Efficacy of DNA Adenine Methylase Salmonella Vaccines in Livestock

Abstract

Intensive livestock production and management systems are associated with increased faecal-oral pathogen transmission which can contribute to a high prevalence of multiple Salmonella serovars in large dairy farms and feedlots. Outbreaks of salmonellosis in livestock often reflect a series of events that compromise host immunity and increase pathogen exposure. High risk groups in cattle include neonates and post partum cows (Anderson, et al., 2001; House, et al., 2001a; Fossler, et al., 2005a) and variation in susceptibility to salmonella infection has been observed in sheep entering feedlots according to property of origin, body condition, and time of year (Norris, et al., 1989a; Norris, et al., 1989b; Richards and Hyder, 1991; Kelly, 1995; Makin, 2011). The associated increase in the incidence of disease and contamination of livestock-derived food products imposes a significant risk to food safety via consumption of contaminated meat, milk, eggs and vegetables. The development and application of effective Salmonella vaccines offers a potential means of reducing industry associated losses and public health risks. Effective Salmonella vaccination therefore requires induction of protection against several Salmonella serovars and stimulation of both innate and acquired immune mechanisms. Vaccine prophylaxis is normally achieved through vaccinating animals several weeks prior to virulent pathogen exposure. This is not possible in neonates where exposure occurs at birth and in feedlots where livestock are sourced from diverse locations and vendors. Additionally, direct physical handling of livestock to administer vaccines contributes to stress and may lead to carcass damage. Conducting stressful procedures at feedlot induction when there is concurrent exposure to a diversity of pathogens contributes to an increased risk of disease. iii Traditional vaccination methods are labour intensive and associated with carcass damage and adverse reactions. Oral delivery of vaccines and medications via drinking water is a common practice in intensively managed poultry. Oral vaccine delivery via drinking water avoids the stress of additional handling and provides a means of rapidly vaccinating large numbers of animals. The efficacy of Salmonella vaccination is largely influenced by the diversity of Salmonella serovars encountered and the interval between immunisation and pathogen exposure, which may be short in field settings, e.g., following birth, during transport and following introduction into feedlots. The timing of virulent pathogen exposure may also have an impact on the safety of a Salmonella vaccine. It is imperative to develop livestock vaccines that are capable of safely eliciting potent states of cross-protective immunity against a diversity of serovars. This thesis examines the capacity of the dam S. Typhimurium vaccine (serogroup B) to elicit cross-protection against a virulent challenge in models of neonate and adult ruminant models of salmonellosis, as well as investigating in-water vaccine delivery. Cross-protective efficacy of the vaccine was evaluated against an emerging, clinically relevant, and multi-drug resistant strain of serovar Newport (serogroup C2-C3) that had been associated with clinical disease in calves and humans (CDC, 2002; Clark, 2004). Vaccinated calves challenged with S. Newport exhibited a significant attenuation of clinical disease and a concomitant reduction in S. Newport faecal shedding and colonisation of mesenteric lymph nodes and lungs compared to non-vaccinated control animals. The safety and efficacy of a S. Typhimurium dam vaccine in adult sheep was demonstrated via novel oral delivery in drinking water (ad libitum). The capacity of S. Typhimurium dam vaccine to be delivered in drinking water to protect livestock from virulent Salmonella challenge offers an effective, economical, stressor free Salmonella prophylaxis for intensive livestock production systems.