The rational design of vaccine adjuvants for mucosal and neonatal immunization

There is an urgent requirement for neonatal vaccines that induce effective and long-lasting immune responses at the mucosal surfaces of the gut and re spiratory tract. The delay in their development has been due in part to a l ack of understanding of the mucosal and neonatal immune systems. This work reviews recent advances in the understanding of the cells and molecules tha t mediate immunity, describing the importance of different T helper populat ions in determining the success of vaccination strategies. These advances h ave allowed the rational design of novel vaccine adjuvants and delivery sys tems that can selectively induce immunity at different anatomical sites med iated by distinct T cell populations. Five functional classes of adjuvant a re described. These exploit mechanisms which a) create an antigen depot, b) preserve antigen conformation, c) direct antigen to specific immune cells, d) induce mucosal responses and e) induce cytotoxic T cell responses. Comp arisons are made between the chemical structures of bacterial toxins and no n-toxic derivatives that retain adjuvanticity. The concept of DNA immunizat ion is introduced and the advantages and disadvantages of this novel approa ch are discussed. The specific problems relating to neonatal immunization a re explored with particular reference to the functional immaturity of the n eonatal immune system and interference by maternal antibody. Finally, recen t work suggesting that there is no intrinsic barrier to designing effective neonatal vaccines deliverable by the mucosal route is discussed.