Vaccination with the recombinant Brucella outer membrane protein 31 or a derived 27-amino-acid synthetic peptide elicits a CD4+ T helper 1 response that protects against Brucella melitensis infection

CASSATARO J,; ESTEIN S,; PASKEVICH K,; C A, VELIKOVSKI; DE LA BARRERA S,; BOWDEN RA,; CARLOS ALBERTO FOSSATI; GIAMBARTOLOMEI GH,

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Año: 2005 vol. 73 p. 8079 - 8088

0019-9567

The immunogenicity and protective efficacy of the recombinant 31-kDa outer membrane protein fromBrucella melitensis (rOmp31), administered with incomplete Freund?s adjuvant, were evaluated in mice. Immunizationof BALB/c mice with rOmp31 conferred protection against B. ovis and B. melitensis infection.rOmp31 induced a vigorous immunoglobulin G (IgG) response, with higher IgG1 than IgG2 titers. In addition,spleen cells from rOmp31-immunized mice produced interleukin 2 (IL-2) and gamma interferon, but not IL-10or IL-4, after in vitro stimulation with rOmp31, suggesting the induction of a T helper 1 (Th1) response.Splenocytes from rOmp31-vaccinated animals also induced a specific cytotoxic-T-lymphocyte activity, whichled to the in vitro lysis of Brucella-infected macrophages. In vitro T-cell subset depletion indicated that rOmp31immunization elicited specific CD4
T cells that secrete IL-2 and gamma interferon, while CD8
T cellsinduced cytotoxic-T-lymphocyte activity. In vivo depletion of T-cell subsets showed that the rOmp31-elicitedprotection against B. melitensis infection is mediated by CD4
T cells while the contribution of CD8
T cellsmay be limited. We then evaluated the immunogenicity and protective efficacy of a known exposed region fromOmp31 on the Brucella membrane, a peptide that contains amino acids 48 to 74 of Omp31. Immunization withthe synthetic peptide in adjuvant did not elicit a specific humoral response but elicited a Th1 responsemediated by CD4
T cells. The peptide in adjuvant induced levels of protection similar to those induced byrOmp31 against B. melitensis but less protection than was induced by rOmp31 against B. ovis. Our resultsindicate that rOmp31 could be a useful candidate for the development of subunit vaccines against B. melitensisand B. ovis.