Immune Netw.  2013 Feb;13(1):34-41. 10.4110/in.2013.13.1.34.

Modulation of Humoral and Cell-Mediated Immunity Against Avian Influenza and Newcastle Disease Vaccines by Oral Administration of Salmonella enterica Serovar Typhimurium Expressing Chicken Interleukin-18

• Rahman MM
• Uyangaa E
• Eo SK

• KMID: 2150769
• DOI: http://doi.org/10.4110/in.2013.13.1.34

Abstract

Interleukin-18 (IL-18) has been known to induce interferon-gamma (IFN-gamma) production and promote Th1 immunity. Although mammalian IL-18 has been characterized in great detail, the properties and application of chicken IL-18 remain largely uninvestigated as of yet. In this study, we evaluated the immunomodulatory properties of Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 (chIL-18) on immune responses induced by avian influenza (AI) and Newcastle disease (ND) vaccines. After oral administration of S. enterica serovar Typhimurium expressing chIL-18, chickens were vaccinated intramuscularly with the recommended dose of either inactivated AI H9N2 vaccine or ND (B1 strain) vaccine. Chickens receiving a primary vaccination were boosted using the same protocol 7 days later. Humoral and cell-mediated immune responses were evaluated in terms of HI antibody titers and proliferation and mRNA expression of IFN-gamma and IL-4 of peripheral blood mononuclear cells (PBMC) in response to specific antigen stimulation. According to our results, oral administration of S. enterica serovar Typhimurium expressing chIL-18 induced enhanced humoral and Th1-biased cell-mediated immunity against AI and ND vaccines, compared to that of chickens received S. enterica serovar Typhimurium harboring empty vector. Therefore, we conclude that our proposed vaccination regimen using inactivated AI and ND viruses along with oral administration of S. enterica serovar Typhimurium expressing chIL-18 may provide a novel approach in protecting chicken from currently circulating AI and ND virus strains.

Keyword

Avian influenza; Newcastle disease; Salmonella vaccine; Chicken interleukin-18; Immune modulation

MeSH Terms

Administration, Oral
Animals
Chickens
Immunity, Cellular
Influenza in Birds
Interferon-gamma
Interleukin-18
Interleukin-4
Newcastle Disease
RNA, Messenger
Salmonella
Salmonella enterica
Vaccination
Vaccines
Viruses
Interferon-gamma
Interleukin-18
Interleukin-4
RNA, Messenger
Vaccines

Figure

• 

  Figure 1 The serum hemagglutination inhibition (HI) antibody titers in chickens vaccinated intramuscularly with inactivated AIV H9N2 vaccine with or without oral administration of S. entericaserovar Typhimurium expressing chIL-18. (A) Diagram for vaccination schedule using S. entericaserovar Typhimurium expressing chIL-18. Groups of chickens were administered S. enterica serovar Typhimurium expressing chIL-18 (109 and 1011 cfu/chicken) and vaccinated with inactivated AIV H9N2 vaccine three days later. The vaccinations were performed by same protocol twice at 7-day intervals. (B) HI antibody titers in sera of vaccinated chickens. Serum samples collected from chickens of all groups 7 days after primary vaccination and 7 and 14 days after booster vaccination were subjected to HI testing. Data are expressed as reciprocal log2 of the geometric average and SEM of HI titers obtained from five chickens per group. ***p<0.001 compared to vehicle group treated with control bacteria.

• 

  Figure 2 The serum hemagglutination inhibition (HI) antibody titers in chickens vaccinated intramuscularly with inactivated NDV (B1 strain) vaccine with or without oral administration of S. entericaserovar Typhimurium expressing chIL18. Groups of chickens were administered S. entericaserovar Typhimurium expressing chIL-18 (109 and 1011 cfu/chicken) and vaccinated with inactivated NDV (B1 strain) vaccine three days later. The vaccinations were performed by same protocol twice at 7-day intervals. Serum samples collected from chickens of all groups 7 days after primary vaccination and 7 and 14 days after booster vaccination were subjected to HI testing. Data are expressed as reciprocal log2 of the geometric average and SEM of HI titers obtained from six chickens per group. ***p<0.001 compared to vehicle group treated with control bacteria.

• 

  Figure 3 Enhanced Th1-biased immunity in chickens vaccinated with inactivated AIV H9N2 vaccine following oral administration of S. entericaserovar Typhimurium expressing chIL-18. (A) AIV H9N2 antigen-specific proliferation of PBMCs. Groups of chickens were administered S. enterica serovar Typhimurium expressing chIL-18 (109 and 1011 cfu/chicken) and vaccinated with inactivated AIV H9N2 vaccine three days later. The vaccination was performed by same protocol twice at 7-day intervals. PBMCs (responders) were prepared from chickens 14 days after booster vaccination, and subsequently stimulated with autologous naïve PBMCs (stimulators) that had been pulsed with uv-inactivated AIV H9N2 antigen. Antigen-specific proliferation of PBMCs was assessed by measuring viable cell ATP bioluminescence following incubation for 72 h. (B) The expression of IFN-γ and IL-4 mRNA by PBMCs following stimulation with AIV H9N2 specific antigen. Total RNA was extracted from PBMCs stimulated with specific antigen for 72 h, and subjected to real-time qRT-PCR to determine the expression of IFN-γ and IL-4. Data show the average and SEM of IFN-γ and IL-4 expression obtained from five chickens per group, after normalized to GAPDH. ***p<0.001 compared to vehicle group treated with control bacteria.

• 

  Figure 4 Enhanced Th1-biased immunity in chickens vaccinated with inactivated NDV (B1 strain) vaccine following oral administration of S. entericaserovar Typhimurium expressing chIL-18. (A) NDV (B1 strain) antigen-specific proliferation of PBMCs. Groups of chickens were administered S. entericaserovar Typhimurium expressing chIL-18 (109 and 1011 cfu/chicken) and vaccinated with inactivated NDV (B1 strain) vaccine three days later. The vaccination was performed by same protocol twice at 7-day intervals. PBMCs (responders) were prepared from chickens 14 days after booster vaccination, and subsequently stimulated with autologous naïve PBMCs (stimulators) that had been pulsed with uv-inactivated NDV (B1 strain) antigen. Antigen-specific proliferation of PBMCs was assessed by measuring viable cell ATP bioluminescence following incubation for 72 h. (B) The expression of IFN-γ and IL-4 mRNA by PBMCs following stimulation with NDV (B1 strain) specific antigen. Total RNA was extracted from PBMCs stimulated with specific antigen for 72 h, and subjected to real-time qRT-PCR to determine the expression of IFN-γ and IL-4. Data show the average and SEM of IFN-γ and IL-4 expression obtained from six chickens per group, after normalized to GAPDH. ***p<0.001 compared to vehicle group treated with control bacteria.

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