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 respiratory tract. The delay in their development has been due in part to a lack of understanding of the mucosal and neonatal immune systems. This work reviews recent advances in the understanding of the cells and molecules that mediate immunity, describing the importance of different T helper populations in determining the success of vaccination strategies. These advances have allowed the rational design of novel vaccine adjuvants and delivery systems that can selectively induce immunity at different anatomical sites mediated by distinct T cell populations. Five functional classes of adjuvant are 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. Comparisons are made between the chemical structures of bacterial toxins and non-toxic derivatives that retain adjuvanticity. The concept of DNA immunization is introduced and the advantages and disadvantages of this novel approach are discussed. The specific problems relating to neonatal immunization are explored with particular reference to the functional immaturity of the neonatal immune system and interference by maternal antibody. Finally, recent work suggesting that there is no intrinsic barrier to designing effective neonatal vaccines deliverable by the mucosal route is discussed.