EFFECTIVE ADJUVANTS FOR THE INDUCTION OF ANTIGEN-SPECIFIC DELAYED-TYPE HYPERSENSITIVITY

Vaccines utilizing poorly immunogenic subunit antigens are dependent u pon adjuvants to drive the appropriate T cell responses. In an effort to determine the ability of several adjuvants to promote cell-mediated immunity (CMI), we assessed delayed-type hypersensitivity (DTH) in mi ce inoculated with heat-killed Listeria monocytogenes (HKLM) vaccines. The vaccines were formulated as oil-in-water emulsions containing one or more of the following bacterial-derived immunostimulators. MPL(R) immunostimulant, a monophosphoryl lipid A preparation synthetic trehal ose dicorynomycolate (TDCM) and Mycobacterium phlei cell wall skeleton (CWS). Oil-in-water emulsions containing HKLM without adjuvants did n ot induce DTH responsiveness in mice. The incorporation of TDCM, or MP L(R) plus TDCM and/or CWS to the formulation enabled the HKLM vaccine to stimulate CMI characterized by DTH responsiveness. Following antige n challenge the resulting increases in footpad thickness ranged from 1 5-20% and were comparable to the DTH driven by complete Freund's adjuv ant. Adjuvants composed of MPL/TDCM and MPL/TDCM/CWS induced responses equivalent to those measured in mice immunized with viable L. monocyt ogenes, and the responses remained at these levels for at least 2 mont hs. Furthermore, in vivo depletion of CD4+ T cells, but not CD8+ T cel ls, abrogated the induction and expression of DTH, indicating that the response is mediated by CD4+ T cells. (C) 1997 Elsevier Science Ltd.