Recombinant vaccinia viruses expressing GP46/M-2 protect against Leishmania infection.
Leishmania is a genus of parasitic protozoa capable of causing a spectrum of human diseases. The GP46/M-2 membrane glycoprotein has been demonstrated in a murine model system to elicit a protective immune response against infection with Leishmania amazonensis; in highly susceptible BALB/c mice, immunization leads to significant protection against infection. In the present study, for induction of long-term immunological effects, two recombinant vaccinia viruses, derived from the wild type and attenuated variant 48-7 and expressing the GP46/M-2 protein, were constructed; to ensure safety, we used the attenuated vaccinia virus mutant (48-7) as a live vector. Susceptible BALB/c mice immunized with either GP46/M-2-recombinant vaccinia virus were significantly protected against infection with L. amazonensis; 45 to 76% of the animals were completely protected (sterile) against a challenge inoculum of 10(3) infective organisms. The protectively immunized animals demonstrated T- and B-cell-dependent immunological responses; both lymphokine responses as well as antibody responses and long-term memory are indicative of T-cell activation. This first report of the use of a recombinant vaccinia virus to induce protection against a Leishmania infection indicates that recombinant vaccinia viruses should be of value in the design of a safe and effective vaccine against this parasitic disease.
McMahon-Pratt
D
D
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06510.
Rodriguez
D
D
Rodriguez
J R
JR
Zhang
Y
Y
Manson
K
K
Bergman
C
C
Rivas
L
L
Rodriguez
J F
JF
Lohman
K L
KL
Ruddle
N H
NH
D000818:Animals; D005260:Female; D007894:Leishmania mexicana / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic; C066248:surface glycoprotein GP46-M-2, Leishmania