Co-administration of avian influenza virus H5 plasmid DNA with chicken IL-15 and IL-18 enhanced chickens immune responses

Lim, Kian-Lam; Jazayeri, Seyed Davoud; Yeap, Swee Keong; Alitheen, Noorjahan Banu Mohamed; Bejo, Mohd Hair; Ideris, Aini; Omar, Abdul Rahman

doi:10.1186/1746-6148-8-132

Cited by 30 publications

(13 citation statements)

References 38 publications

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“…IL18 can regulate both innate and adaptive immune responses through its effects on T cells (4,7,28), NK cells (29,30), macrophages (31), and DCs (32). Systemic administration of IL18 had little antitumor activity in several preclinical animal models (33).…”

Section: Discussionmentioning

confidence: 99%

Blocking NF-κB Is Essential for the Immunotherapeutic Effect of Recombinant IL18 in Pancreatic Cancer

Guo

Jiang

et al. 2016

Clinical Cancer Research

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Purpose: We sought to find new immune-based treatments for pancreatic cancer.Experimental Design: We detected IL18 expression in plasma and specimens from patients with pancreatic cancer. We then investigated whether IL18 had a therapeutic effect for pancreatic cancer in vitro and in vivo and any underlying mechanisms.Results: Higher plasma IL18 was associated with longer overall survival (OS), but higher IL18 in pancreatic cancer tissues was associated with shorter OS and increased invasion and metastasis. Recombinant IL18 alone had no antitumor effect in the syngeneic mice with orthotopically transplanted tumors and promoted tumors in immunocompromised mice; it also facilitated immune responses in vitro and in vivo by augmenting the activity of cytotoxic T cells and NK cells in peripheral blood and lymph nodes. However, IL18 promoted the proliferation and invasion of pancreatic cancer cells, in vitro and in vivo, through the NF-kB pathway. Nevertheless, by coadministrating IL18 with BAY11-7082, an NF-kB inhibitor, we were able to prevent the procancerous effects of IL18 and prolong the survival time of the mice.Conclusions: IL18 has both cancer-promoting and cancersuppressing functions. Although its single-agent treatment has no therapeutic effect on pancreatic cancer, when combined with the NF-kB pathway inhibitor, IL18 improved survival in a murine pancreatic cancer model. Our study implies the possibility of a combinational immunotherapy that uses IL18 and targets NF-kB pathway.

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Section: Discussionmentioning

confidence: 99%

Blocking NF-κB Is Essential for the Immunotherapeutic Effect of Recombinant IL18 in Pancreatic Cancer

Guo

Jiang

et al. 2016

Clinical Cancer Research

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“…IL-18 is a strong IFN-␥-inducing factor that enhances immune responses when used as an adjuvant. The concept of using IL-18 to boost immune responses after vaccination has been investigated for chicken vaccines (23,24,32,(36)(37)(38). Hung et al (21) described that the full-length and mature chicken IL-18 purified recombinant protein effectively enhanced cell-mediated and humoral immunity.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have shown that ChIL-18 is expressed in nonchicken-derived cells (21,32). However, there are no documents showing whether ChIL-18 plasmid expresses IL-18 in chicken cells.…”

Section: Discussionmentioning

confidence: 99%

A Eukaryotic Expression Plasmid Carrying Chicken Interleukin-18 Enhances the Response to Newcastle Disease Virus Vaccine

Wang¹,

Li²,

Zhang³

et al. 2014

Clin. Vaccine Immunol.

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Interleukin-18 (IL-18) is an important cytokine involved in innate and acquired immunity. In this study, we cloned the fulllength chicken IL-18 (ChIL-18) gene from specific-pathogen-free (SPF) chicken embryo spleen cells and provided evidence that the ChIL-18 gene in a recombinant plasmid was successfully expressed in chicken DT40 cells. ChIL-18 significantly enhanced gamma interferon (IFN-␥) mRNA expression in chicken splenocytes, which increased IFN-␥-induced nitric oxide (NO) synthesis by macrophages. The potential genetic adjuvant activity of the ChIL-18 plasmid was examined in chickens by coinjecting ChIL-18 plasmid and inactivated Newcastle disease virus (NDV) vaccine. ChIL-18 markedly elevated serum hemagglutination inhibition (HI) titers and anti-hemagglutinin-neuraminidase (anti-HN)-specific antibody levels, induced the secretion of both Th1-(IFN-␥) and Th2-(interleukin-4) type cytokines, promoted the proliferation of T and B lymphocytes, and increased the populations of CD3؉ T cells and their subsets, CD3 ؉ CD4 ؉ and CD3 ؉ CD8 ؉ T cells. Furthermore, a virus challenge revealed that ChIL-18 contributed to protection against Newcastle disease virus challenge. Taken together, our data indicate that the coadministration of ChIL-18 plasmid and NDV vaccine induces a strong immune response at both the humoral and cellular levels and that ChIL-18 is a novel immunoadjuvant suitable for NDV vaccination. N ewcastle disease (ND) is a serious avian disease that causes substantial economic loss and remains a major threat to the poultry industry (1, 2). Outbreaks of ND among poultry occur worldwide, and the pathogenic form of the virus is a disease listed in the World Organization for Animal Health (OIE) Terrestrial Animal Health Code and must be reported to the OIE (3), which results in severe trade limitations (4, 5). Currently, vaccination is the major tool for controlling infection by Newcastle disease virus (NDV). The NDV vaccine strains LaSota, B1, Mukteswar, and V4 are used widely in China. However, virulent NDV strains are still frequently isolated in vaccinated birds, indicating that NDV remains an ongoing threat to commercial flocks of birds (6). Therefore, it is necessary to develop more efficacious vaccines to prevent NDV infection.Many techniques have been developed to increase the immunogenicity of vaccines. Among these, cytokines are effective immunomodulators in animal models or in clinical testing (7-10). Among the large number of cytokines, interleukin-18 (IL-18) is a strong stimulator of T helper type 1 (Th1) responses and activates natural killer (NK) cells, stimulates the synthesis of other immunoactive cytokines from Th1 cells, monocytes, and NK cells, and synergizes with IL-12 in the maturation of Th1 cells and the suppression of IgE synthesis by B cells (11-13). Thus, IL-18 functions as an adjuvant (14, 15). However, depending on the cytokine environment, IL-18 may also promote Th2-type responses (16,17) and antibody formation (18).The isolation and characterization of chicken IL-18 (ChIL-18) ...

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“…Recombinant chicken IL-18 (chIL-18) protein also has the ability to act as a potent adjuvant when co-administered with cell-cultured Newcastle disease vaccine (14). Recently, it is reported that chicken IL-15 and IL-18 used as genetic adjuvants improve the immune responses induced from the AIV H5 DNA vaccination in chickens as evaluated by antibody production, T cell responses and cytokine production (15). However, the properties and practical application of chIL-18 remain largely uninvestigated as of yet.…”

Section: Introductionmentioning

confidence: 99%

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

Rahman

Uyangaa

2013

Immune Netw

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Interleukin-18 (IL-18) has been known to induce interferon-γ (IFN-γ) 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-γ 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.

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Co-administration of avian influenza virus H5 plasmid DNA with chicken IL-15 and IL-18 enhanced chickens immune responses

Cited by 30 publications

References 38 publications

Blocking NF-κB Is Essential for the Immunotherapeutic Effect of Recombinant IL18 in Pancreatic Cancer

Blocking NF-κB Is Essential for the Immunotherapeutic Effect of Recombinant IL18 in Pancreatic Cancer

A Eukaryotic Expression Plasmid Carrying Chicken Interleukin-18 Enhances the Response to Newcastle Disease Virus Vaccine

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

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