Cytokines as potential vaccine adjuvants

Abstract

There is a compelling clinical need for adjuvants suitable for human use to enhance the efficacy of vaccines in the prevention of life-threatening infection. Candidate populations for such vaccine-adjuvant strategies include normal individuals at the two extremes of life, as well as the ever increasing population of immunocompromised individuals. In addition, adjuvants that would increase the efficiency of vaccination with such vaccines as those directed against hepatitis B and Streptococcus pneumoniae would have an even greater general use. Cytokines, as natural peptides intimately involved in the normal immune response, have great appeal as potential adjuvants. An increasing body of work utilizing recombinant versions of interleukin-1, -2, -3, -6, -12, gamma-interferon, tumor necrosis factor, and granulocyte-monocyte-colony stimulating factor has shown that cytokines do have vaccine adjuvant activity. However, in order to optimize adjuvant effect and minimize systemic toxicity, strategies in which the cytokine is fused to the antigen, or the cytokine is presented within liposomes or microspheres appear to be necessary to make this a practical approach suitable for human use. There is much promise in this approach, but there is much work to be accomplished in order to optimize the pharmacokinetics of cytokine administration as well as its side effect profile.

Adjuvant Action of MurineIL-2/IgPlasmid After Intramuscular Immunization With Indian HIV-1 Subtype C Recombinantenv.gp120 Construct

“…Cytokines as immune modulator proteins are secreted by a variety of cells, particularly those involved in the normal immune response, such as macrophages and T cells. A number of results published to date have clearly shown the co-stimulatory effects of cytokines with different kinds of vaccines, which were displayed in the modulation and improvement of immune response in immunized animals (22,20,24,28). Initial studies of cytokines as potential adjuvants focused on the action of IL-2, as this cytokine not only enhanced cellular immune responses such as induction of cytotoxic T cells, activation of natural killer (NK) and lymphokine activated killer (LAK) cells and the production of other cytokines by T cells (31,32) but also stimulated proliferation of activated B-lymphocytes and induced immunoglobulin secretion (10).…”

Vaccine adjuvants: Current challenges and future approaches

“…242 Less toxic adjuvants, such as alum, may also be less potent or ineffective at eliciting cell mediated immunity. 97,243,244 Good immunostimulatory vaccine adjuvants activate DCs to mature into APC and migrate to the draining lymph node, coincident with induction of the cytokine profile appropriate to the desired immune response mechanism (i.e., IFN-g, IL-2, and IL-12 for the Th1 response and IL-4, IL-5, and IL-6 for the Th2 response). Like adjuvants that target DCs, some immunostimulatory vaccine adjuvants also interact with TLR proteins.…”

“…Practical considerations such as stability and cost may preclude the widespread use of some otherwise potent protein adjuvants such as cytokines. 64,244 Thus, we can summarize the ideal vaccine adjuvant as one which selectively targets the antigen to the desired population of APCs, minimizes the amount of antigen required, induces the desired adaptive immune response while minimizing the innate immune response, is minimally toxic, low-cost, stable for long-term storage, and provides protective immunity in a single dose via a convenient delivery route.…”

Interleukin-2 Directly Induces Activation and Proliferation of Chicken T CellsIn Vivo

“…(1)(2)(3) These soluble proteins play a key role in coordinating immune responses by regulating the proliferation, differentiation, effector functions, and survival of the various cell populations that participate in the body's defense mechanism. (4,5) In particular, interleukin-2 (IL-2) has been studied extensively as a vaccine adjuvant in mammals because of its pleiotropic properties and pivotal role in activating T cell proliferation.…”