Resumen

MARCIANI, Dante J. Alzheimer’s disease: Toward the rational design of an effective vaccine. Rev Neuropsiquiatr [online]. 2015, vol.78, n.3, pp.140-152. ISSN 0034-8597.

The promising clinical results with the human monoclonal antibodies aducanumab and solanezumab targeting β-amyloidin Alzheimer’s disease treatment, confirm both the amyloid cascade hypothesis and protective natural immunity, while strengthening the immunotherapeutic approach. That aducanumab recognizes a conformational epitope formed byoligomers emphasizes the need for whole β-amyloid, not just its B-cell epitopes as have been the norm to avoid pro-inflammatory Th1-reactions.That truncated β-amyloid having N-terminal pyroglutamate is present only in diseased brain simples a new useful vaccine antigen. Another relevant antigenis the tau protein, which shows a close association and cooperativity with β-amyloid in exacerbating this disease. Hence, effective vaccines may be polyvalent, presenting to the immune system a number ofantigens relevant to induce an immune response to prevent or slowdown the onset of this disease. The presence of both B and T cell epitopes in the antigens, require a sole Th2 immunity to avert brain inflammation; a task that cannot beattain with adjuvants that under any conditions induce Th1 and/or Th17immunities. Hence, new vaccine adjuvants are need to safely induce Th2 whileinhibitingTh1 immunity, an objective that can be achieved with certain fucosylated glycans or triterpene glycosides, which apparently bind to the DC-SIGN lectin on dendritic cells polarizing the immune response toward Th2 immunity. Because the triterpene glycosides have the pharmacophore needed toco-stimulate T cells, they may ameliorate the T-cell anergy associated with immunosenescencea nd responsible for poor vaccine efficacy in the elderly population, a critical issue for an Alzheimer’s vaccine.

Palabras clave : Alzheimer’s; immunotherapy; vaccines; adjuvants; immunomodulators.

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