(1849 - 1933)
Pedagogo y filósofo. De él diría Emilio Roig de Leuchsenrig, que fue "durante largo tiempo, por excelencia, guía y maestro de cubanía".
Biomedical Sciences
1997 | Study on the immune response to MEP carried by Epitopes of different HIV isolations in animal models
Main executives entity: Center for Biotechnology and Genetic Engineering
Main author: Carlos Antonio Duarte Cano
Summary: Searching for an immunogene able to generate neutralizing antibodies against several HIV-1stumps, it was developed the concept of Multi-Epitope Polypeptides (MEPs). After an initial trial with MEP TAB1, in which the validity of the concept was preliminarily proved, eight MEPs variants have been generated: TAB4, TAB5, TAB6, TAB7, TAB8, TAB9, TAB11 and TAB13. TAB4 contains the region V3 of gp120 of six HIV-1 isolations, fused to a fragment of 26 aa of human interleukin 2 (IL2h). TAB5, TAB6 and TAB11 also contain two epitopes for auxiliary T cells, placed in different positions and with different processing signs. TAB7 and TAB8 represent variants of TAB4, in which the gene was respectively duplicated and triplicated. TAB4 developed the best response in rabbits and mice, with high antibody titers against V3 peptides, and with neutralizing activity against more than a viral stump. Next, the amino terminal region of P64K protein of N. meningitides replaced the IL2h fragment. This new protein, called TAB9, maintained expression levels similar to TAB4, and induced equivalent levels of antibodies. TAB9 was also more immunogenic in mice than an equimolar mixture of V3 peptides conjugated to BSA and than TAB13 variant, which contains two V3 additional epitopes. There were evaluated different immunogenic doses, as well as different adjuvants, and there was an evident superiority of oleaginous adjuvants. A production process was developed under compatible conditions for use in human beings. Macaques immunized with TAB9 in Montanide ISA720 developed a potent humoral response against V3 peptides, and neutralizing activity against several stumps. It was characterized the reactivity of these antibodies against an extensive peptides panel. TAB9 protein in Montanide ISA720 is being evaluated in a Phase 1 trial in healthy volunteers.
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