ABSTRACT
Brucella lumazine synthase (BLS) has been previously used with success as a delivery system for systemic immunization against murine cysticercosis. We herein determined the usefulness of BLS as a new antigen-delivery system and mucosal-adjuvant using KETc1, one of the peptides of the anti-cysticercosis vaccine. A protection of up to 98% was induced when KETc1 was used as a chimera fused to BLS. Used as adjuvant of KETc1, BLS also induced a high level of protection (79%), which did not significantly differ from that induced by the cholera toxin (74%). KETc1 and BLS administered separately also reduced the parasite load. KETc1 administered orally as a chimera, and to a lesser extent with BLS as adjuvant, elicited IgG and IgA specific antibodies, which were detectable both in fecal extracts and in sera, and increased B and CD4 activated cells. BLS-KETc1 also increased the levels of transcription of TNF-alpha, IL-2 and IFNgamma in Peyer's patches, and in spleen, only increased TNF-alpha was observed. Overall, these results showed that BLS can be used as both an antigen-carrier and as an adjuvant in the design of new oral subunit vaccines.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Antigens, Helminth/administration & dosage , Brucella/enzymology , Cysticercosis/prevention & control , Immunity, Mucosal , Multienzyme Complexes , Vaccines, Synthetic/administration & dosage , Administration, Oral , Animals , Antibodies, Helminth/blood , Antigens, Helminth/chemistry , Antigens, Helminth/genetics , Antigens, Helminth/immunology , Cysticercosis/immunology , Cytokines/metabolism , Female , Humans , Mice , Mice, Inbred BALB C , Peyer's Patches/immunology , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/immunology , Taenia/immunology , Vaccines, Synthetic/immunologyABSTRACT
Lumazine synthase from Brucella spp. (BLS) was evaluated as a protein carrier to improve antigen delivery of KETc1, one of the peptides of the anti-cysticercosis vaccine. KETc1 becomes antigenic, preserved its immunogenicity and its protective capacity when expressed as a recombinant chimeric protein using Brucella spp. lumazine synthase. KETc1 and BLS-KETc1 were not MHC H-2(d), H-2(k) nor H-2(b) haplotype-restricted albeit KETc1 is preferentially presented in the H-2(b) haplotype. These findings support that BLS is a potent new delivery system for the improvement of subunit vaccines.
Subject(s)
Antigens, Helminth/immunology , Brucella/enzymology , Multienzyme Complexes/immunology , Taenia solium/immunology , Vaccines, Synthetic/immunology , Animals , Female , Mice , Mice, Inbred BALB C , Recombinant Fusion Proteins/immunology , Tetanus Toxoid/immunologyABSTRACT
Trypanosoma cruzi Tc13 antigens belong to the trans-sialidase superfamily. Their sequences have been described only partially and, up to now, their physiological activity has not been elucidated. Here we present two new members of this family from the Tulahuén strain (Tc13 Tul) and the CL Brener clone (Tc13 CL), being the latter the first Tc13 sequence fully described. Alignment of all Tc13 sequences allowed us to define two sub-families that differ in the number of repeats and the presence or absence of the GPI addition site. Chromoblots demonstrate that Tc13 antigens are mainly located in chromosome III and its homologous. Pull down assays suggest that recombinant MBP-Tc13 Tul interacts with the second extracellular loop of the beta(1)-adrenergic receptor. This is the first evidence that a Tc13 antigen acts as a ligand interacting with a neurotransmitter receptor. These observations might add some light to the development of chagasic pathology.
