Black dots are the data points and the red curves are the fitting of the data to a 11 interaction model. antibodies capable of multivalent binding to the target antigen. When administered orally toC. jejuni-infected two-day aged chicks, the pentabodies significantly reducedC. jejunicolonization in the ceca.In vitro, the motility of the bacteria was also reduced in the presence of the flagella-specific pentabodies, suggesting the mechanism of action is through either direct interference with flagellar motility or IRAK inhibitor 1 antibody-mediated aggregation. Fluorescent microscopy and Western blot analyses revealed IRAK inhibitor 1 specific binding of the anti-flagella pentabodies to theC. jejuniflagellin. == Introduction == Campylobacter jejuni, a Gram unfavorable bacterium, is currently one of the most prevalent foodborne pathogens and the leading cause of bacterial gastroenteritis in humans worldwide[1]. In North America, campylobacteriosis outnumbers the reported cases of illnesses caused bySalmonella, Shigella, ListeriaandEscherichia colicombined[2][4]. Despite relatively moderate diarrheal illness,C. jejuniinfection has been associated with severe long-term complications, including: Guillain-Barr Syndrome[5][7], reactive arthritis and inflammatory bowel disease[8],[9]. It is estimated that between 5080% of human campylobacteriosis cases can be attributed to consumption of contaminated chicken, and therefore meat from broiler chickens is considered the primary vector for transmitting the pathogen to humans[10][12]. Reduction ofC. jejunilevels in poultry decreases the incidence ofCampylobacter-associated gastroenteritis[12],[13]. Various intervention strategies targeting different stages of poultry meat production are currently under investigation. To date the most accepted strategies work by preventingCampylobacterspp. from entering the flock through installation of hygiene barriers and travel screens, use of high quality water, reduction of slaughter age, and discontinuation of thinning practices[12],[14][17]. However, the susceptibility of chickens to contamination byC. jejuniand its ubiquity in the environment have negatively impacted the success of biosecurity-based approaches, highlighting the need for alternative approaches by which the bacterial infection can be controlled or eliminated[3],[18],[19]. Antibiotics such as fluoroquinolones and macrolides have been approved for the control ofCampylobacterspp. in both poultry and humans. However, their prolonged use in humans and animals has led to a rapid increase of resistant strains in many countries around the world and their use is no longer recommended in animal feed stocks[20][22]. Application ofCampylobacter-specific lytic bacteriophages has been proposed as an alternative strategy. A reduction in cecalC. jejunilevels of 0.55 log10CFU/g has been reported when bacteriophages were administered to chickens as feed-additives or veterinary drugs[23][25]. Development of resistance, however, is considered to be a potential drawback of phage therapy and has been reported following phage treatment in several studies[26],[27]. In addition, obtaining a phage cocktail that would kill allC. jejunistrains is usually unlikely. Bacteriocins, which are proteinaceous substances produced by bacteria that inhibit growth, have also been extensively studied. Addition of bacteriocins to poultry drinking water completely eliminated the pathogen in 90% of cases or reduced its levels by 106-fold or more[28]. Other biological reagents such as probiotics[29],[30]and herb bioactive compounds[31],[32]have also been used as food or water additives and have been shown to STAT2 reduceCampylobacterloads in chickens. The bactericidal effects of probiotic strains such as lactic acid bacteria againstC. jejunihave been attributed to the production of organic acids and bacteriocins or bacteriocin-like substances[29],[33]. Medium chain fatty acids such as caprylic acid and monoacylglycerols are alternatives to antibiotics that have been used as feed and water additives to control or eliminateCampylobacterloads in chickens[34][36]. However, despite the reported efficacies none of these compounds have been widely adopted in the field due to inconsistency or lack of data on efficacy, safety, toxicity, scale-up production and purification, IRAK inhibitor 1 and the development of resistance[12](reviewed in[14]). Furthermore, other methods of intervention such as using vaccines[37][41], competitive exclusion[12],[14],[37],[42],[43]or producing genetically engineeredCampylobacter-resistant chickens[44]have had limited success in preventingC. jejunicolonization in chickens, and therefore, have not been commercialized. Antibodies were originally recognized as effective antimicrobial reagents by Behring and Kitasato in the early 1890s[45],[46]and since then, serum therapy became an effective strategy to combat many infectious diseases. The presence of specific antibodies in the serum or intestinal secretions has been associated with resistance of rabbits[47][49]and mice[49],[50]to colonization byC. jejuni. In young chickens (less than 23 weeks of age), the presence of maternal antibodies againstCampylobacterdelays the onset of colonization and reduces the rate of horizontal spread ofC. jejuniin the flock[19], suggesting that passive immunotherapy using anti-Campylobacterantibodies could be an attractive approach for interfering with bacterial colonization in chickens. Indeed, passive immunization with anti-flagella monoclonal antibodies has already been shown to reduceC. jejunicolonization in mice[51]. Similarly, the use of hyperimmunized anti-C. jejunirabbit serum.
