Toll like receptors and cytokines as immunostimulatory adjuvants in poultry vaccines: current status and future trends

Abstract

In the face of reducing reliance on in-feed antibiotics, a greater emphasis has been placed on the development of vaccines. Adjuvants play important role in vaccine refinement. Apart from conventional adjuvants, others, like cytokines and toll-like receptors (TLR), have been evaluated experimentally. For example, Pam3CSK4, Polyinosinic-polycytidylic acid are used as immunostimulatory agents which upregulate the expression of type 1 IFNs against avian influenza. The use of TLR4 (lipopolysaccharide; LPS), TLR7 (Loxoribine) and TLR21 (CpG-ODN) agonists have shown good results when used as adjuvants with the avian influenza vaccine. The LPS (TLR4) was used as an adjuvant and liposome as intranasal antigen delivery system for Newcastle's disease (NDV) antigen, which induced significant increases in secretory IgA in tracheal lavage fluid and serum IgG levels. In a challenge study it provided 80% protection against virulent challenge. When resiquimod (TLR7) was used as an adjuvant with inactivated NDV, this potentiated the protective response to 100% against virulent NDV challenge, while protection was only 80% in the vaccine alone group. When 64CpG-plasmids (TLR21) were co-administered with inactivated AIV H5N2 vaccine in chickens, it led to a higher HI titre at two and four weeks of age, and provided 100% protection against virulent challenge of avian influenza. The TLR 3 agonist (poly I:C) showed good results against NDV and avian reovirus. Other TLR agonists and cytokines used against NDV include LPS, loxoribine, CpG-ODN and ChIFN-α, IFN- γ (with an in ovo vaccine). Immunostimulatory adjuvants like LPS, chicken TLR21, have been tried with Marek's disease vaccine, and TLR 5 agonist was used against Salmonella enteritidis and Eimeria tenella. Although the study of cytokines and TLRs in avian species is still in its infancy when compared to that of mammals, huge strides have been made in recent years. In this article, recent studies involving the assessment of immunostimulatory adjuvants in poultry are reviewed.