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Passive immunization as a method to protect birds has been tested for many years and shown to be effective. Its advantages over active vaccination include no use of partially virulent viruses, overcoming the gap in the level of protection at young age due to interference of maternal antibodies to raise self-immune response following active vaccination and the possible immunosuppressive effect of attenuated vaccine viruses. However, a major obstacle to its implementation is its relatively high cost which is dependent, among other things, mainly on two factors: the efficacy of antibody production, and the use of specific pathogen-free (SPF) birds for antibody production to avoid the possible transfer of pathogens from commercial layers. In this study we show efficient production of immunoglobulin Y (IgY) against four different pathogens simultaneously in the same egg, and treatment of the extracted IgY with formalin to negate the need for SPF birds. Formalin, a common registered sterilization compound in vaccine production, was shown not to interfere with the Fab specific antigen binding or Fc-complement activation of the antibody. Following injection of 1-day-old broilers with antibodies against infectious bursal disease virus, protective antibody levels were acquired for the entire period of sensitivity to this pathogen (35 days). Passive vaccination with formalin-sterilized IgY against multiple antigens extracted from one commercial egg may be a cost-effective and advantageous complementary or alternative to attenuated vaccines in poultry., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In the first 10-14 days of a chick's life, protection is conferred by maternal antibodies. Further broiler protection is achieved by active vaccination. However, the high level of maternal antibodies interferes with the induction of an effective immune response by vaccination at a young age. As a result, there is a gap between the reduction in protective maternal antibodies and elevation of self-produced antibodies following active vaccination. The major aim of this study was to test an approach consisting of passive and active vaccination to overcome this gap and to provide continuous resistance to infectious viral diseases during the broiler's growth period. Newcastle disease virus (NDV), which is one of the world's most prevalent infectious diseases of poultry, was tested as a model. Following subcutaneous injection of 18 hemagglutination-inhibiting (HI) units of anti-NDV immunoglobulin Y per 1-day-old chick, protective log2 antibody titers above 4 could be detected to at least 17 days of age. The combination of passive immunization on day 1 of age with attenuated live vaccination on day 10 led to high protective titers throughout the entire growth period, up to 41 days of age. Moreover, the HI titers in the group of birds immunized with the combined vaccination were significantly more homogeneous than those in the group vaccinated only with live virus. Thus, full protection against NDV of all broilers in flock during their entire growth period was achieved by a vaccination regime that combines passive immunization and live vaccination., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Passive vaccination is used to treat a wide range of infections and cancer. However, this approach has some limitations. An immune complex termed Y-complex was developed to intensify the effect of the passive vaccine. The complex is composed of a microbead that carries specific antibodies and an inducer. It enables targeting of pathogen or abnormal cells, and stimulation of a desired response by innate immune cells, depending on the inducer. The production and efficacy of Y-complex as a passive immune prophylaxis is demonstrated in this study by its use in treating cow mastitis. In an in vitro assay, Y-complex inhibited propagation and induced phagocytosis of bacteria. In challenge experiments, cows were inoculated through the udder with Escherichia coli or Streptococcus dysgalactiae. Following treatment with Y-complex, no bacteria were isolated in the milk and N-acetyl-ß-D-glucosaminidase activity had returned to normal levels. Thus the Y-complex approach can be used as an effective treatment for mastitis. Due to its modularity, this approach may serve as a treatment for a variety of disease agents., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Passive immunization with cross-species antibodies triggers the patient's immune response, thereby preventing repeated treatment. Mannosamine-biotin adduct (MBA) has been described as a masking agent for immunogenic reduction and here, the immunogenicity and biological activity of MBA-coated horse anti-viper venom (hsIgG) were compared to those of uncoated or PEGylated hsIgG. In in vitro tests, hsIgG binding was not affected by MBA conjugation. The immune response to hsIgG-MBA was about 8-fold and 32-fold lower than to PEG-coated and uncoated hsIgG, respectively. In vivo, hsIgG-MBA showed efficient venom-neutralization activity. We thus demonstrate the feasibility of using MBA as a masking agent for passive immunization with cross-species antibodies., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Antitumor activity of molecules and cells of the innate immune system has been reported. Here we propose a method for targeting preferred innate immune cells and magnifying their tumoricidal effect at the tumor microenvironment, by modular multiple-component complexes (termed TILTAN). As a model, micro-scale complexes were assembled carrying monoclonal anti-HER2 antibodies, lipopolysaccharide and/or mannose. The complexes showed high binding capacity to HER2-positive cancer cells in vitro, high induction of interleukin-1 RNA transcription by the activated monocytes and ability to mediate monocytes' attachment to HER2-positive cells. TILTAN treatment was found safe in in vivo testing and induced change in interleukin-1 RNA transcription in tumors xenografts. We thus present a new vision of targeting a desired innate immune response to the tumor microenvironment., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

A variety of protein-coating procedures are used to modify proteins' properties. The principle coating agent used is PEGylation, in which proteins are coated by conjunction to polyethylene glycol (PEG). In the present study, we describe a novel approach that makes use of small molecules with multifunctional groups as the protein-coating agent. The new coating molecule was produced by reacting two endogenous molecules, mannosamine and biotin, to form mannose-biotin adducts (MBA). hIgG was coated with MBA at various MBA/protein ratios. The immunogenicity of MBA-coated hIgG was tested in chickens. A dose-responsive effect of MBA/hIgG ratio on immune response suppression was detected, with an optimal masking effect at a 12:1 ratio. The immune response to MBA-coated hIgG was about eightfold lower than that to PEG-coated hIgG. MBA also increased antibody-antigen-binding affinity, and decreased recognition of the Fc domain of MBA-coated hIgG by Fc receptor and secondary antibodies. While the PEG molecule consists of inert repeating units of ethylene oxide with no additional functional group to allow for potentially desirable modifications, the MBA has several functional groups, including vicinal hydroxyls, which can easily be converted to active residues such as aldehydes or carboxyls. This may be of importance for developing passive immunizations or for achieving tolerance of the immune response to an immunogenic molecule or virus. In summary, we developed a new protein-coating molecule with the ability to mask foreign antigens and in the case of antibodies, to enhance activity.