Abstract
BackgroundControl of currently circulating re-assorted low-pathogenicity avian influenza (LPAI) H9N2 is a major concern for both animal and human health. Thus, an improved LPAI H9N2 vaccination strategy is needed to induce complete immunity in chickens against LPAI H9N2 virus strains. Cytokines play a crucial role in mounting both the type and extent of an immune response generated following infection with a pathogen or after vaccination. To improve the efficacy of inactivated LPAI H9N2 vaccine, attenuated Salmonella enterica serovar Typhimurium was used for oral co-administration of chicken interferon-α (chIFN-α) and chicken interleukin-18 (chIL-18) as natural immunomodulators.ResultsOral co-administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18, prior to vaccination with inactivated AI H9N2 vaccine, modulated the immune response of chickens against the vaccine antigen through enhanced humoral and Th1-biased cell-mediated immunity, compared to chickens that received single administration of S. enterica serovar Typhimurium expressing either chIFN-α or chIL-18. To further test the protective efficacy of this improved vaccination regimen, immunized chickens were intra-tracheally challenged with a high dose of LPAI H9N2 virus. Combined administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18 showed markedly enhanced protection compared to single administration of the construct, as determined by mortality, clinical severity, and feed and water intake. This enhancement of protective immunity was further confirmed by reduced rectal shedding and replication of AIV H9N2 in different tissues of challenged chickens.ConclusionsOur results indicate the value of combined administration of chIFN-α and chIL-18 using a Salmonella vaccine strain to generate an effective immunization strategy in chickens against LPAI H9N2.
Highlights
Control of currently circulating re-assorted low-pathogenicity avian influenza (LPAI) H9N2 is a major concern for both animal and human health
Combined oral administration of χ8501/chicken interferon-α (chIFN-α) and χ8501/chicken interleukin-18 (chIL-18) showed significantly enhanced Hemagglutination inhibition (HI) antibody titers in the sera of AI-vaccinated chickens at both doses, compared to single administration of S. enterica serova Typhimurium expressing chIL18 or chIFN-α. These results indicate that oral co-administration of S. enterica serovar Typhimurium expressing chIL-18 and chIFN-α produces enhanced humoral immune responses against AI vaccine
Average feed and water intake improved more when the chickens received χ8501/chIFN-α and χ8501/chIL-18 either singly or in combination (109 and 1011 cfu) before vaccination with better result from the later. These results indicate that oral co-administration of S. enterica serovar Typhimurium expressing chIFN-a and chIL-18 prior to AI vaccination could markedly reduce mortality and alleviate clinical signs induced by infection with Avian influenza viruses (AIV) H9N2
Summary
Control of currently circulating re-assorted low-pathogenicity avian influenza (LPAI) H9N2 is a major concern for both animal and human health. Cytokines play a crucial role in mounting both the type and extent of an immune response generated following infection with a pathogen or after vaccination. Recent studies of avian cytokines identified a number of cytokines having immunomodulatory and antiviral properties against several viral infections. Recent studies showed that recombinant chIL-18 has immunomodulatory and anti-viral properties against AIV [10]. Both chIFN-α and chIL-18 may have great value for use either singly or in combination in disease prevention strategies in chickens. The practical mass administration of chicken cytokines to control poultry diseases is limited due to the absence of a cost effective delivery system
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