CYTOKINES AS POTENTIAL VACCINE ADJUVANTS

There is a compelling clinical need for adjuvants suitable for human u se to enhance the efficacy of vaccines in the prevention of life-threa tening infection. Candidate populations for such vaccine-adjuvant stra tegies include normal individuals at the two extremes of life, as well as the ever increasing population of immunocompromised individuals. I n addition, adjuvants that would increase the efficiency of vaccinatio n with such vaccines as those directed against hepatitis B and Strepto coccus pneumoniae would have an even greater general use. Cytokines, a s natural peptides intimately involved in the normal immune response, have great appeal as potential adjuvants. An increasing body of work u tilizing recombinant versions of interleukin-1, -2, -3, -6, -12, gamma -interferon, tumor necrosis factor, and granulocyte-monocyte-colony st imulating factor has shown that cytokines do have vaccine adjuvant act ivity. However, in order to optimize adjuvant effect and minimize syst emic toxicity, strategies in which the cytokine is fused to the antige n, or the cytokine is presented within liposomes or microspheres appea r 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 t o be accomplished in order to optimize the pharmacokinetics of cytokin e administration as well as its side effect profile.