RESUMO
Plasmodium vivax Merozoite Surface Protein-9 (PvMSP-9) is a malaria vaccine candidate naturally immunogenic in humans and able to induce high antibody titers in animals when delivered as a recombinant protein. Recently, we identified the sequence EAAPENAEPVHENA (PvMSP9E795-A808) as the main linear B-cell epitope in naturally exposed individuals. However, the potential of PvMSP9E795-A808 as an immunogen in experimental animal models remained unexplored. Here we assess the immunogenicity of PvMSP9E795-A808 using synthetic peptides. The peptides tested in BALB/c mice include two repeats of the sequence EAAPENAEPVHENA tested alone (peptide RII), or linked to an autologous (PvMSP9 peptide pL; pLRII) or heterologous (p2 tetanus toxin universal T cell epitope; TTRII) T cell epitope. Immune responses were evaluated by ELISA, FLUOROSPOT, and indirect immunofluorescence. We show that all of the peptide constructs tested were immunogenic eliciting specific IgG antibodies at different levels, with a prevalence of IgG1 and IgG2. Animals immunized with synthetic peptides containing T cell epitopes (pLRII or TTRII) had more efficient antibody responses that resulted in higher antibody titers able to recognize the native protein by immunofluorescence. Relevantly, the frequency of IFN-γ secreting SFC elicited by immunization with TTRII synthetic peptide was comparable to that reported to the PvMSP9-Nt recombinant protein. Taken together, our study indicates that PvMSP9E795-A808 is highly immunogenic in mice and further studies to evaluate its value as promising vaccine target are warranted. Moreover, our study supports the critical role of CD4 T cell epitopes to enhance humoral responses induced by subunit based vaccines.
Assuntos
Epitopos de Linfócito B/imunologia , Imunogenicidade da Vacina , Vacinas Antimaláricas/imunologia , Proteínas de Membrana/imunologia , Peptídeos/síntese química , Proteínas de Protozoários/imunologia , Animais , Anticorpos Antiprotozoários/imunologia , Formação de Anticorpos , Ensaio de Imunoadsorção Enzimática , Feminino , Imunoglobulina G/imunologia , Vacinas Antimaláricas/genética , Malária Vivax/prevenção & controle , Proteínas de Membrana/genética , Camundongos Endogâmicos BALB C , Peptídeos/imunologia , Plasmodium vivax , Proteínas de Protozoários/genética , Proteínas Recombinantes/síntese química , Proteínas Recombinantes/imunologia , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
The present article describes a series of 21 N-(aryl)-2-thiophen-2-ylacetamides, which were synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis, and the activity expressed as the minimum inhibitory concentration (MIC) in mug/mL. The compounds 2, 3, 7, 8, 11, 12, 15, 16, and 20 exhibited activity between 25 and 100 microg/mL and could be a good start point to find new lead compounds in the fight against multidrug resistant tuberculosis.