Resiquimod enhances mucosal and systemic immunity against avian infectious bronchitis virus vaccine in the chicken

Abstract

Adjuvant enhancing mucosal immune response is preferred in controlling many pathogens at the portal of entry. Earlier, we reported that a toll-like-receptor 7 (TLR7) agonist, resiquimod (R-848), stimulated the systemic immunity when adjuvanted with the inactivated Newcastle disease virus vaccine in the chicken. Here, we report the effect of R-848 when adjuvanted with live or inactivated avian infectious bronchitis virus (IBV) vaccines with special emphasis on mucosal immunity. Specific pathogen free (SPF) chicks (n = 60) were equally divided into six groups at two weeks of age and immunized with either inactivated or live IBV vaccine adjuvanted with or without R-848. Groups that received either PBS or R-848 served as control. A booster was given on 14 days post-immunization (dpi). R-848 enhanced the antigen specific humoral and cellular immune responses when co-administered with the vaccines as evidenced by an increase in the antibody titre in ELISA and stimulation index in lymphocyte transformation test (LTT) till 35 dpi and increased proportion of CD4 and CD8 T cells on 21 dpi in the flow cytometry. Interestingly, it potentiated the IgA responses in the tear and intestinal secretions when used with both live and inactivated IBV vaccines. The combination of IBV vaccine with R-848 significantly up-regulated the transforming growth factor beta 4 (TGFβ4) transcripts in the peripheral blood mononuclear cells (PBMCs) than that of the respective vaccine per se. An enhanced secretory IgA response is likely due to the up-regulation of TGFβ4, which is responsible for class switching to IgA. In conclusion, co-administration of R-848 with inactivated or live IBV vaccine enhanced the systemic as well as mucosal immune responses in the chicken.

Combination of TLR2 and TLR3 agonists derepress infectious bursal disease virus vaccine-induced immunosuppression in the chicken

“…Earlier, we reported the enhancement of antigen-specific humoral and cellular immune responses as well as protection against infection with the virulent Newcastle disease (ND) virus, when R-848, a TLR7 agonist was used with an inactivated ND vaccine in specific pathogen free (SPF) chickens 14 . Recently, we reported the enhancement of antigen-specific systemic and mucosal immune responses when R-848 was used with avian infectious bronchitis virus vaccines 15 , as well as the prophylactic potential of R-848 against infection with very virulent IBDV in SPF chickens 16 . Although a single TLR agonist is capable of inducing potent immune responses, a combination of TLR agonists might minimize the dose and side effects, mimic the natural infection and induce more balanced or desirable immune responses.…”

Antiviral response elicited against avian influenza virus infection following activation of toll-like receptor (TLR)7 signaling pathway is attributable to interleukin (IL)-1β production

“…resiquimod, imiquimod, gardiquimod and ioxoribine) [ 7 , 10 ]. In chickens, ssRNA can induce antibacterial effects against Salmonella Enteritidis [ 11 ] and antiviral effects against infectious bursal disease virus infection [ 12 , 13 ]. Recently, a study demonstrated that ssRNA upregulates mRNA expression of pro-inflammatory mediators including IL-1β and iNOS in chicken in vivo [ 14 ].…”

Avian Infectious Bronchitis Virus

“…However, there was no further increase in IgA level upon challenge, suggesting the significant role of neutralizing antibodies in reducing the potency of IBV infection at the time of challenge (Joiner et al 2007). In our lab, administration of resiquimod (R-848), a TLR-7 agonist with inactivated or live IBV vaccine increased the secretory IgA, which was mediated through the enhanced expression TGF-β4 in the chicken (Matoo et al 2018).…”