Cytokines as Vaccine Adjuvants

Abstract

This paper describes the bacterial expression and purification of bioactive recombinant ovine interleukin-2 (rovIL-2), interleukin-la (rovlL-la) and tumour necrosis factor a. These purified proteins had specific activities in appropriate bioassays of 1x10^, 1 x lO' and 1x10^ U/mg, respectively. Recombinant ovIL-la was assessed as an immunological adjuvant for the sheep response to the model protein avidin. Wben delivered either intradermally or intramuscularly in conjunction with avidin in aluminium hydroxide the rovIL-la significantly enhanced the secondary humoral response. Doses of 1, 10 or 100 |ig per sheep enhanced the humoral response to a similar extent. Recombinant ovIL-ip had similar adjuvant activity in that it was demonstrated to significantly enhance the sheep humoral response to an experimental H. contortus antigen. This increase in specific antibody, however, did not correlate with enhanced protection against infection with third stage H. contortus larvae. In addition incorporation of rovIL-1 P into the formulation was shown not to alter the isotype profile of H. contortus antigen specific antibody.

A potent adjuvant effect of CD40 antibody attached to antigen

“…We and others have been attempting to take a rational approach to the design of immunological adjuvants; using knowledge of the workings of the immune system to tailor adjuvants with very speci®c properties and predicted modes of action which should produce low or no side effects. Such rationally designed adjuvants have included recombinant cytokines 23,24 and fusions with complement component C3d. 25 We have shown that CD40 antibodies in large, and thus impractical doses can mimic T-cell help for T-independent antigens when given invivowith antigen.…”

The use of recombinant ovine IL‐1β and TNF‐α as natural adjuvants and their physiological effects in vivo

“…Various cytokines have been shown to be eective immunological adjuvants in a variety of model systems, enhancing protection induced by bacterial, viral and parasitic antigens (reviewed by Lin et al 2 Heath and Playfair, 8 Nohria and Rubin, 9 Dong et al 10 and Heath 11 ). Various cytokines have been shown to be eective immunological adjuvants in a variety of model systems, enhancing protection induced by bacterial, viral and parasitic antigens (reviewed by Lin et al 2 Heath and Playfair, 8 Nohria and Rubin, 9 Dong et al 10 and Heath 11 ).…”

“…As an alternative to chemical adjuvants, the use of cytokines as natural adjuvants is attracting considerable interest. Various cytokines have been shown to be eective immunological adjuvants in a variety of model systems, enhancing protection induced by bacterial, viral and parasitic antigens (reviewed by Lin et al 2 Heath and Playfair, 8 Nohria and Rubin, 9 Dong et al 10 and Heath 11 ).…”

Flow Cytometric Analysis of Cellular Changes in Mice after Intradermal Inoculation with a Liposome–Iscom Adjuvanted Vaccine

“…Adjuvants increase the immunogenicity of antigens by provoking the innate immune system [ 11, 14], but beyond the general appreciation that adjuvants activate macrophages there is an incomplete understanding of adjuvant action. This is partly because of the heterogeneity in the chemical composition of adjuvants [ 28], and because most studies have focused predominantly on the end product of immunization, namely the humoral or cell‐mediated immunity elicited [ 3, 4, 17, 21, 29–36]. Nevertheless, the dependence on vaccines for disease control and the widespread use of adjuvants to ensure immunological responses requires a better understanding of adjuvant action.…”