Aluminum salts have been widely used in vaccine formulations and, after their introduction more than 80 years ago, only few vaccine formulations using new adjuvants were developed in the last two decades. Recent advances in the understanding of how innate mechanisms influence the adaptive immunity opened up the possibility for the development of new adjuvants in a more rational design. The purpose of this review is to discuss the recent advances in this field regarding the attempts to determine the molecular basis and the general mechanisms underlying the development of new adjuvants, with particular emphasis on the activation of receptors of innate immune recognition. One can anticipate that the use of these novel adjuvants will also provide a window of opportunities for the development of new vaccines.

Uma linhagem mutante de células de rato-canguru (PtK2) com aumento de sensibilidade à luz ultravioleta (UV) foi isolada a partir de um sistema de seleção positiva. A caracterização desta linhagem indicou que tanto a síntese translesão como o reparo-excisão das lesões mais freqüentemente induzidas por UV, dímeros de pirimidina e (6-4) pirimidina-pirimidonas, encontram-se em níveis normais. No entanto, esta linhagem apresenta uma redução no nível de incisões logo após a indução das lesões, o que poderia representar um defeito no reparo preferencial de genes ativos. Alterações na proliferação celular, com uma fase S mais longa, também foram detectadas. Este fenótipo reforça a idéia de que mecanismos de controle do metabolismo celular, como ciclo celular, reparo, transcrição e morte celular, estão interligados.

Using a positive selection system for isolating DNA replication and repair related mutants, we isolated a clone from a rat kangaroo cell line (PtK2) that has increased sensitivity to UV light. Characterization of this clone indicated normal post-replication repair after UV irradiation, and normal removal rates of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts by excision repair. However, this cell line has decreased ability to make early incisions on damaged DNA, possibly indicating a defect in preferential repair of actively transcribed genes, and a slower cell proliferation rate, including a longer S-phase. This phenotype reinforces the present notion that control of key mechanisms in cell metabolism, such as cell cycle control, repair, transcription and cell death, can be linked.