ADJUVANT ACTIVITY OF MURAMYL DIPEPTIDE DERIVATIVES TO ENHANCE IMMUNOGENICITY OF A HANTAVIRUS-INACTIVATED VACCINE

The adjuvant effect of two lipophilic derivatives of muramyl dipeptide (MDP), B30-MDP and MDP-Lys(L18), on the ability of an inactivated vac cine of B-I virus (B-l vaccine) to induce immune response against Hant avirus causing hemorrhagic fever with renal syndrome (HFRS) was examin ed, When mice were immunized subcutaneously (s.c.) twice at 2-week int ervals with B-I vaccine admixed with or without 100 mu g mouse(-1) of B30-MDP (B-1/B30-MDP) or MDP-Lys(L18) [B-1/MDP-Lys(L18)], mice immuniz ed with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed Significantly h igher indirect fluorescent antibody (IFA) titers against HFRS virus th an mice immunized with B-I vaccine alone, Both mice treated with B-1/B 30-MDP and B-1/MDP-Lys(L18) also exhibited significantly higher neutra lizing antibody titers against HFRS virus than mice immunized with B-I ,vaccine alone during 3-9 weeks after-the primary immunization. The e valuation of antibody-producing cells by enzyme-linked immunospot (ELI SPOT) assay on week 4 revealed that both MDP derivatives,es enhanced t he number of HFRS virus-specific IgG1 and IgM antibody-producing cells . Furthermore, mice treated with B-1/B30-MDP as well as B-1/MDP-Lys(L1 8) showed a higher level of Th-2 type cytokines, IL-4 and IL-6, in ser a than mice treated with B-l alone. In an in-vitro analysis of T lymph ocyte proliferation to baculovirus-expressed recombinant nucleocapsid pi protein (rNP) of Hantaan 76-118 sa strain, the splenocytes of mice treated with B-1/B30-MDP and B-1/MDP-Lys(L18) on week 4 showed a Signi ficantly higher proliferating activity than those treated with B-1 vac cine alone, In addition when mice were immunized once with B-l vaccine admixed with or without B30-MDP and MDP-Lys(L18) and followed by intr afootpad (i.f.) injection of B-I vaccine on day 7, mice immunized with B-1/B30-MDP and B-1/MDP-Lys(LIS) induced a higher delayed-type hypers ensitivity (DTH) reaction than mice immunized with B-I vaccine alone, These results suggest that B30-MDP and MDP-Lys(L18) are useful immunoa djuvants to enhance the ability of inactivated B-l vaccine to induce a humoral and cellular response to HFRS virus, (C) 1997 Elsevier Scienc e Ltd, All rights reserved.