median HI titre protecting 50% of the vaccinees against the virus concerned at 28. This finding supports the current policy requiring vaccines to induce serum HI titres of > or = 40 to the vaccine viruses in the majority of the vaccinees. Unfortunately similar studies are scanty for the elderly, the group most at risk of influenza. There still remain many unsolved technical problems with the HI assay and we recommend that these problems be studied and the virus neutralization test as a predictor of resistance to influenza be assessed. Although the studies on this issue often give conflicting results, they generally show that HI antibody responses to influenza vaccination tend to diminish with increasing age, when health is often compromized. Advanced age in itself seems not to be an independent factor in this process. However, even in completely healthy elderly individuals the response to vaccination with an antigenically new virus may be strongly reduced compared with younger vaccinees.

Bacterial vaccines for fish--an update of the current situation worldwide

Abstract: During the last few years, the use of vaccines for disease prevention in aquaculture has expanded both with regard to the number of fish species and number of microbial diseases. According to the responses to a questionnaire received from 41 countries, vaccination is used in the commercial aquaculture of species like Atlantic salmon (Salmo salar), rainbow trout (Oncorhynchus mykiss), sea bass (Dicentrarchus labrax), sea bream (Sparus aurata), barramundi (Lates calcarifer), tilapia (Tilapia spp), turbot (Scophthalmus maximus L.), yellowtail (Seriola quinqueradiata), purplish and gold-striped amberjack (Seriola dumereli), striped jack (Pseudocaranx dentex) and channel catfish (Ictalurus punctatus). The range of bacterial infections for which vaccines are commercially available now comprises classical vibriosis (Listonella anguillarum, Vibrio ordalii), furunculosis (Aeromonas salmonicida subsp. salmonicida), cold-water vibriosis (Vibrio salmonicida), yersiniosis (Yersinia ruckeri), pasteurellosis (Photobacterium damselae supsp. piscicida), edwardsiellosis (Edwardsiella ictaluri), winter ulcer (Moritella viscosa), and streptococcosis/lactococcosis (Streptococcus iniae, Lactococcus garviae). Furthermore, experimental vaccines are used against diseases such as infection with Vibrio harveyi and Photobacterium damsela subsp. damsela in barramundi, piscirickettsiosis and bacterial kidney disease in salmonids, as well as infection with Flexibacter maritimus (now: Tenacibaculum maritimum) in turbot. There was good agreement between the information received from different sources in the same country. Most vaccines are licensed products, but some non-licensed vaccines are also used in commercial fish farms. Most bacterial vaccines are inactivated products and recombinant vaccine technology has so far been used to a very limited extent. Salmonid fish are usually immunised with multivalent vaccines by intraperitoneal injection. In marine fish species vaccination is generally performed by immersion, but use of injection vaccination is increasing, particularly in the Mediterranean region. Only limited use of orally administered fish vaccines is reported. In general, the effect of vaccination against bacterial infections is good. The best protection is obtained with injectable, adjuvanted vaccines. However, injection-site adverse reactions often occur when such products are used.

Equine vaccine for West Nile virus.

Abstract: To meet the urgent need of controlling West Nile virus (WNV) infection in the equine population, we have developed a killed WNV vaccine A dose titration study in horses was first conducted to evaluate serum neutralization antibody responses against WNV in these animals Horses were vaccinated intramuscularly twice with the test vaccine at low, medium and high dose, three weeks apart Serum samples were collected periodically and were measured for serum neutralizing antibody using a plaque reduction neutralization test Significant increases in serum neutralizing antibody were detected in all three dosage groups 14 days post the second vaccination Twelve months after the second vaccination, horses vaccinated with the medium dose of WNV vaccine and non-vaccinated control horses were experimentally challenged with WNV Nine out of 11 (818%) controls developed viraemia after challenge while only one out of 19 (53%) vaccinates had transient viraemia, representing a 94% preventable fraction In a separate study, the safety of the killed WNV vaccine was demonstrated under field conditions A total of 648 horses, including 32 pregnant mares, were enrolled in the study During the two weeks post vaccination period, no local or systemic adverse reactions were observed following 96% of the vaccinations administered while mild, transient injection site reactions were noted in a small number of horses These results indicate that the killed WNV vaccine developed by Fort Dodge Animal Health is safe and efficacious

De-immunization of therapeutic proteins by T-cell epitope modification.

Abstract: Many therapeutic proteins in clinical use have been shown to elicit antibody responses which in some cases have been linked to adverse events. Conventional animal models, although convenient, have rarely been predictive of immunogenicity in humans. New methods for predicting the potential immunogenicity of therapeutic proteins are needed. This treatise proposes a new approach which pairs in silico T-cell epitope analysis with in vitro studies. T-cell epitope mapping algorithms such as EpiMatrix can be used to evaluate a candidate therapeutic protein for T-helper epitopes, followed by confirmation of the T-helper epitopes using in vitro methods such as MHC binding assays and T-cell assays. Once these are identified, substitution of key amino acids in the T-cell epitopes may attenuate the immunogenicity of the protein, since modification of the amino acids in anchor position(s) can abrogate binding to human class II MHC molecules and presentation of the peptides, in the context of MHC, to T-helper cells. Following substitution of the key amino acids, immunogenicity of the modified protein can be evaluated in vitro. In parallel, the potential effect of the modifications on the structure of the protein can be evaluated using in silico modeling methods. This multi-step process has been termed DeFT for de-immunization of functional therapeutics. In this article we review the rationale for the approach, provide several retrospective examples that prove the approach in principle, and describe potential applications to therapeutic protein design. The demand for pre-clinical means of evaluating therapeutic proteins is expected to increase with the number of therapeutic proteins and monoclonal antibodies entering the pre-clinical pipeline. Examples provided offer some preliminary proof that the de-immunization approach may improve clinical outcomes.

Heterogeneity of recombinant antibodies: linking structure to function.

Abstract: Structural heterogeneity of recombinant IgG1 antibodies derives from variations in conserved as well as unique structural features. Common sources of heterogeneity include Fc glycosylation, partial heavy chain C-terminal Lys processing, Fc methionine oxidation, hinge-region cleavage, and the glycation of Lys residues. Aspartate residues that are isomerized to iso-aspartate were detected by cation exchange or hydrophobic interaction chromatography for trastuzumab and omalizumab, respectively. Unpaired cysteines were detected in omalizumab using Ellman's reagent, with the thiol-containing Fab resolved using hydrophobic interaction chromatography after papain digestion. Structural variations that cause chromatographic resolution may indicate the presence of a form with reduced potency.