       Document 0594
 DOCN  M9620594
 TI    Protective vaccination with promastigote surface antigen 2 from
       Leishmania major is mediated by a TH1 type of immune response.
 DT    9602
 AU    Handman E; Symons FM; Baldwin TM; Curtis JM; Scheerlinck JP; Walter and
       Eliza Hall Institute of Medical Research, Victoria,; Australia.
 SO    Infect Immun. 1995 Nov;63(11):4261-7. Unique Identifier : AIDSLINE
       MED/96029715
 AB    Leishmania major promastigote surface antigen-2 complex (PSA-2)
       comprises a family of three similar but distinct polypeptides. The three
       PSA-2 polypeptides were purified from cultured promastigotes by a
       combination of detergent phase separation and monoclonal antibody
       affinity chromatography. Intraperitoneal vaccination of C3H/He mice with
       PSA-2 with Corynebacterium parvum as an adjuvant resulted in complete
       protection from lesion development after challenge infection with
       virulent L. major. Significant protection was also obtained in the
       genetically susceptible BALB/cH-2k and BALB/c mice. One of the PSA-2
       genes was cloned and expressed in both Escherichia coli and Leishmania
       mexicana promastigotes. Vaccination with the recombinant PSA-2 purified
       from E. coli did not confer protection, in contrast to the L.
       mexicana-derived recombinant PSA-2, which provided excellent protection.
       CD4+ T cells isolated from the spleens of vaccinated mice produced large
       amounts of gamma interferon but no detectable interleukin 4 upon
       stimulation with PSA-2 in vitro. Limiting dilution analysis showed a
       marked increase in the precursor frequency of PSA-2-specific gamma
       interferon-secreting CD4+ T cells. No substantial change in precursor
       frequency was observed for interleukin 4-secreting T cells in the
       vaccinated mice. A CD4+ PSA-2 specific T-cell line generated from
       splenocytes of a vaccinated mouse produces a cytokine pattern consistent
       with a TH1 phenotype. Intravenous injection of this line into naive mice
       reduced significantly the parasite burden upon challenge infection.
       Taken together, the data suggest that vaccination with PSA-2 induces a
       TH1 type of immune response which protects mice from L. major infection.
       Moreover, a single recombinant PSA-2 polypeptide derived from a genomic
       clone can also vaccinate, provided that the structural form of the
       antigen is near native.
 DE    Animal  Antibodies, Protozoan/BIOSYNTHESIS  Antigens,
       Protozoan/*IMMUNOLOGY  Antigens, Surface/*IMMUNOLOGY  Leishmania
       major/*IMMUNOLOGY  Leishmaniasis, Cutaneous/*PREVENTION & CONTROL  Mice
       Mice, Inbred BALB C  Mice, Inbred C3H  Protozoan Vaccines/*IMMUNOLOGY
       Support, Non-U.S. Gov't  Th1 Cells/*IMMUNOLOGY  Vaccination  Vaccines,
       Synthetic  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

