PROTECTIVE VACCINATION WITH PROMASTIGOTE SURFACE-ANTIGEN-2 FROM LEISHMANIA-MAJOR IS MEDIATED BY A TH1 TYPE OF IMMUNE-RESPONSE
- Author(s)
- Handman, E; SYMONS, FM; Baldwin, TM; Curtis, JM; Scheerlinck, JPY;
- Details
- Publication Year 1995-11-01,Volume 63,Issue #11,Page 4261-4267
- Journal Title
- INFECTION AND IMMUNITY
- Publication Type
- Journal Article
- Abstract
- 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/c H-2(k) 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.
- Publisher
- AMER SOC MICROBIOLOGY
- Keywords
- MURINE CUTANEOUS LEISHMANIASIS; T-CELL EPITOPES; VISCERAL LEISHMANIASIS; POLYACRYLAMIDE GELS; ESCHERICHIA-COLI; SECRETING CD4+; BALB/C MICE; INFECTION; PROTEINS; AMAZONENSIS
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Creation Date: 1995-11-01 12:00:00